Comprehensive Physiology Wiley Online Library

Gastrointestinal blood flow‐measuring techniques

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Microsphere Technique
1.1 Principle of Measurement
1.2 Fractionation of Intramural Blood Flow in Intestine
1.3 Microsphere Studies in Gastric Circulation
2 Laser‐Doppler Velocimetry
2.1 History
2.2 Theory of Laser‐Doppler Blood Flowmetry
2.3 Evaluations in Gastrointestinal Tract
3 Aminopyrine Clearance and Other pH Trapping Techniques
3.1 Overview of pH Trapping Methods
3.2 Theoretical Background
3.3 Evaluation of Aminopyrine Clearance
4 Hydrogen Clearance
4.1 History
4.2 Principle of Measurement
4.3 Advantages and Disadvantages of Hydrogen Clearance
4.4 Locally Generated Hydrogen
5 Conclusions
Figure 1. Figure 1.

Size of microspheres determines their distribution within gut wall. Shown are percentages of each microsphere size (X) recovered in canine mucosa, submucosa, muscularis, and venous blood. Note reciprocal relation between mucosal and submucosal trapping of spheres.

From Maxwell et al.
Figure 2. Figure 2.

Size‐selective microsphere trapping in intestine. Shown is ratio of frequency of given sphere size in tissue sample to its frequency in injectate or among all spheres recovered. This ratio would be unity if sphere trapping were not size dependent.

From Maxwell et al.
Figure 3. Figure 3.

Microsphere migration induced by vasodilation. Mucosa‐to‐submucosal ratios of sphere deposition were increased by vasodilation with isoproterenol (no data points fell below line of identity). For both microsphere sizes, control and experimental data were significantly different.

From Maxwell et al.
Figure 4. Figure 4.

Microsphere sieving effect. Relative frequency distributions of injected spheres (filled square) and spheres recovered from venous blood (x). Injectate was mixture of commercial 9‐, 10‐, 15‐, and 20‐μm spheres.

From Maxwell et al.
Figure 5. Figure 5.

Predicted (+) and observed (x) relative frequency distributions of spheres recovered from venous blood. Injectate same as in Fig. . Assumptions in model were that microsphere delivery to capillaries was r4 function of capillary radius, that mean capillary diameter was 7.38 μm ± SD 1.4, and that frequency distribution was lognormal.

From Maxwell et al.
Figure 6. Figure 6.

Relative frequency distribution of intestinal capillary diameters . Frequency distribution calculated from injected and venous microsphere populations without assumptions regarding mathematical form of frequency distribution of intestinal capillary diameters.

From McMahan et al.
Figure 7. Figure 7.

Spatial distribution of microspheres within stomach wall. Deposition of spheres in gastric pits was inversely related to microsphere size, whereas their accumulation in lamina propria was directly proportional to sphere diameter.

Adapted from Varhaug et al.
Figure 8. Figure 8.

Doppler effect for sound waves. A: if both listener and sound source are stationary, listener hears Ct/Λ waves in t seconds, where C is speed of sound and Λ is wavelength. B: if listener moves toward source at velocity vL, he will hear additional vLt/Λ waves in time t.

Adapted from Magnin
Figure 9. Figure 9.

Typical optics for laser‐Doppler velocimetry in tissue. A: coherent light is guided to tissue surface by optical fiber, and one or more receiving fibers return light scattered by tissue to photo‐detector. B: depth or volume of tissue from which scattered photons are collected increases with greater separation between sending and receiving fibers.

Figure 10. Figure 10.

Interactions between photons and tissue. A: of photons returning to photodetector, most have been scattered by static tissue elements. B: a few photons have experienced a Doppler shift as a result of a single collision with a moving red blood cell. C: other photons experience multiple scattering by moving erythrocytes, but these events are infrequent except in large vessels.

Adapted from Bonner and Nossal
Figure 11. Figure 11.

Doppler frequency spectra recorded from canine intestinal mucosa. In absence of blood flow (artery occluded), instrument noise, imperceptible tissue motion, and unknown factors produce frequency shift in laser light. Average frequency is increased during control blood flow and increased still further during reactive hyperemia

A. P. Shepherd, G. L. Riedel, and J. W. Kiel, unpublished observations
Figure 12. Figure 12.

Idealized scheme of laser‐Doppler signal processing. Light returning from tissue consists chiefly of unshifted photons scattered by static tissue and a few Doppler‐shifted photons scattered by moving red blood cells. Thus, as the photons mix, a photodetector signal results that has a direct current (DC) offset and a superimposed alternating current (AC) component. A: signal for a single red cell moving at constant velocity. B: if more red cells were moving at same velocity, magnitude of AC component would increase as more photons are Doppler shifted. C: if other factors remained constant and red cell velocity increased, frequency (f) of signal would increase.

