Comprehensive Physiology Wiley Online Library

Hepatic circulation

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Anatomy and Microcirculation
1.1 Origin and Distribution of Hepatic Blood Supply
1.2 Microcirculation
2 Blood Flows and Vascular Resistance
2.1 Sinusoidal Pressure
2.2 Relation Between Portal Flow and Liver Mass
2.3 Intrinsic Hepatic Arterial Flow Regulation
2.4 Extrinsic Hepatic Arterial Flow Regulation
3 Effects of Hepatic Blood Flow On Uptake of Substrates
3.1 Goresky Model
3.2 Equilibrium Model
3.3 Parallel‐Tube Model
3.4 Comparison of Models
3.5 Measurement of Hepatic Blood Flow by Uptake
4 Hepatic Blood Volume
4.1 Basic Principles, Terminology, and Normal Values
4.2 Hepatic Blood Volume in Perspective
4.3 Passive Changes in Hepatic Blood Volume
4.4 Active Capacitance Vessel Constriction
4.5 Reflex Control of Hepatic Venous Bed
4.6 Control of Cardiac Preload and Responses to Drugs
4.7 Other Complex Responses Involving Hepatic Venous Bed
4.8 Future Prospects
4.9 Hepatic Fluid Exchange
4.10 Sites of Filtration and Interstitial Fluid
4.11 Reabsorption of Filtered Fluid
4.12 Effects of Drugs on Fluid Exchange
4.13 Effects of Hepatic Nerve Stimulation on Fluid Exchange
Figure 1. Figure 1.

Diagram of hepatic vascular bed.

Figure 2. Figure 2.

Hepatic venous pressure profiles in basal state and at stable plateau phase during stimulation of hepatic nerves in cats. Portal venous pressure (PVP) and central venous pressure (CVP) were measured from stationary cannulas, whereas lobar venous profile was obtained by progressive withdrawal of lobar catheter. Pressures in portal vein and deep lobar venous pressures were not significantly different. Because pooled curves conceal steep contour of individual curves, data are recalculated in Fig. .

From Lautt et al.
Figure 3. Figure 3.

Hepatic venous pressure profiles recalculated from Fig. . Steepest portion of each profile curve was identified (RO), and pressure drop proximal and distal to this position was calculated. Most postsinusoidal resistance occurs across a short segment of veins, and hepatic nerves cause constriction at this same site. Pressure gradient from portal vein (PV) to 5 mm proximal to hepatic venous sphincter is on left and pressure gradient between a site 10 mm distal to sphincter and inferior vena cava (IVC) is on right.

From Lautt et al.
Figure 4. Figure 4.

Junctions of hepatic arterioles, portal venules, and sinusoids in the space of Mall showing postulated site of adenosine production. This adenosine concentration, which determines hepatic arteriolar tone, is regulated by production and washout into portal and hepatic arterial blood.

From Lautt et al.
Figure 5. Figure 5.

Arterial pressure, portal pressure, and hepatic arterial flow responses to stimulation of hepatic nerves in 1 cat and 1 dog. Note occurrence of autoregulatory escape of flow response in cat but not in dog.

From Greenway and Oshiro
Figure 6. Figure 6.

Left panel: relationship between liver blood flow and total hepatic clearance for drugs with various extraction rates. Arrows, normal physiological range of liver blood flow in humans; extraction values (E.R.) refer to normal flow of 1.5 liters/min. Right panel: relationship between extraction and liver blood flow for drugs with varying extraction values at a normal flow of 1.5 liters/min.

From Wilkinson and Shand
Figure 7. Figure 7.

Pressure‐volume relationship in hepatic venous bed (solid line). At transmural pressure P, hepatic blood volume or capacitance is C, [unstressed volume (U) plus stressed volume]. Slope of solid line, compliance. Venoconstriction (arrow) could result from a change in compliance with no change in unstressed volume (line 1), a change in unstressed volume with no change in compliance (line 2), or a combination of changes in both compliance and unstressed volume.

Figure 8. Figure 8.

Relationships between hepatic blood volume and intrahepatic pressure before, during, and after infusion of norepinephrine (NE), determined by varying portal flow (left panel) or by varying hepatic outflow pressure (right panel). Values are means ± SE; n = 9 for cats.

From Greenway et al.
Figure 9. Figure 9.

Effects of hepatic nerve stimulation on hepatic volume recorded by plethysmography in 1 dog.

From Greenway and Oshiro
Figure 10. Figure 10.

Mean (±; SE) changes in hepatic volume during hepatic nerve stimulation in 13 dogs and 15 cats. Mean control hepatic blood volume was 31 ml/100 g liver in dogs and 27 ml/100 g liver in cats.

From Greenway and Oshiro
Figure 11. Figure 11.

Frequency‐response curves for capacitance and resistance responses to hepatic nerve stimulation in cats.

From Green‐way et al.
Figure 12. Figure 12.

Effects of hepatic nerve stimulation in 1 cat before and after hemorrhage. Note that in spite of the change in stressed volume after hemorrhage, change in unstressed volume produced by nerve stimulation is almost unchanged. Thus effects of passive and active mobilization of blood volume are additive.

Figure 13. Figure 13.

Increases and decreases in splanchnic blood volume and flow in response to graded isolated changes in pressure in carotid sinus in 5 dogs. Points indicate response to increase or decrease in carotid sinus pressure from constant (windkessel‐controlled) systemic arterial pressure. Control pressure for each dog is listed.

From Brooksby and Donald
Figure 14. Figure 14.

Effects of intravenous epinephrine infusions on cardiac output and other variables in 10 cats (left panel) and effects of epinephrine predicted by computer model (right panel). Venous capacitance for cats is hepatic in ml · mmHg−1· 100 g−1 liver and that for model is total splanchnic in ml · mmHg−1 kg−1 body wt. Dashed lines,predicted responses if epinephrine did not reduce splanchnic venous capacitance (cardiac preload falls, and increase in cardiac output is markedly attenuated). *, P < 0.05; **, P < 0.01.

From Greenway and Innes
Figure 15. Figure 15.

Contribution of components of splanchnic reservoir when total blood volume was changed by hemorrhage or infusion of blood in cats.

From Greenway
Figure 16. Figure 16.

Changes in total hepatic volume and blood volume (mean ± SE) in 5 cats when hepatic venous pressure was increased to 9.4 mmHg for 60 min. Transsinusoidal fluid filtration was calculated by subtracting mean values of two curves.

From Greenway and Lautt
Figure 17. Figure 17.

Filtration rates induced by 3 levels of increased hepatic venous pressure during control periods (C) and during hepatic nerve stimulation at frequencies of 2, 4, and 8 Hz in 6 cats (means ± SE; *, P < 0.05; **, P < 0.01). Control portal pressure was 6.7 mmHg.

From Greenway


Figure 1.

Diagram of hepatic vascular bed.



Figure 2.

Hepatic venous pressure profiles in basal state and at stable plateau phase during stimulation of hepatic nerves in cats. Portal venous pressure (PVP) and central venous pressure (CVP) were measured from stationary cannulas, whereas lobar venous profile was obtained by progressive withdrawal of lobar catheter. Pressures in portal vein and deep lobar venous pressures were not significantly different. Because pooled curves conceal steep contour of individual curves, data are recalculated in Fig. .

From Lautt et al.


Figure 3.

Hepatic venous pressure profiles recalculated from Fig. . Steepest portion of each profile curve was identified (RO), and pressure drop proximal and distal to this position was calculated. Most postsinusoidal resistance occurs across a short segment of veins, and hepatic nerves cause constriction at this same site. Pressure gradient from portal vein (PV) to 5 mm proximal to hepatic venous sphincter is on left and pressure gradient between a site 10 mm distal to sphincter and inferior vena cava (IVC) is on right.

From Lautt et al.


Figure 4.

Junctions of hepatic arterioles, portal venules, and sinusoids in the space of Mall showing postulated site of adenosine production. This adenosine concentration, which determines hepatic arteriolar tone, is regulated by production and washout into portal and hepatic arterial blood.

From Lautt et al.


Figure 5.

Arterial pressure, portal pressure, and hepatic arterial flow responses to stimulation of hepatic nerves in 1 cat and 1 dog. Note occurrence of autoregulatory escape of flow response in cat but not in dog.

From Greenway and Oshiro


Figure 6.

Left panel: relationship between liver blood flow and total hepatic clearance for drugs with various extraction rates. Arrows, normal physiological range of liver blood flow in humans; extraction values (E.R.) refer to normal flow of 1.5 liters/min. Right panel: relationship between extraction and liver blood flow for drugs with varying extraction values at a normal flow of 1.5 liters/min.

From Wilkinson and Shand


Figure 7.

Pressure‐volume relationship in hepatic venous bed (solid line). At transmural pressure P, hepatic blood volume or capacitance is C, [unstressed volume (U) plus stressed volume]. Slope of solid line, compliance. Venoconstriction (arrow) could result from a change in compliance with no change in unstressed volume (line 1), a change in unstressed volume with no change in compliance (line 2), or a combination of changes in both compliance and unstressed volume.



Figure 8.

Relationships between hepatic blood volume and intrahepatic pressure before, during, and after infusion of norepinephrine (NE), determined by varying portal flow (left panel) or by varying hepatic outflow pressure (right panel). Values are means ± SE; n = 9 for cats.

From Greenway et al.


Figure 9.

Effects of hepatic nerve stimulation on hepatic volume recorded by plethysmography in 1 dog.

From Greenway and Oshiro


Figure 10.

Mean (±; SE) changes in hepatic volume during hepatic nerve stimulation in 13 dogs and 15 cats. Mean control hepatic blood volume was 31 ml/100 g liver in dogs and 27 ml/100 g liver in cats.

From Greenway and Oshiro


Figure 11.

Frequency‐response curves for capacitance and resistance responses to hepatic nerve stimulation in cats.

From Green‐way et al.


Figure 12.

Effects of hepatic nerve stimulation in 1 cat before and after hemorrhage. Note that in spite of the change in stressed volume after hemorrhage, change in unstressed volume produced by nerve stimulation is almost unchanged. Thus effects of passive and active mobilization of blood volume are additive.



Figure 13.

Increases and decreases in splanchnic blood volume and flow in response to graded isolated changes in pressure in carotid sinus in 5 dogs. Points indicate response to increase or decrease in carotid sinus pressure from constant (windkessel‐controlled) systemic arterial pressure. Control pressure for each dog is listed.

From Brooksby and Donald


Figure 14.

Effects of intravenous epinephrine infusions on cardiac output and other variables in 10 cats (left panel) and effects of epinephrine predicted by computer model (right panel). Venous capacitance for cats is hepatic in ml · mmHg−1· 100 g−1 liver and that for model is total splanchnic in ml · mmHg−1 kg−1 body wt. Dashed lines,predicted responses if epinephrine did not reduce splanchnic venous capacitance (cardiac preload falls, and increase in cardiac output is markedly attenuated). *, P < 0.05; **, P < 0.01.

From Greenway and Innes


Figure 15.

Contribution of components of splanchnic reservoir when total blood volume was changed by hemorrhage or infusion of blood in cats.

From Greenway


Figure 16.

Changes in total hepatic volume and blood volume (mean ± SE) in 5 cats when hepatic venous pressure was increased to 9.4 mmHg for 60 min. Transsinusoidal fluid filtration was calculated by subtracting mean values of two curves.

From Greenway and Lautt


Figure 17.

Filtration rates induced by 3 levels of increased hepatic venous pressure during control periods (C) and during hepatic nerve stimulation at frequencies of 2, 4, and 8 Hz in 6 cats (means ± SE; *, P < 0.05; **, P < 0.01). Control portal pressure was 6.7 mmHg.