From Haumschild Reprinted by permission. Copyright © Instrument Society of America 1986. From Biomedical Sciences Instrumentation, vol. 22
Figure 13. Figure 13.

Block diagram of microprocessor‐based laser‐Doppler blood flowmeter. Typical signal processing includes setting upper and lower frequency cutoff filters to maximize signal‐to‐noise ratio and calculations of relative red blood cell flux, local red cell concentration in tissue, and average red cell velocity.

Figure 14. Figure 14.

Linearity of laser‐Doppler blood flowmeter in intestine. Left: in isolated canine small bowel, raw laser‐Doppler velocimetry measurements were linearly related to total blood flow (r = 0.89). Right: normalizing data to flow values measured at perfusion pressure of 120 mmHg improved correlation (slope, 1.1; r = 0.97). Preparations were vasodilated with isoproterenol to eliminate autoregulation and unpredictable redistributions of blood flow.

From Shepherd and Riedel
Figure 15. Figure 15.

Linearity of laser‐Doppler velocimetric (LDV) measurements of gastric mucosal blood flow. Top: in chambered canine stomach flaps vasodilated with isoproterenol, LDV‐measured blood flow was linearly related to total gastric perfusion (r = 0.98). Flow was changed by altering perfusion pressure. Bottom: in preparations not vasodilated with isoproterenol, curve deviated from apparent linearity because gastric mucosal blood flow was autoregulated, as indicated by analysis of pressure versus flow relationship (not shown). For comparison, regression line from isoproterenol data is also shown.

From Kiel et al.
Figure 16. Figure 16.

Lack of reproducibility with laser‐Doppler blood flowmetry. Manipulating portal venous perfusion pressure to alter blood flow to isolated rat liver preparation resulted in highly linear relation between total hepatic perfusion and laser‐Doppler velocimetry‐measured blood on liver surface, but slopes of lines were not consistently reproducible.

From Shepherd et al.
Figure 17. Figure 17.

Reactive hyperemia and motility artifacts in laser‐Doppler blood flow tracings. In isolated loop of canine small bowel, spikes in laser‐Doppler velocimetry tracings during arterial occlusion are motility artifacts. Both mucosal and muscularis perfusion seem to undergo motility‐related oscillations (also see Fig. ). Note that following arterial occlusion both total and mucosal blood flow tracings displayed characteristic reactive hyperemia, but reactive hyperemia was absent in muscularis.

From Shepherd and Riedel
Figure 18. Figure 18.

Motility artifacts or motility‐related oscillations in gastric blood flow? In chambered canine stomach flaps, laser‐Doppler blood flow tracings oscillate at same frequency as electrical activity in muscularis.

From Kiel et al.
Figure 19. Figure 19.

Two‐compartment model of the pH partition hypothesis. Gastric mucosa is represented as a plasma compartment and a gastric juice compartment separated by a lipoidal barrier selectively permeable to undissociated weak base. At plasma pH, weak base is predominantly undissociated, readily diffuses across barrier, and is “trapped” when dissociated in the low pH of gastric juice.

Figure 20. Figure 20.

Dissociation of gastric secretion and aminopyrine clearance. In a histamine‐stimulated Heidenhain pouch, a low dose of isoproterenol greatly increased aminopyrine clearance but did not change gastric volume secretion. However, the higher dose depressed both aminopyrine clearance and gastric secretion. R, concentration ratio.

Adapted from Jacobson et al.
Figure 21. Figure 21.

Dissociation of total gastric blood flow and aminopyrine clearance during stimulated acid secretion. In Heidenhain pouch, graded gastrin infusion greatly increased aminopyrine clearance without changing total blood flow.

Adapted from Swan and Jacobson
Figure 22. Figure 22.

Dissociation of total gastric blood flow and aminopyrine clearance during inhibition of acid secretion. In chambered canine stomach flap stimulated with histamine, thiocyanate poisoning greatly depressed aminopyrine clearance and secretion of gastric juice but did not alter total blood flow.

Adapted from Moody
Figure 23. Figure 23.

Dissociation of gastric oxygen consumption and aminopyrine clearance during inhibition of acid secretion. In chambered canine stomach flap stimulated with histamine, thiocyanate poisoning depressed aminopyrine clearance nearly to zero without altering either total blood flow or gastric oxygen uptake.

Adapted from Moody
Figure 24. Figure 24.

Comparison of gastric mucosal blood flow measurements by aminopyrine clearance and microspheres. During infusions of histamine or isoproterenol, aminopyrine clearance values showed significant linear correlation with microsphere determinations in chambered canine stomach flaps. However, slopes of regression lines show that aminopyrine clearance consistently underestimated blood flow measured by microspheres. Furthermore discrepancy between the two methods was even greater in the absence of acid secretion (isoproterenol). Linear regression lines are shown; data points omitted for clarity.

Adapted from Archibald et al.
Figure 25. Figure 25.

Effect of acid secretion rate on ratio of microsphere‐measured mucosal blood flow to aminopyrine clearance (MMF/APC). If two techniques measured same quantity, ratio would equal one. Most data points lie above solid line showing aminopyrine clearance underestimated microsphere determinations. Note disparity increased markedly at low rates of acid secretion.

Adapted from Archibald et al.
Figure 26. Figure 26.

Comparison of aminopyrine clearances determined spectrophotometrically and with 14C‐labeled aminopyrine. Although measurements were highly correlated, slope of regression line, which is significantly different from 1.0, indicates that spectrophotometric method overestimated [14C]aminopyrine clearance. Spectrophotometric method requires much higher plasma concentrations of aminopyrine than isotope method.

Data from Tague and Jacobson
Figure 27. Figure 27.

Aminopyrine clearance overestimates gastric mucosal blood flow during stimulated acid secretion. In rabbits, pentagastrin increased blood flow measured by all 3 techniques. Measurements by electromagnetic flow probe and hydrogen clearance showed similar increases in blood flow (17% and 22%, respectively), but an inordinate increase in aminopyrine clearance (216%) occurred that was quantitatively inconsistent with the other two measurements. Flow units are left gastric artery, ml/min; aminopyrine and hydrogen clearance, ml · min−1 · 100 g−1.

Data from Leung et al.
Figure 28. Figure 28.

Sequestration of aminopyrine by isolated parietal cells. Parietal cells accumulate significant quantities of aminopyrine; this sequestration is enhanced by agents listed.

Adapted from Sonnenberg et al.
Figure 29. Figure 29.

Hydrogen gas clearance values significantly correlated with microsphere‐measured gastric mucosal blood flow. In anterior corpus of canine stomach at gastrotomy, hydrogen underestimated microsphere‐measured gastric mucosal perfusion as indicated by slope of regression line.

From Ashley and Cheung
Figure 30. Figure 30.

Principle of hydrogen clearance technique for measuring blood flow. If instantaneous arterial (Cin) and venous (Cout) concentrations of indicator gas were known, blood flow could be determined from either tissue uptake or washout of hydrogen, but in practice only relative tissue hydrogen concentration is recorded. Also see Figs. and .

Figure 31. Figure 31.

Blood flow determined from tissue saturation or uptake of indicator. Blood flow could be determined from tissue uptake of hydrogen if instantaneous arterial (Cin) and venous (Cout) concentrations of hydrogen were known.

Figure 32. Figure 32.

Blood flow determined from washout of hydrogen. If it can be assumed that hydrogen reaches equilibrium with tissue (C∞), blood flow can be determined by monitoring only instantaneous tissue hydrogen concentration and integrating area under washout curve.

Figure 33. Figure 33.

FIG. 33. Proposed method for measuring blood flow by local generation of hydrogen. One electrode measures local H2 concentration while a second electrode connected to a constant current source generates hydrogen electrochemically. Tissue is first saturated with hydrogen, then H2‐generating current is shut off, and washout curve is recorded.



Figure 1.

Size of microspheres determines their distribution within gut wall. Shown are percentages of each microsphere size (X) recovered in canine mucosa, submucosa, muscularis, and venous blood. Note reciprocal relation between mucosal and submucosal trapping of spheres.

From Maxwell et al.


Figure 2.

Size‐selective microsphere trapping in intestine. Shown is ratio of frequency of given sphere size in tissue sample to its frequency in injectate or among all spheres recovered. This ratio would be unity if sphere trapping were not size dependent.

From Maxwell et al.


Figure 3.

Microsphere migration induced by vasodilation. Mucosa‐to‐submucosal ratios of sphere deposition were increased by vasodilation with isoproterenol (no data points fell below line of identity). For both microsphere sizes, control and experimental data were significantly different.

From Maxwell et al.


Figure 4.

Microsphere sieving effect. Relative frequency distributions of injected spheres (filled square) and spheres recovered from venous blood (x). Injectate was mixture of commercial 9‐, 10‐, 15‐, and 20‐μm spheres.

From Maxwell et al.