From Greenway
References
 1. Aarseth, P. The effects of intraperitoneally and intravenously administered pentobarbitone anesthesia on pulmonary and splanchnic blood volumes in rats. Acta Physiol. Scand. 85: 270–276, 1972.
 2. Ahmad, A. B., P. N. Bennett, and M. Rowland. Models of hepatic drug clearance: discrimination between the “well stirred” and “parallel tube” models. J. Pharm. Pharmacol. 35: 219–224, 1983.
 3. Ahmad, A. B., P. N. Bennett, and M. Rowland. Influence of route of hepatic administration on drug availability. J. Pharmacol. Exp. Ther. 230: 718–725, 1984.
 4. Andreen, M., L. Irestedt, and B. Zetterström. The different responses of the hepatic arterial bed to hypovolemia and to halothane anesthesia. Acta Anaesthesiol. Scand. 21: 457–469, 1977.
 5. Appleton, C., M. Olajos E. Morkin, and S. Goldman. α1 adrenergic control of the venous circulation in intact dogs. J. Pharmacol. Exp. Ther. 233: 729–734, 1985.
 6. Ayers, A. B., B. N. Davies, and P. G. Withrington. Responses of the isolated, perfused human spleen to sympathetic nerve stimulation, catecholamines and polypeptides. Br. J. Pharmacol. 44: 17–30, 1972.
 7. Baker, K. J., and S. E. Bradley. Binding of sulfobromophthalein (BSP) sodium by plasma albumin. Its role in hepatic BSP extraction. J. Clin. Invest. 45: 281–287, 1996.
 8. Banaszak, E. F., W. J. Stekiel, R. A. Grace, and J. J. Smith. . Estimation of hepatic blood flow using a single injection dye clearance method. Am. J. Physiol. 198: 877–880, 1960.
 9. Barja, F., and R. Mathison. Adrenergic and peptidergic (substance P and vasoactive intestinal polypeptide) innervation of the rat portal vein. Blood Vessel 19: 263–272, 1982.
 10. Barrowman, J. A., M. A. Perry, P. R. Kvietys, and D. N. Granger. Exclusion phenomenon in the liver interstitium. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G410–G414, 1982.
 11. Bass, L. Current models of hepatic elimination. Gastroenterology 76: 1504–1505, 1979.
 12. Bass, L.. Flow dependence of first‐order uptake of substances by heterogeneous perfused organs. J. Theor. Biol. 86: 365–376, 1980.
 13. Bass, L. Models of hepatic drug elimination. J. Pharm. Sci. 72: 1229, 1983.
 14. Bass, L., S. Keiding, K. Winkler, and N. Tygstrup. Enzymatic elimination of substrates flowing through the intact liver. J. Theor. Biol. 61: 393–409, 1976.
 15. Bass, L. and P. J. Robinson. Effects of capillary heterogeneity on rates of steady uptake of substances by the intact liver. Microvasc. Res. 22: 43–57, 1981.
 16. Bass, L., P. Robinson, and A. J. Bracken. Hepatic elimination of flowing substrates: the distributed model. J. Theor. Biol. 72: 161–184, 1978.
 17. Bennett, T. D., C. L. MacAnespie, and C. F. Rothe. Active hepatic capacitance responses to neural and humoral stimuli in dogs. Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H1000–H1009, 1982.
 18. Bennett, T. D., and C. F. Rothe. Hepatic capacitance responses to changes in flow and hepatic venous pressure in dogs. Am. J. Physiol. 240 (Heart Circ. Physiol. 9): H18–H28, 1981.
 19. Bennett, T. D., C. R. Wyss, and A. M. Scher. Changes in vascular capacity in awake dogs in response to carotid sinus occlusion and administration of catecholamines. Circ. Res. 55: 440–453, 1984.
 20. Benoit, J. N., J. A. Barrowman, S. L. Harper, P. R. Kvietys, and D. N. Granger. Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G486–G493, 1984.
 21. Birtch, A. G., B. H. Casey, and R. M. Zakheim. Hepatic blood flow measured by the krypton‐85 clearance technique. Surgery St. Louis 62: 174–180, 1967.
 22. Blei, A. T., D. J. O'Reilly, J. Gottstein, W. W. Hauck and M. Zimmer. Distribution of portal blood flow in the liver of the rat: a microsphere study. J. Lab. Clin. Med. 104: 404–413, 1984.
 23. Blouin, A., R. P. Bolender, and E. R. Weibel. . Distribution of organelles and membranes between hepatocytes and non‐hepatocytes in the rat liver parenchyma. J. Cell Biol. 72: 441–455, 1977.
 24. Blumgart, L. H., A. M. Harper, D. P. Leiberman, and R. T. Mathie. Liver blood flow measurement with 85krypton clearance by portal venous and hepatic arterial routes of injection (Abstract). Br. J. Pharmacol. 60: 278P, 1977.
 25. Bollman, J. L. . The animal with an Eck fistula. Physiol. Rev. 41: 607–621, 1961.
 26. Bor, N. M., M. Alvur, M. Ercan, and C. F. Bekdik. Hepatic blood flow during rapid intravenous glucose tolerance test. Res. Exp. Med. 177: 159–165, 1980.
 27. Bornhof, C., P. O. Schwille, H. J. Beijer, and G. A. Charbon. Hemodynamic splanchnic and renal changes associated with administration of arginine‐hydrochloride in dogs. Res. Exp. Med. 177: 57–70, 1980.
 28. Borucki, L. J., D. Levenson, and N. K. Hollenberg. Cardiovascular responses to blockade of angiotensin and α‐adrenergic receptors. Am. J. Physiol. 235 (Renal Fluid Electrolyte Physiol. 4): F199–F202, 1978.
 29. Bradley, E. L. Measurement of hepatic blood flow in man. Surgery 75: 783–789, 1974.
 30. Bradley, S. E. The hepatic circulation. In: Handbook of Physiology. Circulation, edited by W. F. Hamilton. Bethesda, MD: Am. Physiol. Soc., 1963, sect. 2, vol. 2, chapt. 13, p. 1387–1438.
 31. Bradley, S. E., F. J. Ingelfinger, and G. P. Bradley. Hepatic circulation in cirrhosis of the liver. Circulation 5: 419–429, 1952.
 32. Branch, R. A., A. S. Nies, and D. G. Shand. The disposition of propranolol. VIII. General implications of the effects of liver blood flow on elimination from the perfused rat liver. Drug Metab. Dispos. 1: 687–690, 1973.
 33. Branch, R. A., D. G. Shand, and A. S. Nies. Increase in hepatic blood flow and D‐propranolol clearance by glucagon in the monkey. J. Pharm. Exp. Ther. 187: 581–587, 1973.
 34. Branch R. A., D. G. Shand, G. R. Wilkinson, and A. S. Nies. The reduction of lidocaine clearance by DL‐propranolol: an example of hemodynamic drug interaction. J. Pharm. Exp. Ther. 184: 515–519, 1973.
 35. Brauer, R. W. Liver circulation and function. Physiol. Rev. 43: 115–213, 1963.
 36. Brauer, R. W., R. J. Holloway, and G. F. Leong. Changes in liver function and structure due to experimental passive congestion under controlled hepatic vein pressures. Am. J. Physiol. 197: 681–692, 1959.
 37. Brauer, R. W., O. S. Shill, and J. S. Krebs. Studies concerning functional differences between liver regions supplied by the hepatic artery and by the portal vein. J. Clin. Invest. 38: 2202–2214, 1959.
 38. Braunwald E. J. Ross, R. L. Kahler, T. E. Gaffney, A. Goldblatt, and D. T. Mason. Reflex control of the systemic venous bed. Effects on venous tone of vasoactive drugs and of baroreceptor and chemoreceptor stimulation. Circ. Res. 12: 539–550, 1963.
 39. Bredfeldt, J. E., E. M. Riley, and R. J. Groszmann. Compensatory mechanism in response to an elevated hepatic oxygen consumption in chronic ethanol‐fed rats. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G507–G511, 1985.
 40. Britton, S. L., and D. E. Donald. Response of large hind‐limb veins of dog to aortic arch chemoreceptor stimulation. Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H1050–H1055, 1982.
 41. Brooksby G. A., and D. E. Donald. Dynamic changes in splanchnic blood flow find blood volume in dogs during activation of sympathetic nerves. Circ. Res. 29: 227–238, 1971.
 42. Brooksby, G. A., and D. E. Donald. Release of blood from the splanchnic circulation in dogs. Circ. Res. 31: 105–118, 1972.
 43. Brown, B. P., S. Anuras, and D. D. Heistad. Responsiveness of longitudinal and circular muscle layers in the portal vein. Am. J. Physiol. 242 (Gastrointest. Liver Physiol. 5): G498–G503, 1982.
 44. Brown, K. A., R. D. Okada, C. A. Boucher, J. A. Rothendler, H. W. Strauss, and G. H. Pohost. Exercise induced changes in hepatic blood volume measured during cardiac equilibrium cineangiography. J. Am. Coll. Cardiol. 2: 514–521, 1983.
 45. Browse, N. L., D. E. Donald, and J. T. Shepherd. Role of the veins in the carotid sinus reflex. Am. J. Physiol. 210: 1424–1434, 1966.
 46. Brunner, M. J., A. A. Shoukas, and C. L. MacAnespie. The effect of the carotid sinus baroreceptor reflex on blood flow and volume redistribution in the total systemic vascular bed of the dog. Circ. Res. 48: 274–285, 1981.
 47. Burchell, A. R., A. H. Moreno, W. F. Panke, and T. F. Nealon. Hepatic artery flow improvement after portocaval shunt: a single hemodynamic clinical correlate. Ann. Surg. 184: 289–300, 1976.
 48. Burczynski, F. J., and C. V. Greenway. Hepatic blood flow: accuracy of estimation from galactose clearances in cats. Can. J. Physiol. Pharmacol. 64: 1310–1315, 1986.
 49. Burczynski, F. J., C. V. Greenway, and D. S. Sitar. Hepatic blood flow: accuracy of estimation from infusions of indocyanine green in anesthetized cats. Br. J. Pharmacol. 91: 651–659, 1987.
 50. Burczynski, F. J., K. L. Pushka, D. S. Sitar, and C. V. Greenway. Hepatic plasma flow: accuracy of estimation from bolus injections of indocyanine green. Am. J. Physiol. 252 (Heart Circ. Physiol. 21): H953–H962, 1987.
 51. Burke, M. J., W. J. Stekiel, and J. H. Lombard. Reduced venoconstrictor reserve in spontaneously hypertensive rats subjected to hemorrhagic states. Circ. Shock 14: 25–37, 1984.
 52. Bynum, T. E., and J. W. Fara. Hepatic artery response to vasopressin. Am. J. Physiol. 239 (Gastrointest. Liver Physiol. 2): G378–G381, 1980.
 53. Caesar, J., S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin. Sci. 21: 43–57, 1961.
 54. Carneiro, J. J., and D. E. Donald. Blood reservoir function of dog spleen, liver, and intestine. Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H67–H72, 1977.
 55. Carneiro, J. J., and D. E. Donald. Change in liver blood flow and blood content in dogs during direct and reflex alteration of hepatic sympathetic nerve activity. Circ. Res. 40: 150–158, 1977.
 56. Carr, D. H., and D. A. Titchen. Postprandial changes in parotid salivary secretion and plasma osmolality and the effects of intravenous infusions of saline solutions. Q. J. Exp. Physiol. Cogn. Med. Sci. 63: 1–21, 1978.
 57. Charbon, G. A., and P. F. Hulstaert. Augmentation of arterial hepatic and renal flow by extracted and synthetic parathyroid hormone. Endocrinology 95: 621–626, 1974.