Figure 5.

Predicted (+) and observed (x) relative frequency distributions of spheres recovered from venous blood. Injectate same as in Fig. . Assumptions in model were that microsphere delivery to capillaries was r4 function of capillary radius, that mean capillary diameter was 7.38 μm ± SD 1.4, and that frequency distribution was lognormal.

From Maxwell et al.


Figure 6.

Relative frequency distribution of intestinal capillary diameters . Frequency distribution calculated from injected and venous microsphere populations without assumptions regarding mathematical form of frequency distribution of intestinal capillary diameters.

From McMahan et al.


Figure 7.

Spatial distribution of microspheres within stomach wall. Deposition of spheres in gastric pits was inversely related to microsphere size, whereas their accumulation in lamina propria was directly proportional to sphere diameter.

Adapted from Varhaug et al.


Figure 8.

Doppler effect for sound waves. A: if both listener and sound source are stationary, listener hears Ct/Λ waves in t seconds, where C is speed of sound and Λ is wavelength. B: if listener moves toward source at velocity vL, he will hear additional vLt/Λ waves in time t.

Adapted from Magnin


Figure 9.

Typical optics for laser‐Doppler velocimetry in tissue. A: coherent light is guided to tissue surface by optical fiber, and one or more receiving fibers return light scattered by tissue to photo‐detector. B: depth or volume of tissue from which scattered photons are collected increases with greater separation between sending and receiving fibers.



Figure 10.

Interactions between photons and tissue. A: of photons returning to photodetector, most have been scattered by static tissue elements. B: a few photons have experienced a Doppler shift as a result of a single collision with a moving red blood cell. C: other photons experience multiple scattering by moving erythrocytes, but these events are infrequent except in large vessels.

Adapted from Bonner and Nossal


Figure 11.

Doppler frequency spectra recorded from canine intestinal mucosa. In absence of blood flow (artery occluded), instrument noise, imperceptible tissue motion, and unknown factors produce frequency shift in laser light. Average frequency is increased during control blood flow and increased still further during reactive hyperemia

A. P. Shepherd, G. L. Riedel, and J. W. Kiel, unpublished observations


Figure 12.

Idealized scheme of laser‐Doppler signal processing. Light returning from tissue consists chiefly of unshifted photons scattered by static tissue and a few Doppler‐shifted photons scattered by moving red blood cells. Thus, as the photons mix, a photodetector signal results that has a direct current (DC) offset and a superimposed alternating current (AC) component. A: signal for a single red cell moving at constant velocity. B: if more red cells were moving at same velocity, magnitude of AC component would increase as more photons are Doppler shifted. C: if other factors remained constant and red cell velocity increased, frequency (f) of signal would increase.

From Haumschild Reprinted by permission. Copyright © Instrument Society of America 1986. From Biomedical Sciences Instrumentation, vol. 22


Figure 13.

Block diagram of microprocessor‐based laser‐Doppler blood flowmeter. Typical signal processing includes setting upper and lower frequency cutoff filters to maximize signal‐to‐noise ratio and calculations of relative red blood cell flux, local red cell concentration in tissue, and average red cell velocity.



Figure 14.

Linearity of laser‐Doppler blood flowmeter in intestine. Left: in isolated canine small bowel, raw laser‐Doppler velocimetry measurements were linearly related to total blood flow (r = 0.89). Right: normalizing data to flow values measured at perfusion pressure of 120 mmHg improved correlation (slope, 1.1; r = 0.97). Preparations were vasodilated with isoproterenol to eliminate autoregulation and unpredictable redistributions of blood flow.

From Shepherd and Riedel


Figure 15.

Linearity of laser‐Doppler velocimetric (LDV) measurements of gastric mucosal blood flow. Top: in chambered canine stomach flaps vasodilated with isoproterenol, LDV‐measured blood flow was linearly related to total gastric perfusion (r = 0.98). Flow was changed by altering perfusion pressure. Bottom: in preparations not vasodilated with isoproterenol, curve deviated from apparent linearity because gastric mucosal blood flow was autoregulated, as indicated by analysis of pressure versus flow relationship (not shown). For comparison, regression line from isoproterenol data is also shown.

From Kiel et al.


Figure 16.

Lack of reproducibility with laser‐Doppler blood flowmetry. Manipulating portal venous perfusion pressure to alter blood flow to isolated rat liver preparation resulted in highly linear relation between total hepatic perfusion and laser‐Doppler velocimetry‐measured blood on liver surface, but slopes of lines were not consistently reproducible.

From Shepherd et al.


Figure 17.

Reactive hyperemia and motility artifacts in laser‐Doppler blood flow tracings. In isolated loop of canine small bowel, spikes in laser‐Doppler velocimetry tracings during arterial occlusion are motility artifacts. Both mucosal and muscularis perfusion seem to undergo motility‐related oscillations (also see Fig. ). Note that following arterial occlusion both total and mucosal blood flow tracings displayed characteristic reactive hyperemia, but reactive hyperemia was absent in muscularis.

From Shepherd and Riedel


Figure 18.

Motility artifacts or motility‐related oscillations in gastric blood flow? In chambered canine stomach flaps, laser‐Doppler blood flow tracings oscillate at same frequency as electrical activity in muscularis.

From Kiel et al.


Figure 19.

Two‐compartment model of the pH partition hypothesis. Gastric mucosa is represented as a plasma compartment and a gastric juice compartment separated by a lipoidal barrier selectively permeable to undissociated weak base. At plasma pH, weak base is predominantly undissociated, readily diffuses across barrier, and is “trapped” when dissociated in the low pH of gastric juice.



Figure 20.

Dissociation of gastric secretion and aminopyrine clearance. In a histamine‐stimulated Heidenhain pouch, a low dose of isoproterenol greatly increased aminopyrine clearance but did not change gastric volume secretion. However, the higher dose depressed both aminopyrine clearance and gastric secretion. R, concentration ratio.

Adapted from Jacobson et al.


Figure 21.

Dissociation of total gastric blood flow and aminopyrine clearance during stimulated acid secretion. In Heidenhain pouch, graded gastrin infusion greatly increased aminopyrine clearance without changing total blood flow.

Adapted from Swan and Jacobson


Figure 22.

Dissociation of total gastric blood flow and aminopyrine clearance during inhibition of acid secretion. In chambered canine stomach flap stimulated with histamine, thiocyanate poisoning greatly depressed aminopyrine clearance and secretion of gastric juice but did not alter total blood flow.

Adapted from Moody


Figure 23.

Dissociation of gastric oxygen consumption and aminopyrine clearance during inhibition of acid secretion. In chambered canine stomach flap stimulated with histamine, thiocyanate poisoning depressed aminopyrine clearance nearly to zero without altering either total blood flow or gastric oxygen uptake.

Adapted from Moody


Figure 24.

Comparison of gastric mucosal blood flow measurements by aminopyrine clearance and microspheres. During infusions of histamine or isoproterenol, aminopyrine clearance values showed significant linear correlation with microsphere determinations in chambered canine stomach flaps. However, slopes of regression lines show that aminopyrine clearance consistently underestimated blood flow measured by microspheres. Furthermore discrepancy between the two methods was even greater in the absence of acid secretion (isoproterenol). Linear regression lines are shown; data points omitted for clarity.

Adapted from Archibald et al.


Figure 25.

Effect of acid secretion rate on ratio of microsphere‐measured mucosal blood flow to aminopyrine clearance (MMF/APC). If two techniques measured same quantity, ratio would equal one. Most data points lie above solid line showing aminopyrine clearance underestimated microsphere determinations. Note disparity increased markedly at low rates of acid secretion.

Adapted from Archibald et al.


Figure 26.

Comparison of aminopyrine clearances determined spectrophotometrically and with 14C‐labeled aminopyrine. Although measurements were highly correlated, slope of regression line, which is significantly different from 1.0, indicates that spectrophotometric method overestimated [14C]aminopyrine clearance. Spectrophotometric method requires much higher plasma concentrations of aminopyrine than isotope method.

Data from Tague and Jacobson


Figure 27.

Aminopyrine clearance overestimates gastric mucosal blood flow during stimulated acid secretion. In rabbits, pentagastrin increased blood flow measured by all 3 techniques. Measurements by electromagnetic flow probe and hydrogen clearance showed similar increases in blood flow (17% and 22%, respectively), but an inordinate increase in aminopyrine clearance (216%) occurred that was quantitatively inconsistent with the other two measurements. Flow units are left gastric artery, ml/min; aminopyrine and hydrogen clearance, ml · min−1 · 100 g−1.

Data from Leung et al.


Figure 28.

Sequestration of aminopyrine by isolated parietal cells. Parietal cells accumulate significant quantities of aminopyrine; this sequestration is enhanced by agents listed.

Adapted from Sonnenberg et al.


Figure 29.

Hydrogen gas clearance values significantly correlated with microsphere‐measured gastric mucosal blood flow. In anterior corpus of canine stomach at gastrotomy, hydrogen underestimated microsphere‐measured gastric mucosal perfusion as indicated by slope of regression line.