 58. Chou, C. C, and H. Siregar. Role of histamine H1‐and H2‐receptors in postprandial intestinal hyperemia. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G248–G252, 1982.
 59. Cohen, M. M., D. S. Sitar, J. R. McNeill,and C. V. Greenway. Vasopressin and angiotensin on resistance vessels of spleen, intestine, and liver. Am. J. Physiol. 218: 1704–1706, 1970.
 60. Cohn, J. N. Relationship of plasma volume changes to resistance and capacitance vessel effects of sympathomimetic amines and angiotensin in man. Clin. Sci. 30: 267–278, 1966.
 61. Cohn, J. N., I. M. Khatry, and R. J. Groszmann. Hepatic blood flow in alcoholic liver disease measured by an indicator dilution technique. Am. J. Med. 53: 704–714, 1972.
 62. Cohn, J. N., and A. L. Pinkerson. Intrahepatic distribution of hepatic arterial and portal venous flows in the dog. Am. J. Physiol. 216: 285–289, 1969.
 63. Cohn, R., and S. Kountz. Factors influencing control of arterial circulation in the liver of the dog. Am. J. Physiol 205: 1260–1264, 1963.
 64. Coleman, T. G., R. D. Manning, R. A. Norman, and A. C. Guyton. Control of cardiac output by regional blood flow distribution. Ann. Biomed. Eng. 2: 149–163, 1974.
 65. Combes, B., J. R. Preedy, H. O. Wheeler, R. M. Hays, and S. E. Bradley. The hemodynamic effects of hexamethonium bromide in the dog with special reference to “splanchnic pooling.” J. Clin. Invest. 36: 860–865, 1957.
 66. Comparini, L. Lymph. Vessels in the liver in man. Angiologica Basel 6: 262–274, 1969.
 67. Conrad, K. A., J. M. Byers, P. R. Finley and L. Burnham. Lidocaine elimination: effects of metoprolol and of propranolol. Clin. Pharmacol. Ther. 33: 133–138, 1983.
 68. Courtice, F. C., and A. W. Steinbeck. The effects of lymphatic obstruction and of posture on the absorption of protein from the peritoneal cavity. Aust. J. Exp. Biol. Med. Sci. 29: 451–458, 1951.
 69. Cousineau, D., C. A. Goresky, and C. P. Rose. Blood flow and norepinephrine effects on liver vascular and extravascular volumes. Am. J. Physiol. 244 (Heart Circ. Physiol. 13): H495–H504, 1983.
 70. Cousineau, D., C. A. Goresky, C. P. Rose, and S. Lee. Reflex sympathetic effects on liver vascular space and liver perfusion in dogs. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H186–H192, 1985.
 71. Daneshmend, T. K., M. D. Ene, G. Parker, and C. J. Roberts. Effects of chronic oral cimetidine on apparent liver blood flow and hepatic microsomal enzyme activity in man. Gut 25: 125–128, 1984.
 72. Davies, B. N., E. W. Horton, and P. G. Withrington. The occurrence of prostaglandin E2 in splenic venous blood of the dog following splenic nerve stimulation. Br. J. Pharmacol. 32: 127–135, 1968.
 73. Di Salvo, J., S. Britton, P. Galvas, and T. W. Sanders. Effects of angiotensin I and angiotensin II on canine hepatic vascular resistance. Circ. Res. 32: 85–92, 1973.
 74. Dive, C., A. C. Nadalini, and J. F. Heremans. Origin and composition of hepatic lymph proteins in the dog. Lymphology 4: 133–139, 1971.
 75. Donald, D. E. Mobilization of blood from the splanchnic circulation. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 193–201.
 76. Donald, D. E., and L. L. Aarhus. Active and passive release of blood from canine spleen and small intestine. Am. J. Physiol. 227: 1166–1172, 1974.
 77. Donn, K. H., J. R. Powell, J. F. Rogers, and J. R. Plachetka. Lack of effect of histamine H2‐receptor antagonists on indocyanine green disposition measured by two methods. J. Clin. Pharmacol. 24: 360–370, 1984.
 78. Drapanas, T., D. N. Kluge, and W. G. Schenk. Measurement of hepatic blood flow by bromsulphalein and by the electromagnetic flowmeter. Surgery St. Louis 48: 1017–1021, 1960.
 79. Eckstein, J. W., and W. K. Hamilton. The pressure‐volume responses of human forearm veins during epinephrine and norepinephrine infusions. J. Clin. Invest. 36: 1663–1671, 1957.
 80. Einzig, S., G. H. Rao, and J. G. White. Differential sensitivity of regional vascular beds in the dog to low‐dose prostacyclin infusion. Can. J. Physiol. Pharmacol. 58: 940–946, 1980.
 81. Elias, H., and J. C. Sherrick. Morphology of the Liver. New York: Academic, 1969.
 82. Epstein, S. E., G. D. Beiser, M. Stampfer, and E. Braunwald. Role of the venous system in baroreceptor‐mediated reflexes in man. J. Clin. Invest. 47: 139–152, 1968.
 83. Epstein, S. E., M. Stampfer, and G. D. Beiser. Role of the capacitance and resistance vessels in vasovagal syndrome. Circulation 37: 524–533, 1968.
 84. Evans, G. H., and Shand, D. G. Disposition of propranolol. VI. Independent variations in steady‐state circulating drug concentrations and half‐life as a result of plasma drug binding in man. Clin. Pharmacol. Ther. 14: 494–500, 1973.
 85. Ezzat, W. R., and W. W. Lautt. An adenosine mediated mechanism of hepatic arterial pressure‐flow autoregulation. Am. J. Physiol. 252 (Heart Circ. Physiol. 21): H836–H845, 1987.
 86. Fasth, S., L. Hulton, and S. Nordgren. Adjustments of hepatic and small intestine blood flow on selective vasoconstrictor fibre stimulation. Acta Physiol. Scand. 110: 343–350, 1980.
 87. Faxon, D. P., M. A. Creager, J. L. Halperin, H. Gavras, J. D. Coffman, and T. J. Ryan. Central and peripheral hemodynamic effects of angiotensin inhibition in patients with refractory congestive heart failure. Circulation 61: 925–930, 1980.
 88. Feely, J., D. Wade, C. B. McAllister, G. R. Wilkinson, and D. Robertson. Effect of hypotension on liver blood flow and lidocaine disposition. N. Engl. J. Med. 307: 866–869, 1982.
 89. Feely, J., G. R. Wilkinson, and A. J. Wood. Reduction of liver blood flow and propranolol metabolism by cimetidine. N. Engl. J. Med. 304: 692–695, 1981.
 90. Feely, J., and A. J. Wood. Effect on apparent liver blood flow of histamine‐receptor blockers and inhibition of prostaglandin synthesis. Clin. Pharmacol. Ther. 33: 91–94, 1983.
 91. Feely, J., and A. J. Wood. Effects of inhibitors of prostaglandin synthesis on hepatic drug clearance. Br. J. Clin. Pharmacol. 15: 109–111, 1983.
 92. Fernandez‐Muñoz, D., C. Caramelo, J. C. Santos, A. Blanchart, L. Hernando, and J. M. López‐Novoa. Systemic and splanchnic haemodynamic disturbances in conscious rats with experimental liver cirrhosis without ascites. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G316–G320, 1985.
 93. Folkow, B., D. H. Lewis, O. Lundgren, S. Mellander, and I. Wallentin. The effect of graded vasoconstrictor fibre stimulation on the intestinal resistance and capacitance vessels. Acta Physiol. Scand. 61: 445–457, 1964.
 94. Folkow, B., D. H. Lewis, O. Lundgren, S. Mellander, and I. Wallentin. The effect of the sympathetic vasoconstrictor fibres on the distribution of capillary blood flow in the intestine. Acta Physiol. Scand. 61: 458–466, 1964.
 95. Folkow, B., and S. Mellander. Veins and venous tone. Am. Heart J. 68: 397–408, 1964.
 96. Folkow, B., and E. Neil. Hemorrhage. In: Circulation, edited by B. Folkow and E. Neil. New York: Oxford Univ. Press, 1971, p. 548–555.
 97. Ford, R., R. Hainsworth, A. J. Rankin, and A. O. Soladoye. Abdominal vascular responses to changes in carbon dioxide tension in the cephalic circulation of anesthetized dogs. J. Physiol. Lond. 358: 417–431, 1985.
 98. Forker, E. L., and B. A. Luxon. Albumin binding and hepatic uptake: the importance of model selection. J. Pharm. Sci. 72: 1232–1233, 1983.
 99. Forker, E. L., and B. A. Luxon. Albumin‐mediated transport of rose bengal by perfused rat liver. J. Clin. Invest. 72: 1764–1771, 1983.
 100. Forker, E. L., and B. A. Luxon. Analyzing tracer disappearance curves to study hepatic transport kinetics. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G573–G577, 1983.
 101. Gallavan, R. H., C. C. Chou, P. R. Kvietys, and S. P. Sit. Regional blood flow during digestion in the conscious dog. Am. J. Physiol. 238 (Heart Circ. Physiol. 7): H220–H225, 1980.
 102. Gardner, M. L., and G. L. Atkins. Kinetic analysis of transport processes in the intestine and other tissues. Clin. Sci. 63: 405–414, 1982.
 103. Gelman, S., and E. A. Ernst. Role of pH, Pco2, and O2 content of portal blood in hepatic circulatory autoregulation. Am. J. Physiol. 233 (Endocrinol. Metab. Gastrointest. Physiol. 2): E255–E262, 1977.
 104. Gelman, S., and E. A. Ernst. Nitroprusside prevents adverse hemodynamic effects of vasopressin. Arch. Surg. 113: 1465–1471, 1978.
 105. Gilmore, N., J. R. Vane, and J. H. Wyllie. Prostaglandins released by the spleen. Nature Lond. 218: 1135–1140, 1968.
 106. Goresky, C. A. The lobular design of the liver: its effect on uptake process. In: Regulation of Hepatic Metabolism, edited by F. Lundquist and N. Tygstrup. New York: Academic, 1974, p. 808–819.
 107. Goresky, C. A. Cell membrane transport processes: their role in hepatic uptake. In: The Liver: Biology and Pathobiology, edited by I. Aries, H. Popper, D. Schacter, and D. A. Shafritz. New York: Raven, 1982, p. 581–599.
 108. Goresky, C. A. Kinetic interpretations of hepatic multiple‐indicator dilution studies. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G1–G12, 1983.
 109. Grainger, S. L., P. W. Keeling, I. M. Brown, J. H. Marigold, and R. P. Thompson. Clearance and non‐invasive determination of the hepatic extraction of indocyanine green in baboons and man. Clin. Sci. 64: 207–212, 1983.
 110. Granger, D. N., T. Miller, R. Allen, R. E. Parker, J. C. Parker, and A. E. Taylor. Permselectivity of cat liver blood‐lymph barrier to endogenous macromolecules. Gastroenterology 77: 103–109, 1979.
 111. Granger, D. N., P. D. Richardson, and A. E. Taylor. Volumetric assessment of the capillary filtration coefficient in the cat small intestine. Pfluegers Arch. 381: 25–33, 1979.
 112. Green, J. F. Mechanism of action of isoproterenol on venous return. Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H152–H156, 1977.
 113. Greenway, C. V. Effects of sodium nitroprusside, isosorbide. dinitrate, isoproterenol, phentolamine and prazosin on hepatic venous responses to sympathetic nerve stimulation in the cat. J. Pharmacol. Exp. Ther. 209: 56–61, 1979.
 114. Greenway, C. V. Discussion. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 224.
 115. Greenway, C. V. Hepatic fluid exchange. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 153–167.
 116. Greenway, C. V. Hepatic plethysmography. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 41–54.
 117. Greenway, C. V. Mechanisms and quantitative assessment of drug effects on cardiac output using a new model of the circulation. Pharmacol. Rev. 33: 213–251, 1981.
 118. Greenway, C. V. Autoregulatory escape in arteriolar resistance vessels. In: Smooth Muscle Contraction, edited by N. Stephens New York: Dekker, 1984, p. 473–484.
 119. Greenway, C. V. Role of splanchnic venous system in overall cardiovascular homeostasis. Federation Proc. 42: 1678–1684, 1983.
 120. Greenway, C. V. Liver. Physiology and pharmacology of blood circulation. In: Blood Vessels and Lymphatics in Organ Systems, edited by D. I. Abramson and P. B. Dobrin. Orlando, FL: Academic, 1984, p. 477–489.
 121. Greenway, C. V. Neural control and autoregulatory escape. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd and D. N. Granger. New York: Raven, 1984, p. 61–71.
 122. Greenway, C. V., and F. J. Burczynski. Effects of liver blood flow on hepatic uptake kinetics of galactose in anesthetized cats: parallel tube model. Can. J. Physiol. Pharmacol. 65: 1193–1199, 1987.
 123. Greenway, C. V., and I. R. Innes. Effects of splanchnic nerve stimulation on cardiac preload, afterload and output in cats. Circ. Res. 46: 181–189, 1980.
 124. Greenway, C. V., and I. R. Innes. Effects of arteriolar vasodilators on hepatic venous compliance and cardiac output in anesthetized cats. J. Cardiovasc. Pharmacol. 3: 1321–1331, 1981.
 125. Greenway, C. V., and I. R. Innes. Effects of carotid sinus baroreceptor reflex on responses to phenylephrine and nitro‐prusside in anesthetized cats. J. Cardiovasc. Pharmacol. 3: 169–177, 1981.
 126. Greenway, C. V., and W. W. Lautt. Effects of hepatic venous pressure on transsinusoidal fluid transfer in the liver of the anesthetized cat. Circ. Res. 26: 697–703, 1970.
 127. Greenway, C. V., and W. W. Lautt. Effects of adrenaline, isoprenaline and histamine on transsinusoidal fluid filtration in the cat liver. Br. J. Pharmacol. 44: 185–191, 1972.
 128. Greenway, C. V., and W. W. Lautt. Effects of infusions of catecholamines, angiotensin, vasopressin and histamine on hepatic blood volume in the anaesthetized cat. Br. J. Pharmacol. 44: 177–184, 1972.
 129. Greenway, C. V., and A. E. Lawson. Beta‐adrenergic receptors in the hepatic arterial bed of the anesthetized cat. Can. J. Physiol. Pharmacol. 47: 415–419, 1969.
 130. Greenway, C. V., A. E. Lawson, and S. Mellander. The effects of stimulation of the hepatic nerves, infusions of noradrenaline and occlusion of the carotid arteries on liver blood flow in the anaesthetized cat. J. Physiol. Lond. 192: 21–41, 1967.
 131. Greenway, C. V., A. E. Lawson, and R. D. Stark. The effect of haemorrhage on hepatic artery and portal vein flows in the anesthetized cat. J. Physiol. Lond. 193: 375–379, 1967.
 132. Greenway, C. V., and G. E. Lister. Capacitance effects and blood reservoir function in the splanchnic vascular bed during non‐hypotensive haemorrhage and blood volume expansion in anaesthetized cats. J. Physiol. Lond. 237: 279–294, 1974.
 133. Greenway, C. V., and G. Oshiro. Comparison of the effects of hepatic nerve stimulation on arterial flow, distribution of arterial and portal flows and blood content in the livers of anaesthetized cats and dogs. J. Physiol. Lond. 227: 487–501, 1972.
 134. Greenway, C. V. and G. Oshiro. Intrahepatic distribution of portal and hepatic arterial blood flows in anaesthetized cats and dogs and the effects of portal occlusion, raised venous pressure and histamine. J. Physiol. Lond. 227: 473–485, 1972.
 135. Greenway, C. V., and G. Oshiro. Effects of histamine on hepatic volume (outflow block) in anaesthetized dogs. Br. J. Pharmacol. 47: 282–290, 1973.
 136. Greenway, C. V., G. D. Scott, and J. Zink. Sites of autoregulatory escape of blood flow in the mesenteric vascular bed. J. Physiol. Lond. 259: 1–12, 1976.
 137. Greenway, C. V., K. L. Seaman, and I. R. Innes. Norepinephrine on venous compliance and unstressed volume in cat liver. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H468–H476, 1985.
 138. Greenway, C. V., and R. D. Stark. Vascular responses of the spleen to rapid haemorrhage in the anaesthetized cat. J. Physiol. Lond. 204: 169–179, 1969.
 139. Greenway, C. V., and R. D. Stark. Hepatic vascular bed. Physiol. Rev. 51: 23–65, 1971.
 140. Greenway, C. V., R. D. Stark, and W. W. Lautt. Capacitance responses and fluid exchange in the cat liver during stimulation of the hepatic nerves. Circ. Res. 25: 277–284, 1969.
 141. Griffith, F. R.Jr., and F. E. Emery. The vasomotor control of the liver circulation. Am. J. Physiol. 95: 20–34, 1930.
 142. Grillner, S., J. Nilsson, and A. Thorstensson. Intra‐abdominal pressure changes during natural movements in man. Acta Physiol. Scand. 103: 275–283, 1978.
 143. Grisham, J. W., W. Nopanitaya, J. Compagno, and A. E. Nagel. Scanning electron microscopy of normal rat liver: the surface structure of its cells and tissue components. Am. J. Anat. 144: 295–322, 1975.
 144. Groom, A. C., S. Rowlands, and H. W. Thomas. Some circulatory responses to haemorrhage in the cat. Q. J. Exp. Physiol. 50: 385–405, 1965.
 145. Groszmann, R. J. The measurement of liver blood flow using clearance techniques. Hepatology Baltimore 3: 1039–1040, 1983.
 146. Groszmann, R. J., A. T. Blei, J. L. Kniaz, E. H. Storer, and H. O. Conn. Portal pressure reduction induced by partial mechanical obstruction of the superior mesenteric artery in the anaesthetized dog. Gastroenterology 75: 187–192, 1978.
 147. Groszmann, R. J., J. Vorobioff, and E. Riley. Splanchnic hemodynamics in portal‐hypertensive rats: measurements with γ‐labelled microsphere. Am. J. Physiol. 242 (Gastrointest. Liver Physiol. 5): G156–G160, 1982.
 148. Gumucio, D. L. Functional and anatomic heterogeneity in the liver acinus: impact on transport. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G578–G582, 1983.
 149. Gumucio, D. L., J. J. Gumucio, J. A. Wilson, C. Cutter, M. Krauss, R. Caldwell, and E. Chen. Albumin influences sulfobromophthalein transport by hepatocytes of each acinar zone. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G86–G95, 1984.
 150. Gumucio, J. J., and D. L. Miller. Functional implications of liver cell heterogeneity. Gastroenterology 80: 393–403, 1981.
 151. Gurll, N. J., D. G. Reynolds, D. Coon, and S. S. Shirazi. Acute and chronic splanchnic blood flow responses to portacaval shunt in the normal dog. Gastroenterology 78: 1432–1436, 1980.
 152. Guth, P. H., and E. Smith. Histamine receptors in mesenteric circulation of the cat and rat. Am. J. Physiol. 234 (Endocrinol. Metab. Gastrointest. Physiol. 3): E370–E374, 1978.
 153. Hainsworth, R., and F. Karim. Responses of abdominal vascular capacitance in the anaesthetized dog to changes in carotid sinus pressure. J. Physiol. Lond. 262: 659–677, 1976.
 154. Hainsworth, R., F. Karim, K. H. McGregor, and A. J. Rankin. Effects of stimulation of aortic chemoreceptors on abdominal vascular resistance and capacitance in anaesthetized. dogs. J. Physiol. Lond. 334: 421–431, 1983.
 155. Hainsworth, R., F. Karim, K. H. McGregor, and L. M. Wood. Hind limb vascular capacitance responses in anaesthetized dogs. J. Physiol. Lond. 337: 417–428, 1983.
 156. Hainsworth, R., F. Karim, K. H. McGregor, and L. M. Wood. Responses of abdominal vascular resistance and capacitance to stimulation of carotid chemoreceptors in anaesthetized dogs. J. Physiol. Lond. 334: 409–419, 1983.
 157. Hainsworth, R., F. Karim, and J. B. Stoker. The influence of aortic baroreceptors on venous tone in the perfused hind limb of the dog. J. Physiol. Lond. 244: 337–351, 1975.
 158. Hanson, K. M. Vascular response of intestine and liver to intravenous infusion of vasopressin. Am. J. Physiol. 219: 779–784, 1970.
 159. Hanson, K. M. Escape of the liver vasculature from adrenergic vasoconstriction. Proc. Soc. Exp. Biol. Med. 141: 385–390, 1972.
 160. Hanson, K. M. Dilator responses of the canine hepatic vasculature. Angiologica Basel 10: 15–23, 1973.
 161. Hanson, K. M., and P. C. Johnson. Local control of hepatic arterial and portal venous flow in the dog. Am. J. Physiol. 211: 712–720, 1966.
 162. Hase, T., and J. Brim. Observations on microcirculatory architecture of rat liver. Anat. Rec. 156: 157–174, 1966.
 163. Heinzow, B., H. Corbett, S. Constantinides, R. Bourne, and A. J. McLean. Interaction between oral hydralazine and propranolol. I. Changes in absorption, presystemic clearance and splanchnic blood flow. J. Pharmacol. Exp. Ther. 229: 509–514, 1984.
 164. Henderson, J. M., and S. S. Hanna. Effective liver blood flow: determination by galactose clearance. Can. J. Surg. 26: 129–132, 1983.
 165. Hinshaw, L. B., D. A. Reins, and R. J. Hill. Responses of isolated liver to endotoxin. Can. J. Physiol. Pharmacol. 44: 529–541, 1966.
 166. Hollenberg, M., and J. Dougherty. Liver blood flow measured by portal venous and hepatic arterial routes with Kr85. Am. J. Physiol. 210: 926–932, 1966.
 167. Horvath, S. M., T. Kelly, G. E. Folk, Jr., and B. K. Hutt. Measurement of blood volumes in the splanchnic bed of the dog. Am. J. Physiol. 189: 573–575, 1957.
 168. Huet, P., and J. Villeneuve. Determinants of drug disposition in patients with cirrhosis. Hepatology Baltimore 3: 913–918, 1983.
 169. Hughes, R. L., R. T. Mathie, D. Campbell, and W. Fitch. Effect of hypercarbia on hepatic blood flow and oxygen consumption in the greyhound. Br. J. Anaesth. 51: 289–296, 1979.
 170. Hughes, R. L., R. T. Mathie, D. Campbell, and W. Fitch. Systemic hypoxia and hyperoxia, and liver blood flow and oxygen consumption in the greyhound. Pfluegers Arch. 381: 151–157, 1979.
 171. Hughes, R. L., R. T. Mathie, W. Fitch, and D. Campbell. Liver blood flow and oxygen consumption during metabolic acidosis and alkalosis in the greyhound. Clin. Sci. 60: 355–361, 1980.
 172. Hutter, J. F., H. M. Piper, and P. G. Spieckermann. Kinetic analysis of myocardial fatty acid oxidation suggesting an albumin receptor mediated uptake process. J. Mol. Cell. Cardiol. 16: 219–226, 1984.