From Ashley and Cheung


Figure 30.

Principle of hydrogen clearance technique for measuring blood flow. If instantaneous arterial (Cin) and venous (Cout) concentrations of indicator gas were known, blood flow could be determined from either tissue uptake or washout of hydrogen, but in practice only relative tissue hydrogen concentration is recorded. Also see Figs. and .



Figure 31.

Blood flow determined from tissue saturation or uptake of indicator. Blood flow could be determined from tissue uptake of hydrogen if instantaneous arterial (Cin) and venous (Cout) concentrations of hydrogen were known.



Figure 32.

Blood flow determined from washout of hydrogen. If it can be assumed that hydrogen reaches equilibrium with tissue (C∞), blood flow can be determined by monitoring only instantaneous tissue hydrogen concentration and integrating area under washout curve.



Figure 33.

FIG. 33. Proposed method for measuring blood flow by local generation of hydrogen. One electrode measures local H2 concentration while a second electrode connected to a constant current source generates hydrogen electrochemically. Tissue is first saturated with hydrogen, then H2‐generating current is shut off, and washout curve is recorded.

References
 1. Ahn, H., J. Lindhagen, G. E. Nilsson, E. G. Salerud, M. Jodal, and O. Lundgren. Evaluation of laser‐Doppler flow‐metry in the assessment of intestinal blood flow in cat. Gastroenterology 88: 951–957, 1985.
 2. Archibald, L. H., F. G. Moody, and M. Simons. Effect of isoproterenol on canine gastric acid secretion and blood flow. Surg. Forum. 25: 409–411, 1974.
 3. Archibald, L. H., F. G. Moody, and M. A. Simons. Comparison of gastric mucosal blood flow as determined by aminopyrine clearance and gamma‐labeled microspheres. Gastroenterology 69: 630–635, 1975.
 4. Archibald, L. H., F. G. Moody, and M. Simons. Measurement of gastric blood flow with radioactive microspheres. J. Appl. Physiol. 38: 1051–1056, 1975.
 5. Ashley, S. W., and L. Y. Cheung. Measurement of gastric mucosal blood flow by hydrogen gas clearance. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G339–G345, 1984.
 6. Ashley, S. W., Z. Y. Yan, D. I. Soybel, and L. Y. Cheung. Endoscopic measurements of gastric mucosal blood flow in dogs. J. Surg. Res. 38: 416–423, 1985.
 7. Aukland, K. Hydrogen polarography in measurement of local blood flow, theoretical and empirical basis. Acta Neurol. Scand. 41, Suppl. 14: 42–45, 1965.
 8. Aukland, K., B. F. Bower, and R. W. Berliner. Measurement of local blood flow with hydrogen gas. Circ. Res. 14: 164–187, 1964.
 9. Bankir, L. M., T. T. Tan, and J. Grunfeld. Measurement of glomerular blood flow in rabbits and rats: erroneous findings with 15‐μm microspheres. Kidney Int. 15: 126–133, 1979.
 10. Bassingthwaighte, J. B., T. Yipintsoi, and R. B. Harvey. Microvasculature of the dog left ventricular myocardium. Microvasc. Res. 7: 229–249, 1974.
 11. Berglindh, T., H. F. Helander, and K. J. Öbrink. Effects of secretagogues on oxygen consumption, aminopyrine accumulation and morphology in isolated gastric glands. Acta Physiol. Scand. 97: 401–414, 1976.
 12. Berglindh, T., and K. J. Öbrink. A method for preparing isolated glands from the rabbit gastric mucosa. Acta Physiol. Scand. 96: 150–159, 1976.
 13. Bharadvaj, B. K., R. F. Mabon, and D. P. Giddens. Steady flow in a model of the human carotid bifurcation. Part II—laser‐Doppler anemometer measurements. J. Biochem. 15: 363–378, 1982.
 14. Biber, B., O. Lundgren, and J. Svanvik. The influence of blood flow on the rate of absorption of 85Kr from the small intestine of the cat. Acta Physiol. Scand. 89: 227–238, 1973.
 15. Bond, J. H., and M. D. Levitt. Use of microspheres to measure small intestinal villus blood flow in the dog. Am. J. Physiol. 236 (Endocrinol. Metab. Gastrointest. Physiol. 5): E577–E583, 1979.