 173. Hyatt, R. E., G. H. Lawrence, and J. R. Smith. Observations on the origin of ascites from experimental hepatic congestion. J. Lab. Clin. Med. 45: 274–280, 1955.
 174. Iga, T., and C. D. Klaassen. Hepatic extraction of nonmetabolizable xenobiotics in rats. J. Pharmacol. Exp. Ther. 211: 690–697, 1979.
 175. Ilebekk, A., J. Thorvaldson, and F. Kiil. Left ventricular function during acute elevation of aortic blood pressure in dogs. Am. J. Physiol. 231: 1476–1484, 1976.
 176. Israel, Y., H. Kalant, H. Orrego, J. M. Khanna, L. Videla, and J. M. Phillips. Experimental alcohol‐induced hepatic necrosis: suppression by propylthiouracil. Proc. Natl. Acad. Sci. USA 72: 1137–1141, 1975.
 177. Israel, Y., and H. Orrego. Hepatocyte demand and substrate supply as factors in the susceptibility to alcoholic injury: pathogenesis and prevention. Clin. Gastroenterol. 10: 355–373, 1981.
 178. JÄrhult, J. Comparative effects of angiotensin and noradrenaline on resistance, capicitance, and precapillary sphincter vessels in cat skeletal muscle. Acta Physiol. Scand. 81: 315–324, 1971.
 179. Johns, B. L., and C. F. Rothe. Delayed vascular compliance and fluid exchange in the canine intestine. Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H660–H669, 1978.
 180. Johnson, P. C. Effect of venous pressure on mean capillary pressure and vascular resistance in the intestine. Circ. Res. 16: 294–300, 1965.
 181. Johnson, P. C., and K. M. Hanson. Relation between venous pressure and blood volume in the intestine. Am. J. Physiol. 204: 31–34, 1963.
 182. Johnson, P. C., and K. M. Hanson. Capillary filtration in the small intestine of the dog. Circ. Res. 19: 766–773, 1966.
 183. Jones, D. B., D. J. Morgan, G. W. Mihaly, L. K. Webster, and R. A. Smallwood. Discrimination between the venous equilibrium and sinusoidal models of hepatic drug elimination in the isolated perfused rat liver by perturbation of propranolol protein binding. J. Pharmacol. Exp. Ther. 229: 522–526, 1984.
 184. Kahn, D., R. van Hoorn‐Hickman, and J. Terblanche. Liver blood flow after partial hepatectomy in the pig. J. Surg. Res. 37: 290–294, 1984.
 185. Kaiser, G. A., J. Ross, and E. Braunwald. α‐ and β‐adrenergic receptor mechanisms in the systemic venous bed. J. Pharmacol. Exp. Ther. 144: 156–162, 1964.
 186. Karim, F., and R. Hainsworth. Responses of abdominal vascular capacitance to stimulation of splanchnic nerves. Am. J. Physiol. 231: 434–440, 1976.
 187. Karim, F., R. Hainsworth, and R. P. Pandey. Reflex responses of abdominal vascular capacitance from aortic baroreceptors in dog. Am. J. Physiol. 235: (Heart Circ. Physiol. 4): H488–H493, 1978.
 188. Kaufman, M. P., K. J. Rybicki, T. G. Waldrop, and J. H. Mitchell. Effect on arterial pressure of rhythmically contracting the hindlimb muscles of cats. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 56: 1265–1271, 1984.
 189. Keiding, S. Hepatic elimination kinetics: the influence of hepatic blood flow on clearance determinations. Scand. J. Clin. Lab. Invest. 36: 113–118, 1976.
 190. Keiding, S., and P. B. Andreasen. Hepatic clearance measurements and pharmacokinetics. Pharmacology Basel 19: 105–110, 1979.
 191. Keiding, S., and L. Bass. Galactose clearance as a measure of hepatic blood flow. Gastroenterology 85: 986–987, 1983.
 192. Keiding, S., and E. Chiarantini. Effect of sinusoidal perfusion on galactose elimination kinetics in perfused rat liver. J. Pharmacol. Exp. Ther. 205: 465–470, 1978.
 193. Keiding, S., and K. Priisholm. Current models of hepatic pharmacokinetics: flow effects on kinetic constants of ethanol elimination in perfused rat liver. Biochem. Pharmacol. 20: 3209–3212, 1984.
 194. Keiding, S., and E. Steiness. Flow dependence of propranolol elimination in perfused rat liver. J. Pharmacol. Exp. Ther. 230: 474–477, 1984.
 195. Keller, F., and J. Scholle. Criticism of pharmacokinetic clearance concepts. Int. J. Clin. Pharmacol. Ther. Toxicol. 21: 563–568, 1983.
 196. Kerr, J. C., R. W. Hobson, R. F. Seelig, and K. G. Swan. Vasopressin: route of administration and effects on canine hepatic and superior mesenteric arterial blood flows. Ann. Surg. 187: 137–142, 1978.
 197. Klaassen, C. D., and G. L. Plaa. Plasma disappearance and biliary excretion of indocyanine green in rats, rabbits and dogs. Toxicol. Appl. Pharmacol. 15: 374–384, 1969.
 198. Knisely, M. H., F. Harding, and H. Debacker. Hepatic. sphincters. Science Wash. DC 125: 1023–1026, 1957.
 199. Knodell, R. G., R. M. Farleigh, N. M. Steele, and J. H. Bond. Effects of liver congestion on hepatic drug metabolism in the rat. J. Pharmacol. Exp. Ther. 221: 52–57, 1982.
 200. Koo, A., and I. Y. Liang. Blood flow in hepatic sinusoids in experimental hemorrhagic shock in the rat. Microvasc. Res. 13: 315–325, 1977.
 201. Koo, A., and I. Y. Liang. Microvascular filling pattern in rat liver sinusoids during vagal stimulation. J. Physiol. Lond. 295: 191–199, 1979.
 202. Koo, A., and I. Y. Liang. Vagus‐mediated vasodilator tone in the rat terminal liver microcirculation. Microvasc. Res. 18: 413–420, 1979.
 203. Koo, A., I. Y. Liang, and K. K. Cheng. The terminal hepatic microcirculation in the rat. Q. J. Exp. Physiol. 60: 261–266, 1975.
 204. Kraan, W. J., G. H. Huisman, and J. Velthuizen. Splenic storage volume in the unanesthetized resting beagle. Eur. J. Appl. Physiol. 38: 197–206, 1978.
 205. Krarup, N. The effect of hemorrhage on hepatosplanchnic hemodynamics, liver function and hepatic metabolism. Acta Physiol. Scand. 89: 269–277, 1973.
 206. Krarup, N. The effects of noradrenaline and adrenaline on hepatosplanchnic hemodynamics, functional capacity of the liver and hepatic metabolism. Acta Physiol. Scand. 87: 307–319, 1973.
 207. Krarup, N. Effects of histamine, vasopressin and angiotensin II on hepatosplanchnic hemodynamics, liver function and hepatic metabolism in cats. Acta Physiol. Scand. 95: 311–317, 1975.
 208. Kullmann, R., W. R. Breull, K. Wassermann, and A. Konopatzki. Blood flow redistribution by dopamine in the feline gastrointestinal tract. Naunyn‐Schmiedeberg's Arch. Pharmacol. 323: 145–148, 1983.
 209. Lacroix, E., and I. Leusen. Splanchnic and general hemodynamics after acute hemorrhage in the anaesthetized dog. Arch. Int. Physiol. Biochim. 75: 12–26, 1967.
 210. Laine, G. A., J. T. Hall, S. H. Laine, and H. J. Granger. Transsinusoidal fluid dynamics in canine liver during venous hypertension. Circ. Res. 45: 317–323, 1979.
 211. Larsen, J. A., N. Krarup, and A. Munck. Liver hemodynamics and liver function in cats during graded hypoxic hypoxemia. Acta Physiol. Scand. 98: 257–262, 1976.
 212. Lautt, W. W. Control of hepatic and intestinal blood flow: effect of isovolemic haemodilution on blood flow and oxygen uptake in the intact liver and intestines. J. Physiol. Lond. 265: 313–326, 1977.
 213. Lautt, W. W. Effects of acute, passive hepatic congestion on blood flow and oxygen uptake in the intact liver of the cat. Circ. Res. 41: 787–790, 1977.
 214. Lautt, W. W. Effect of stimulation of hepatic nerves on hepatic O2 uptake and blood flow. Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H652–H656, 1977.
 215. Lautt, W. W. The hepatic artery: subservient to hepatic metabolism or guardian of normal hepatic clearance rates of humoral substances. Gen. Pharmacol. 8: 73–78, 1977.
 216. Lautt, W. W. Hepatic vasculature: a conceptual review. Gastroenterology 73: 1163–1169, 1977.
 217. Lautt, W. W. Neural activation of α‐adrenoreceptors in glucose mobilization from the liver. Can. J. Physiol. Pharmacol. 57: 1037–1039, 1979.
 218. Lautt, W. W. Control of hepatic arterial blood flow: independence from liver metabolic activity. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H559–H564, 1980.
 219. Lautt, W. W. Hepatic nerves: a review of their functions and effects. Can. J. Physiol. Pharmacol. 58: 105–123, 1980.
 220. Lautt, W. W. Evaluation of surgical denervation of the liver in cats. Can. J. Physiol. Pharmacol. 59: 1013–1016, 1981.
 221. Lautt, W. W. Hepatic Circulation in Health and Disease. New York: Raven, 1981.
 222. Lautt, W. W. Role and control of the hepatic artery. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 203–226.
 223. Lautt, W. W. Carotid sinus baroreceptor effects on cat livers in control and hemorrhaged states. Can. J. Physiol. Pharmacol. 60: 1592–1602, 1982.
 224. Lautt, W. W. Afferent and efferent neural roles in liver function. Prog. Neurobiol. Oxford 21: 323–348, 1983.
 225. Lautt, W. W. Relationship between hepatic blood flow and overall metabolism: the hepatic arterial buffer response. Federation Proc. 42: 1662–1666, 1983.
 226. Lautt, W. W. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: the hepatic arterial buffer response. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G549–G556, 1985.
 227. Lautt, W. W., L. C. Brown, and J. S. Durham. Active and passive control of hepatic blood volume responses to hemorrhage at normal and raised hepatic venous pressures in cats. Can. J. Physiol. Pharmacol. 58: 1049–1057, 1980.
 228. Lautt, W. W., and A. M. Carroll. Evaluation of topical phenol as a means of producing autonomic denervation of the liver. Can. J. Physiol. Pharmacol. 62: 849–853, 1984.
 229. Lautt, W. W., and M. G. CÔTÉ. Functional evaluation of 6‐hydroxy‐dopamine‐induced sympathectomy in the liver of the cat. J. Pharmacol. Exp. Ther. 198: 562–567, 1976.
 230. Lautt, W. W., and T. R. Daniels. Differential effect of taurocholic acid on hepatic arterial resistance vessels and bile flow. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G366–G369, 1983.
 231. Lautt, W. W., P. D. Dwan, and R. R. Singh. Control of the hyperglycemic response to hemorrhage in cats. Can. J. Physiol. Pharmacol. 60: 1618–1623, 1982.
 232. Lautt, W. W., and C. V. Greenway. Hepatic capacitance vessel responses to bilateral carotid occlusion in anesthetized cats. Can. J. Physiol. Pharmacol. 50: 244–247, 1972.
 233. Lautt, W. W., and C. V. Greenway. Hepatic venous compliance and role of liver as a blood reservoir. Am. J. Physiol. 231: 292–295, 1976.
 234. Lautt, W. W., C. V. Greenway, and D. J. Legare. Effect of hepatic nerves, norepinephrine, angiotensin, elevated central venous pressure on postsinusoidal resistance sites and intrahepatic pressures. Microvasc. Res. 33: 50–61, 1987.
 235. Lautt, W. W., C. V. Greenway, D. J. Legare, and H. Wweisman. Localization of intrahepatic portal vascular resistance. Am. J. Physiol. 251 (Gastrointest. Liver Physiol. 14): G375–G381, 1986.
 236. Lautt, W. W., and D. J. Legare. Adenosine modulation of hepatic arterial but not portal venous constriction induced by sympathetic nerves, norepinephrine, angiotensin and vasopressin. Can. J. Physiol. Pharmacol. 64: 449–454, 1986.
 237. Lautt, W. W., and D. J. Legare. The use of 8‐phenyltheophylline as a competitive antagonist of adenosine and inhibitor of the intrinsic regulatory mechanism of the hepatic artery. Can. J. Physiol. Pharmacol. 63: 717–722, 1985.
 238. Lautt, W. W., and D. J. Legare. Effect of histamine, norepinephrine and nerves on vascular resistance and pressures in dog liver. Am. J. Physiol. 252 (Gastrointest. Liver Physiol. 15): G472–G478, 1987.
 239. Lautt, W. W., D. J. Legare, and M. S. D'Almeida. Adenosine as putative regulator of hepatic arterial flow (the buffer response). Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H331–H338, 1985.
 240. Lautt, W. W., D. J. Legare, and T. R. Daniels. The comparative effect of administration of substances via the hepatic artery or portal vein on hepatic arterial resistance, liver blood volume, and hepatic extraction in cats. Hepatology Baltimore 4: 927–932, 1984.
 241. Lautt, W. W., T. L. MacLachlan, and L. C. Brown. The effect of hypertonic infusions on hepatic blood flows and liver volume in the cat. Can. J. Physiol. Pharmacol. 55: 1339–1344, 1977.
 242. Lautt, W. W., and F. S. Skelton. Effect of hepatic nerve. stimulation on hepatic uptake of lidocaine in the cat. Life Sci. 19: 433–436, 1976.
 243. Lautt, W. W., and F. S. Skelton. The effect of SKF‐525A and of altered hepatic blood flow on lidocaine clearance in the cat. Can. J. Physiol. Pharmacol. 55: 7–12, 1976.
 244. Lautt, W. W., and C. Wong. Hepatic parasympathetic neural effect on glucose balance in the intact liver. Can. J. Physiol. Pharmacol. 56: 679–682, 1978.
 245. Lebrec, D., and L. Blanchet. Effect of two models of portal hypertension on splanchnic organ blood flow in the rat. Clin. Sci. 68: 23–28, 1985.
 246. Leevy, C. M., C. L. Mendenhall, W. Lesko, and M. M. Howard. Estimation of hepatic blood flow with indocyanine green. J. Clin. Invest. 41: 1169–1179, 1962.
 247. Legare, D. J., and W. W. Lautt. Hepatic venous resistance site in the dog: localization and validation of intrahepatic pressure measurements. Can. J. Physiol. Pharmacol. 65: 352–359, 1987.
 248. Leiberman, D. P., R. T. Mathie, A. M. Harper, and L. H. Blumgart. The hepatic arterial and portal venous circulations of the liver studied with krypton‐85 clearance technique. J. Surg. Res. 25: 154–162, 1978.
 249. Lesh, T. A., and C. F. Rothe. Sympathetic and hemodynamic effects on capacitance vessels in dog skeletal muscle. Am. J. Physiol. 217: 819–827, 1969.
 250. Lutz, J., H. Henrich, and E. Bauereisen. Oxygen supply and uptake in the liver and intestine. Pfluegers Arch. 360: 7–15, 1975.
 251. Lutz, J., and H. Schultze. Oxygen consumption and oxygen extraction of the feline liver under different types of induced hypoxia. In: Oxygen Transport to Tissue, edited by I. A. Silver, M. Erecinska, and H. I. Bicher. New York: Plenum, 1978, vol. 3, p. 537–543.
 252. Luxon, B. A., and E. L. Forker. Simulation and analysis of hepatic indicator dilution curves. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G76–G89, 1982.
 253. Marshall, J. M. The influence of the sympathetic nervous system on individual vessels of the microcirculation of skeletal muscle of the cat. J. Physiol. Lond. 332: 169–186, 1982.
 254. Mason, D. T., and E. Braunwald. Effects of guanethidine, reserpine and methyldopa on reflex venous and arterial constriction in man. J. Clin. Invest. 43: 1449–1463, 1964.
 255. Mathie, R. T., and L. H. Blumgart. Effect of denervation on the hepatic haemodynamic response to hypercapnia and hypoxia in the dog. Pfluegers Arch. 397: 152–157, 1983.
 256. Mathie, R. T., and L. H. Blumgart. The hepatic haemodynamic response to acute portal venous blood flow reductions in the dog. Pfluegers Arch. 399: 223–227, 1983.
 257. Mathie, R. T., D. P. Leiberman, A. M. Harper, and L. H. Blumgart. The role of blood flow in the control of liver size. J. Surg. Res. 27: 139–144, 1979.
 258. Matsuno, H. Study on the hepatic circulation. Jpn. Circ. J. 33: 387–397, 1969.
 259. McDevitt, D. G., A. S. Nies, and G. R. Wilkinson. Influence of phenobarbital on factors responsible for hepatic clearance of indocyanine green in the rat: relative contributions of induction and altered liver blood flow. Biochem. Pharmacol. 26: 1247–1250, 1977.
 260. McGrath, M. A., and J. T. Shepherd. Hyperosmolarity: effects on nerves and smooth muscle of cutaneous veins. Am. J. Physiol. 231: 141–147, 1976.
 261. McKay, T., J. Zink, and C. V. Greenway. Relative rates of absorption of fluid and protein from the peritoneal cavity in cats. Lymphology 11: 106–110, 1978.
 262. McLain, G. E., I. G. Sipes, and B. B. Brown. An animal model of halothane hepatotoxicity. Anesthesiology 51: 321–326, 1979.
 263. McLean, A. J., P. J. McNamara, P. DuSouich, M. Gibaldi, and D. Lalka. Food, splanchnic blood flow, and bioavailability of drugs subject to first‐pass metabolism. Clin. Pharmacol. Ther. 24: 5–10, 1978.
 264. Mellander, S. Comparative studies on the adrenergic neuro‐hormonal control of resistance and capacitance vessels in the cat. Acta Physiol. Scand. Suppl. 176: 1–86, 1960.
 265. Mellander, S., and B. Johansson. Control of resistance, exchange and capacitance functions in the peripheral circulation. Pharmacol. Rev. 20: 117–196, 1968.
 266. Mendoza, A. E., C. C. Genstler, R. D. Gilbert, and G. G. Power. Vascular compliance in the adult cat liver (Abstract). Clin. Res. 29: 15, 1981.
 267. Merritt, F. L., and A. M. Weissler. Reflex venomotor alterations during exercise and hyperventilation. Am. Heart J. 58: 382–387, 1959.
 268. Messerli, F. H., W. Nowaczynski, M. Honda, J. Genest, R. Boucher, O. Kuchel, and J. M. Rojo‐Ortega. Effects of angiotensin II on steroid metabolism and hepatic blood flow in man. Circ. Res. 40: 204–207, 1977.
 269. Miller, D. L. Quantitative morphological assessment of the sinusoids of the hepatic acinus. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 111–135.
 270. Mitzner, W. Hepatic outflow resistance, sinusoidal pressure, and the vascular waterfall. Am. J. Physiol. 227: 513–519, 1974.
 271. Morgan, D. J., and K. Raymond. Use of the unbound drug concentration in blood to discriminate between two models of hepatic drug elimination. J. Pharm. Sci. 71: 600–602, 1982.
 272. Moritoki, H. Possible mechanism of potentiation of the action of adenosine by some vasodilators. In: Physiology and Pharmacology of Adenosine Derivatives, edited by J. W. Daly, Y. Kuroda, J. W. Phillis, H. Shimizu, and M. Ui. New York: Raven, 1983, p. 197–207.
 273. Mostbeck, A., H. Partsch, and L. Peschl. Investigations on peripheral blood distribution. In: Third Adalat Symposium, edited by A. D. Jatene and P. R. Lichtlen. Amsterdam: Excerpta Mèdica, 1976, p. 91–97.
 274. Motooka, T. Influence of bleeding and acetylcholine on the hepatic circulation. Jpn. Circ. J. 33: 95–104, 1969.
 275. Motta, P., M. Muto, and T. Fujita. The Liver: An Atlas of Scanning Electron Microscopy. Tokyo: Igaku Shoin, 1978.
 276. Mundschau, G. A., S. W. Zimmerman, J. W. Gildersleeve, and Q. R. Murphy. Hepatic and mesenteric artery resistances after sinoaortic denervation and hemorrhage. Am. J. Physiol. 211: 77–82, 1966.
 277. Nakata, K., G. F. Leong, and R. W. Brauer. Direct measurement of blood pressures in minute vessels of the liver. Am. J. Physiol. 199: 1181–1188, 1960.
 278. Nies, A. S., D. G. Shand, and G. R. Wilkinson. Altered hepatic blood flow and drug disposition. In: Handbook of Clinical Pharmacokinetics, edited by L. F. Prescott and M. Gibaldi. Auckland, New Zealand: Adis, 1983, p. 75–96.
 279. Nies, A. S., G. R. Wilkinson, B. D. Rush, J. T. Strother, and D. G. McDevitt. Effects of alteration of hepatic microsomal enzyme activity on liver blood flow in the rat. Biochem. Pharmacol. 25: 1991–1993, 1976.
 280. Nilsson, H., and B. Folkow. Structurally reduced compliance of the venous capacitance vessels in spontaneously hypertensive rats (SHR). Acta Physiol. Scand. 110: 215–217, 1980.
 281. Nopanitaya, W., J. C. Lamb, J. W. Grisham, and J. L. Carson. Effect of hepatic venous outflow obstruction on pores and fenestration in sinusoidal endothelium. Br. J. Exp. Path. 57: 604–609, 1976.
 282. Nxumalo, J. L., M. Teranaka, and W. G. Schenk. Hepatic blood flow measurement. Arch. Surg. 113: 169–172, 1978.
 283. Oberg, B. The relationship between active constriction and passive recoil of the veins at various distending pressures. Acta Physiol. Scand. 71: 233–247, 1967.
 284. Oberg, B., and S. Rosell. Sympathetic control of consecutive vascular sections in canine subcutaneous adipose tissue. Acta Physiol. Scand. 71: 47–56, 1967.
 285. Oberg, B., and S. White. Circulatory effects of interruption and stimulation of cardiac vagal afferents. Acta Physiol. Scand. 80: 383–394, 1970.
 286. Ockner, R. K., R. A. Weisiger, and J. L. Gollan. Hepatic uptake of albumin‐bound substances: albumin receptor concept. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G13–G18, 1983.
 287. Ohnhaus, E. E. The distribution of Rb86 in different parts of the liver. Pfluegers Arch. 346: 157–161, 1974.
 288. Orrego, H., H. Kalant, Y. Israel, J. Blake, A. Medline, J. G. Rankin, A. Armstrong, and B. Kapur. Effect of short‐term therapy with propylthiouracil in patients with alcoholic liver disease. Gastroenterology 76: 105–115, 1975.
 289. Pamnani, M. B., G. Simon, and H. W. Overbeck. Increased mesenteric blood flow and decreased mesenteric venous compliance in dogs with chronic perinephritic hypertension. Proc. Soc. Exp. Biol. Med. 161: 397–401, 1979.