 16. Bonner, R. F., and R. Nossal. A model for laser Doppler measurements of blood flow in tissue. Appl. Opt. 20: 2097–2107, 1981.
 17. Bonner, R. F., T. R. Clem, P. D. Bowen, and R. L. Bowman. Laser‐Doppler continuous real‐time monitor of pulsatile and mean blood flow in tissue microcirculation. In: Scattering Techniques Applied to Supramolecular and Non‐Equilibrium Systems, edited by S. H. Chen, B. Chu, and R. Nossal. New York: Plenum, 1981, p. 685–702.
 18. Born, G. V. R., A. Melling, and J. H. Whitelaw. Laser Doppler microscope for blood velocity measurements. Biorheology 15: 163–172, 1978.
 19. Brodie, B. B., and J. Axelrod. The fate of aminopyrine (pyramidon) in man and methods for the estimation of aminopyrine and its metabolites in biological material. J. Pharmacol. Exp. Ther. 99: 171–184, 1950.
 20. Buckberg, G. D., J. C. Luck, D. B. Payne, J. I. E. Hoffman, J. P. Archie, and D. E. Fixler. Some sources of error in measuring regional blood flow with radioactive microspheres. J. Appl. Physiol. 31: 598–604, 1971.
 21. Cheung, L. Y., F. G. Moody, and R. S. Reese. Effect of aspirin, bile salt, and ethanol on canine gastric mucosal blood flow. Surgery St. Louis 77: 786–792, 1975.
 22. Cheung, L. Y., and L. A. Sonnenschein. Measurement of regional gastric mucosal blood flow by hydrogen gas clearance. Am. J. Surg. 147: 32–37, 1984.
 23. Chou, C. C., C. P. Hsieh, Y. M. Yu, P. Kvietys, L. C. Yu, R. Pittman, and J. M. Dabney. Localization of mesenteric hyperemia during digestion in dogs. Am. J. Physiol. 230: 583–589, 1976.
 24. Clark, L. C.Jr., and L. M. Bargeron. Left to right shunt detection by an intravascular electrode with hydrogen as an indicator. Science Wash. DC 130: 709–710, 1959.
 25. Clark, L. C.Jr., and L. M. Bargeron. Detection and direct recording of right to left shunts with a hydrogen electrode catheter. Surgery St. Louis 46: 797–804, 1959.
 26. Clausen, G., A. Kirkebo, I. Tyssebotn, E. S. Ofjord, and K. Aukland. Erroneous estimates of intrarenal blood flow distribution in the dog with radiolabelled microspheres. Acta Physiol. Scand. 107: 385–387, 1979.
 27. Cowley, D. J., and C. F. Code. Effects of secretory inhibitors on mucosal blood flow in nonsecreting stomach of conscious dogs. Am. J. Physiol. 218: 270–274, 1970.
 28. Delaney, J. P., and E. Grim. Canine gastric blood flow and its distribution. Am. J. Physiol. 207: 1195–1202, 1964.
 29. Delaney, J. P., and E. Grim. Experimentally induced variations in canine gastric blood flow and its distribution. Am. J. Physiol. 208: 353–358, 1965.
 30. Dinda, P. K., M. G. Buell, L. R. DaCosta, and I. T. Beck. Simultaneous estimation of arteriolar, capillary, and shunt blood flow of the gut mucosa. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G29–G37, 1983.
 31. DiResta, G. R. The Measurement of Tissue Perfusion Using a H2‐Clamp Technique. Brooklyn, NY: Polytechnic Inst. of New York, 1982 Dissertation. (Dissertation Abstracts Order #DA8217322.).
 32. Domenech, R. J., J. I. E. Hoffman, M. I. M. Noble, K. B. Saunders, J. R. Henson, and S. Subijanto.. Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs. Circ. Res. 25: 581–596, 1969.
 33. Druce, H. M., R. F. Bonner, C. Patow, P. Choo, R. J. Summers, and M. A. Kaliner. Response of nasal blood flow to neurohormones as measured by laser‐Doppler velocimetry. J. Appl. Physiol. 57: 1276–1283, 1984.
 34. Duteil, L., J. C. Bernengo, and W. Schalla. A double wavelength laser‐Doppler system to investigate skin microcirculation. IEEE Trans. Biomed. Eng. 32: 439–447, 1985.
 35. Edlich, R. F., I. Grotenhuis, and R. J. Buchin. Radioactive microspheres. Effect of their physical properties on vascular distribution. Proc. Soc. Exp. Biol. Med. 128: 909–913, 1968.
 36. Einav, S., H. J. Berman, R. L. Fuhro, P. R. Digiovanni, J. D. Fridman, and S. Fine. Measurement of blood flow in vivo by laser Doppler anemometry through a microscope. Biorheology 12: 203–205, 1975.