 290. Pang, K. S., and M. Rowland. Hepatic clearance of drugs. I. Theoretical considerations of a “well‐stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding and the hepatocellular enzymatic activity on hepatic drug clearance. J. Pharmacokinet. Biopharm. 5: 625–653, 1977.
 291. Pang, K. S., and M. Rowland. Hepatic clearance of drugs. II. Experimental evidence for acceptance of the “well‐stirred” model over the “parallel tube” model using lidocaine in the perfused rat liver in situ preparation. J. Pharmacokinet. Biopharm. 5: 655–680, 1977.
 292. Parker, G., T. K. Daneshmend, and C. J. Roberts. Do β‐blockers differ in their effects on hepatic microsomal enzymes and liver blood flow? J. Clin. Pharmacol. 24: 493–499, 1984.
 293. Patel, P., D. Bose, and C. V. Greenway. Effects of prazosin and phenoxybenzamine on α‐ and β‐receptor‐mediated responses in intestinal resistance and capacitance vessels. J. Cardiovasc. Pharmacol. 3: 1050–1059, 1981.
 294. Pirttiaho, H. I., E. A. Sotaniemi, R. O. Pelkonen, and U. Pitkanen. Hepatic blood flow and drug metabolism in patients on enzyme‐inducing anticonvulsants. Eur. J. Clin. Pharmacol. 22: 441–445, 1982.
 295. Plaa, G. L. Toxicology of the liver. In: Toxicology: The Basic Science of Poisons, edited by L. J. Casarett and J. Doull. New York: Macmillan, 1975, p. 170–189.
 296. Post, J. A., and K. M. Hanson. Hepatic vascular and biliary responses to infusion of gastrointestinal hormones and bile salts. Digestion 12: 65–77, 1975.
 297. Price, H. L., S. Deutsch, B. E. Marshall, G. W. Stephen, M. G. Behar, and G. R. Neufeld. Hemodynamic and metabolic effects of hemorrhage in man, with particular reference to the splanchnic circulation. Circ. Res. 18: 469–474, 1966.
 298. Price, J. B., P. W. McFate, and R. F. Shaw. Dynamics of blood flow through the canine liver. Surgery 56: 1109–1120, 1964.
 299. Rappaport, A. M. The microcirculatory hepatic unit. Microvasc. Res. 6: 212–228, 1973.
 300. Rappaport, A. M. The microcirculatory hepatic unit. In: Drugs and the Liver, edited by F. K. Schuttauer New York: Springer‐Verlag, 1975, p. 425–434.
 301. Rappaport, A. M. The acinus‐microvascular unit of the liver. In: Hepatic Circulation in Health and Disease, edited by W. W. Lautt New York: Raven, 1981, p. 175–192.
 302. Reilly, F. D., R. V. Dimlich, E. V. Cilento, and R. S. McCuskey. Hepatic microvascular regulatory mechanisms. II. Cholinergic mechanisms. Hepatology Baltimore 2: 230–235, 1982.
 303. Reilly, F. D., R. S. McCuskey, and E. V. Cilento. Hepatic microvascular regulatory mechanisms. I. Adrenergic mechanisms. Microvasc. Res. 21: 103–116, 1981.
 304. Reimann, I. W., U. Klotz, and J. C. Frolich. Effects of cimetidine and ranitidine on steady‐state propranolol kinetics and dynamics. Clin. Pharmacol. Ther. 32: 749–757, 1982.
 305. Richardson, P. D., and D. N. Granger. Microcirculation of the liver and spleen. In: The Physiology and Pharmacology of the Microcirculation, edited by N. A. Mortillaro. Orlando, FL: Academic, 1984, vol. 8, p. 95–131.
 306. Richardson, P. D., and P. G. Withrington. The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog. Br. J. Pharmacol. 57: 93–102, 1976.
 307. Richardson, P. D., and P. G. Withrington. The vasodilator actions of isoprenaline, histamine, prostaglandin E2, glucagon and secretin on the hepatic arterial vascular bed of the dog. Br. J. Pharmacol. 57: 581–588, 1976.
 308. Richardson, P. D., and P. G. Withrington. A comparison of the effects of bradykinin, 5‐hydroxytryptamine and histamine on the hepatic arterial and portal venous vascular beds of the dog: histamine H1 and H2 receptor populations. Br. J. Pharmacol. 60: 123–133, 1977.
 309. Richardson, P. D., and P. G. Withrington. The effects of glucagon, secretin, pancreozymin and pentagastrin on the hepatic arterial vascular bed of the dog. Br. J. Pharmacol. 59: 147–156, 1977.
 310. Richardson, P. D., and P. G. Withrington. The effects of intraportal injections of noradrenaline, adrenaline, vasopressin and angiotensin on the hepatic portal vascular bed of the dog: marked tachyphylaxis to angiotensin. Br. J. Pharmacol. 59: 293–301, 1977.
 311. Richardson, P. D., and P. G. Withrington. Responses of the canine hepatic arterial and portal venous vascular beds to dopamine. Eur. J. Pharmacol. 48: 337–349, 1978.
 312. Richardson, P. D., and P. G. Withrington. Responses of the simultaneously‐perfused hepatic arterial and portal venous vascular beds of the dog to histamine and 5‐hydroxytryptamine. Br. J. Pharmacol. 64: 581–588, 1978.
 313. Richardson, P. D., and P. G. Withrington. Effects of intraportal infusions of hypertonic solutions on hepatic haemodynamics in the dog. J. Physiol. Lond. 301: 82–83, 1979.
 314. Richardson, P. D., and P. G. Withrington. Liver blood flow. I. Intrinsic and nervous control of liver blood flow. Gastroenterology 81: 159–173, 1981.
 315. Richardson, P. D., and P. G. Withrington. Liver blood flow. II. Effects of drugs and hormones on liver blood flow. Gastroenterology 81: 356–375, 1981.
 316. Ricksten, S. E., T. Yao, and P. Thoren. Peripheral and central vascular compliances in conscious normotensive and spontaneously hypertensive rats. Acta Physiol. Scand. 112: 169–177, 1981.
 317. Rosell, S. Neuronal control of microvessels. Annu. Rev. Physiol. 42: 359–371, 1980.
 318. Rothe, C. F. Reflex control of veins and vascular capacitance. Physiol. Rev. 63: 1281–1342, 1983.
 319. Rothe, C. F. Properties of veins. In: Blood Vessels and Lymphatics in Organ Systems, edited by D. I. Abramson and P. B. Dobrin. Orlando, FL: Academic, 1984, p. 85–96.
 320. Rothe, C. F., T. D. Bennett, and B. L. Johns. Linearity of the vascular pressure‐volume relationship of the canine intestine. Circ. Res. 47: 551–558, 1980.
 321. Rothe, C. F., B. L. Johns, and T. D. Bennett. Vascular capacitance of dog intestine using mean transit time of indicator. Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H7–H13, 1978.
 322. Rowell, L. B. Reflex control of regional circulation in humans. J. Auton. Nerv. Syst. 11: 101–114, 1984.
 323. Rowland, M., L. Z. Benet, and G. G. Graham. Clearance concepts in pharmacokinetics. J. Pharmacokinet. Biopharm. 1: 123–136, 1973.
 324. Rowland, M., D. Leitch, G. Fleming, and B. Smith. Protein binding and hepatic clearance: discrimination between models of hepatic clearance with diazepam, a drug of high intrinsic clearance, in the isolated perfused rat liver preparation. J. Pharmacokinet. Biopharm. 12: 129–147, 1984.
 325. Rutlen, D. L., E. W. Supple, and W. J. Powell. The role of the liver in the adrenergic regulation of blood flow from the splanchnic to the central circulation. Yale J. Biol. Med. 52: 99–106, 1979.
 326. Rutlen, D. L., E. W. Supple, and W. J. Powell. Adrenergic regulation of total systemic distensibility. Am. J. Cardiol. 47: 579–588, 1981.
 327. Rutlen, D. L., F. J. Wackers, and B. L. Zaret. Radionuclide assessment of peripheral intravascular capacity: a technique to measure intravascular volume changes in the capacitance circulation in man. Circulation 64: 146–152, 1981.
 328. Sanders, T. M., R. A. Werner, and C. M. Bloor. Visceral blood flow distribution during exercise to exhaustion in conscious dogs. J. Appl. Physiol. 40: 927–931, 1976.
 329. Sarnoff, S. J., J. P. Gilmore, and A. G. Wallace. The influence of autonomic nerve activity on adaptive mechanisms in the heart. In: Nervous Control of the Heart, edited by W. C. Randall Baltimore: Williams and Wilkins, 1965, p. 54–129.
 330. Sato, T., M. Shirataka, N. Ikeda, and F. S. Grodins. Steady‐state systems analysis of hepatic hemodynamics in the isolated perfused canine liver. Am. J. Physiol. 233 (Regulatory Integrative Comp. Physiol. 2): R188–R197, 1977.
 331. Scholtholt, J., and T. Shiraishi. The reaction of liver and intestinal blood flow to a general hypoxia, hypocapnia and hypercapnia in the anesthetized dog. Pfluegers Arch. 318: 185–201, 1970.
 332. Seaman, K., and C. V. Greenway. Hepatic venoconstrictor effects of isoproterenol and nifedipine in anesthetized cats. Can. J. Physiol. Pharmacol. 62: 665–672, 1984.
 333. Seaman, K. L., and C. V. Greenway. Loss of hepatic venous responsiveness after endotoxin in anesthetized cats. Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H658–H663, 1984.
 334. Segstro, R., and C. V. Greenway. Alpha‐adrenoceptor subtypes mediating sympathetic mobilization of blood from the hepatic venous system in anesthetized cats. J. Pharmacol. Exp. Ther. 236: 224–229, 1986.
 335. Segstro, R., K. L. Seaman, I. R. Innes, and C. V. Greenway. Effects of nifedipine on hepatic blood volume in cats: indirect venoconstriction and absence of inhibition of postsynaptic α‐2 adrenoceptor responses. Can. J. Physiol. Pharmacol. 64: 615–620, 1986.
 336. Selkurt, E. E. Comparison of the bromosulphalein method with simultaneous direct hepatic blood flow. Circ. Res. 2: 155–159, 1954.
 337. Shen, E. S., V. F. Garry, and M. W. Anders. Effect of hypoxia on carbon tetrachloride hepatotoxicity. Biochem. Pharmacol. 31: 3787–3793, 1982.
 338. Shoemaker, W. C. Measurement of hepatic blood flow in the unanesthetized dog by a modified bromsulphalein method. J. Appl. Physiol. 15: 473–478, 1960.
 339. Shoukas, A. A. Carotid sinus baroreceptor reflex control and epinephrine. Influence on capacitive and resistive properties of the total pulmonary vascular bed of the dog. Circ. Res. 51: 95–101, 1982.
 340. Shoukas, A. A., and M. C. Brunner. Epinephrine and the carotid sinus baroreceptor reflex. Influence on capacitive and resistive properties of the total systemic vascular bed of the dog. Circ. Res. 47: 249–257, 1980.
 341. Shoukas, A. A., and K. Sagawa. Total systemic vascular compliance measured as incremental volume‐pressure ratio. Circ. Res. 28: 277–289, 1971.
 342. Shoukas, A. A., and K. Sagawa. Control of total systemic vascular capacity by the carotid sinus baroreceptor reflex. Circ. Res. 33: 22–33, 1973.
 343. Slater, G., B. C. Vladeck, R. Bassin, and W. C. Shoemaker. Sequential changes in hepatic blood flows during hemorrhagic shock. Am. J. Physiol. 223: 1428–1432, 1972.
 344. Smiseth, O. A., I. Kingma, D. E. Manyari, E. R. Smith, and J. V. Tyberg. Mechanism of nitroglycerin‐induced blood volume redistribution (Abstract). J. Am. Coll. Cardiol. 5: 553, 1985.
 345. Smiseth, O. A., H. Refsum, and J. V. Tyberg. Pericardial pressure assessed by right atrial pressure: a basis for calculation of left ventricular transmural pressure. Am. Heart J. 108: 603–605, 1984.
 346. Smith, E. R., O. A. Smiseth, I. Kingma, D. Manyari, I. Belenkie, and J. V. Tyberg. Mechanism of action of nitrates. Role of changes in venous capacitance and in the left ventricular diastolic pressure‐volume relations. Am. J. Med. 76: 14–21, 1984.
 347. Stark, R. D. Conductance or resistance? Nature Lond. 217: 779, 1968.
 348. Starling, E. H. On the absorption of fluids from the connective tissue spaces. J. Physiol. Lond. 19: 312–326, 1896.
 349. Stekiel, W. J., J. P. Kampine, E. F. Banaszak, and J. J. Smith. Hepatic clearance of indocyanine in the dog. Am. J. Physiol. 198: 881–885, 1960.
 350. Stella, V. J., K. Yamaoka, and R. H. Levy. An added complication in the estimation of apparent hepatic blood flow in vivo by pharmacokinetic parameters. Drug Metab. Dispos. 9: 172–173, 1981.
 351. Stenson, R. E., R. T. Constantino, and D. C. Harrison. Interrelationships of hepatic blood flow, cardiac output and blood levels of lidocaine in man. Circulation 43: 205–211, 1971.
 352. Stokland, O., M. M. Miller, A. Ilebekk, and F. Kiil. Mechanism of hemodynamic responses to occlusion of the descending thoracic aorta. Am. J. Physiol. 238 (Heart Circ. Physiol. 7): H423–H429, 1980.
 353. Stokland, O., M. Molaug, J. Thorvaldson, A. Ilebekk, and F. Kiil. Cardiac effects of splanchnic and non‐splanchnic blood volume redistribution during aortic occlusions in dogs. Acta Physiol. Scand. 113: 139–146, 1981.
 354. Stokland, O., J. Thorvaldson, A. Ilebekk, and F. Kiil. Contributions of blood drainage from the liver, spleen and intestines to cardiac effects of aortic occlusion in the dog. Acta Physiol. Scand. 114: 351–362, 1982.
 355. Stokland, O., J. Thorvaldson, A. Ilebekk, and F. Kiil. Mechanism of blood pressure elevation during angiotensin infusion. Acta Physiol. Scand. 115: 455–465, 1982.
 356. Supple, E. W., and W. J. Powell. Effect of acetylcholine on vascular capacity in the dog. J. Clin. Invest. 68: 64–74, 1981.
 357. Svensson, C. K., D. J. Edwards, P. M. Mauriello, S. H. Barde, A. C. Foster, R. A. Lanc, E. Middleton, and D. Lalka. Effect of food on hepatic blood flow: implications in the “food effect” phenomenon. Clin. Pharmacol. Ther. 34: 316–323, 1983.
 358. Svensson, C. K., P. M. Mauriello, S. H. Barde, E. Middleton, and D. Lalka. Effect of carbohydrates on estimated hepatic blood flow. Clin. Pharmacol. Ther. 35: 660–665, 1984.
 359. Takeshita, A., and A. L. Mark. Decreased venous distensibility in borderline hypertension. Hypertension Dallas 1: 202–206, 1979.
 360. Teule, G. J., W. Den Hollander, W. Bronsveld, A. Van Lambalgen, G. A. Heidendal, and L. G. Thus. Non‐invasive detection of blood volume redistribution in canine endotoxin shock. Circ. Shock 8: 627–634, 1981.
 361. Teule, G. J., A. Van Lingen, M. A. Verway van Vught, A. D. Rester, R. C. Mackaay, P. D. Bezemer, G. A. Heidendal, and A. D. Thus. Role of peripheral pooling in porcine Escherichia coli sepsis. Circ. Shock 12: 115–123, 1984.
 362. Thomas, W. D., and H. E. Essex. Observations on the hepatic venous circulation with special reference to the sphincteric mechanism. Am. J. Physiol. 158: 303–310, 1949.
 363. Thorvaldson, J., A. Ilebekk, S. Leraand, and F. Kiil. Determinants of pulmonary blood volume. Effects of acute changes in pulmonary vascular pressures and flow. Acta Physiol. Scand. 121: 45–56, 1984.
 364. Thorvaldson, J., O. Stokland, M. Molaug, and A. Ilebekk. Cardiopulmonary blood volume during acute blood pressure elevations in dog. Acta Physiol. Scand. 122: 137–144, 1984.
 365. Tillement, J., G. Houin, R. Zini, S. Urien, E. Albengres, J. Barre, M. Lecomte, P. D'Athis, and B. Sebille. The binding of drugs to blood plasma and macromolecules: recent advances and therapeutic significance. Adv. Drug Res. 13: 59–94, 1984.
 366. Toghill, P. J., and B. N. C. Prichard. A study of the action. of noradrenaline on the splenic red cell pool. Clin. Sci. 26: 203–212, 1964.
 367. Trippodo, N. C., J. Yamamoto, and E. D. Frohlich. Whole‐body venous capacitance and effective total tissue compliance in SHR. Hypertension Dallas 3: 104–112, 1981.
 368. Tyberg, J. V. Ventricular interaction and the pericardium. In: The Ventricle: Basic and Clinical Aspects, edited by H. J. Levine and W. H. Gaasch. Boston: Nijhoff, 1985, p. 171–184.
 369. Tydén, G., H. SamnegÅrd, and L. Thulin. The effects of changes in the carotid sinus baroreceptor activity on splanchnic blood flow in anesthetized man. Acta Physiol. Scand. 106: 187–189, 1979.
 370. Tyden, G., L. Thulin, and B. Nyberg. The effect of cimetidine on liver blood flow in anesthetized man. Acta Chir. Scand. 149: 303–305, 1983.
 371. Tygstrup, N., and K. Winkler. Galactose blood clearance as a measure of hepatic blood flow. Clin. Sci. 17: 1–9, 1958.
 372. Vanecko, R. M., P. B. Szanto, and W. C. Shoemaker. Microcirculatory changes in primate liver during shock. Surg. Gynec. Obstet. 129: 995–1004, 1969.
 373. Vatner, S. F., T. A. Patrick, C. B. Higgins, and D. Franklin. Regional circulatory adjustments to eating and digestion in conscious unrestrained primates. J. Appl. Physiol. 36: 524–529, 1974.
 374. Villeneuve, J. P., G. Pomier, and P. M. Huet. Effect of ethanol on hepatic blood flow in unanesthetized dogs with chronic portal and hepatic vein catheterization. Can. J. Physiol. Pharmacol. 59: 598–603, 1981.
 375. Vorobioff, J., J. E. Bredfeldt, and R. J. Groszmann. Hyperdynamic circulation in portal‐hypertensive rat model: a primary factor for maintenance of chronic portal hypertension. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G52–G57, 1983.
 376. Wade, O. L., B. Combes, A. W. Childs, H. O. Wheeler, A. Cournand, and S. E. Bradley. The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin. Sci. 15: 457–463, 1956.
 377. Wagner, J. G. Relationships among the venous equilibrium (“well‐stirred”) model, the sinusoidal perfusion (“parallel‐tube”) model and a specific two‐compartment open model. Drug Metab. Dispos. 13: 119–120, 1985.
 378. Wagner, J. G., G. J. Szpunar, and J. J. Ferry. Exact mathematical equivalence of the venous equilibrium (“well‐stirred”) model, the sinusoidal perfusion (“parallel‐tube”) model and a specific two‐compartment open model. Drug Metab. Dispos. 12: 385–388, 1984.
 379. Walker, W. F., J. S. MacDonald, and C. Pickard. Hepatic sphincter mechanism in the dog. Br. J. Surg. 48: 218–220, 1960.
 380. Wallentin, I. Importance of tissue pressure for the fluid equilibrium between che vascular and interstitial compartments in the small intestine. Acta Physiol. Scand. 68: 304–315, 1966.
 381. Wanner, A., R. Begin, M. Cohn, and M. A. Sackner. Vascular volumes of the pulmonary circulation in intact dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 956–963, 1978.
 382. Wathen, C. G., W. J. Hannan, C. J. Adie, and A. L. Muir. A radionuclide method for the simultaneous study of the effects of drugs on central and peripheral haemodynamics. Br. J. Clin. Pharmacol. 16: 45–50, 1983.
 383. Weigand, B. D., S. G. Ketterer, and E. Rapaport. The use of indocyanine green for the evaluation of hepatic function and blood flow in man. Am. J. Digest. Dis. 5: 427–436, 1960.
 384. Weisiger, R., J. Gollan, and R. Ockner. Receptors for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin‐bound substances. Science Wash. DC 211: 1048–1051, 1981.
 385. Wheeler, H. O., R. M. Epstein, R. R. Robinson, and E. S. Snell. Hepatic storage and excretion of sulfobromophthalein sodium in the dog. J. Clin. Invest. 39: 236–247, 1960.
 386. Whitsett, T. L., P. G. Dayton, and J. L. McNay. The effect of hepatic blood flow on the hepatic removal rate of oxyphenbutazone in the dog. J. Pharmacol. Exp. Ther. 177: 246–255, 1971.
 387. Wilkinson, G. R., and D. G. Shand. A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18: 377–390, 1975.
 388. Winkler, K., J. A. Larsen, T. Munkner, and N. Tygstrup. Determination of the hepatic blood flow in man by simultaneous use of five test substances measured in two parts of the liver. Scand. J. Clin. Lab. Invest. 17: 423–432, 1965.
 389. Yamaguchi, N., and D. Garceau. Correlations between hemodynamic parameters of the liver and norepinephrine release upon hepatic nerve stimulation in the dog. Can. J. Physiol. Pharmacol. 58: 1347–1355, 1980.
 390. Yamamoto, J., N. C. Trippodo, A. A. MacPhee, and E. D. Frohlich. Decreased total venous capacity in Goldblatt hypertensive rats. Am. J. Physiol. 240 (Heart Circ. Physiol. 9): H487–H492, 1981.
 391. Yamamoto, K., I. Sherman, J. M. Phillips, and M. M. Fisher. Three‐dimensional observations of the hepatic arterial terminations in rat, hamster and human liver by scanning electron microscopy of microvascular casts. Hepatology Baltimore 5: 452–456, 1985.
 392. Yeager, V. L., D. J. Anderson, and J. J. Taylor. Smooth muscle in the hepatic artery, portal vein and hepatic vein within the liver of the raccoon and guinea pig. Experientia 41: 262–265, 1985.
 393. Yoffey, J. M., and F. C. Courtice. Lymphatics, Lymph and the Lymphomyeloid Complex. New York: Academic, 1970, p. 206–320.
 394. Zimpfer, M., W. T. Manders, A. C. Barger, and S. F. Vatner. Pentobarbital alters compensatory neural and humoral mechanisms in response to hemorrhage. Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H713–H721, 1982.
 395. Zink, J., and C. V. Greenway. Control of ascites absorption in anesthetized cats: effects of intraperitoneal pressure, protein and furosemide diuresis. Gastroenterology 73: 1119–1124, 1977.
 396. Zink, J., and C. V. Greenway. Intraperitoneal pressure in formation and reabsorption of ascites in cats. Am. J. Physiol. 233 (Heart Circ. Physiol. 2): H185–H190, 1977.

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Clive V. Greenway, W. Wayne Lautt. Hepatic circulation. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 1519-1564. First published in print 1989. doi: 10.1002/cphy.cp060141