 37. Fan, F., G. B. Schuessler, R. Y. Z. Chen, and S. Chien. Determinations of blood flow and shunting of 9‐ and 15‐μm spheres in regional beds. Am. J. Physiol. 237 (Heart Circ. Physiol. 6): H25–H33, 1979.
 38. Gannon, B. J., R. W. Gore, and P. A. W. Rogers. Is there an anatomical basis for a vascular counter‐current mechanism in rabbit and human intestinal villi? Biomed. Res. 2: 235–241, 1981.
 39. Granger, D. N., and G. B. Bulkley. Measurement of Blood Flow. Applications to the Splanchnic Circulation. Baltimore, MD: Williams & Wilkins, 1981.
 40. Granger, D. N., J. D. Valleau, R. E. Parker, R. S. Lane, and A. E. Taylor. Effects of adenosine on intestinal hemodynamics, oxygen delivery, and capillary fluid exchange. Am. J. Physiol. 235 (Heart Circ. Physiol. 4): H707–H719, 1978.
 41. Greenway, C. V., and V. S. Murthy. Effects of vasopressin and isoprenaline infusions on the distribution of blood flow in the intestine; criteria for the validity of microsphere studies. Br. J. Pharmacol. 46: 177–188, 1972.
 42. Grim, E., and E. O. Lindseth. Distribution of blood flow to the tissues of the small intestine of the dog. Med. Bull. Univ. Minn. 30: 138–145, 1958.
 43. Gush, R. J., T. A. King, and M. I. V. Jayson. Aspects of laser light scattering from skin tissue with application to laser Doppler blood flow measurement. Phys. Med. Biol. 29: 1463–1476, 1984.
 44. Guth, P. H., H. Baumann, M. I. Grossman, D. Aures, and J. Elashoff. Measurement of gastric mucosal blood flow in man. Gastroenterology 74: 831–834, 1978.
 45. Hales, J. R. S., A. A. Fawcett, and J. W. Bennet. Differential influences of CNS and superficial body temperatures on the partition of cutaneous blood flow between capillaries and arteriovenous anastomoses (AVA's). Pfluegers Arch. 361: 105–106, 1975.
 46. Harper, A. A., J. D. Reed, and J. R. Smy. Gastric blood flow in anaesthetized cats. J. Physiol. Lond. 194: 795–807, 1968.
 47. Haumschild, D. J. An overview of laser Doppler flowmetry. In: Biomedical Sciences Instrumentation, Proc. 23rd Annual Rocky Mountain Bioengineering Symp. and 23rd Int. ISA Biomedical Sciences Instrumentation Symp., edited by A. W. Hahn Columbia, MO: Univ. of Missouri, 1986, vol. 22, p. 35–40.
 48. Holm‐Rutili, L., and T. Berglindh. Pentagastrin and gastric mucosal blood flow. Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G575–G580, 1986.
 49. Hunt, B. F., S. C. Leavitt, and D. C. Hempstead. Digital processing chain for a Doppler ultrasound subsystem. Hewlett‐Packard J. 37: 45–48, 1986.
 50. Hyman, E. S. Linear system for quantitating hydrogen at a platinum electrode. Circ. Res. 9: 1093–1097, 1961.
 51. Jacobson, E. D. Clearances of the gastric mucosa. Gastroenterology 54: 434–448, 1968.
 52. Jacobson, E. D., M. M. Eisenberg, and K. G. Swan. Effects of histamine on gastric blood flow in conscious dogs. Gastroenterology 51: 466–472, 1966.
 53. Jacobson, E. D., R. H. Linford, and M. I. Grossman. Gastric secretion in relation to mucosal blood flow studied by a clearance technic. J. Clin. Invest. 45: 1–13, 1966.
 54. Jodal, M., U. Haglung, and O. Lundgren. Countercurrent exchange mechanisms in the small intestine. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd and D. N. Granger. New York: Raven, 1984, p. 83–98.
 55. Johnson, J. M., W. F. Taylor, A. P. Shepherd, and M. K. Park. Laser‐Doppler measurement of skin blood flow: comparison with plethysmography. J. Appl. Physiol. 56: 798–803, 1984.
 56. Kety, S. S. The theory and application of the exchange of inert gas at the lungs and tissues. Pharmacol. Rev. 3: 1–41, 1951.
 57. Kety, S. S., and C. F. Schmidt. The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am. J. Physiol. 143: 53–66, 1945.
 58. Kiel, J. W., G. L. Riedel, G. R. DiResta, and A. P. Shepherd. Gastric mucosal blood flow measured by laser‐Doppler velocimetry. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G539–G545, 1985.
 59. Kiel, J. W., G. L. Riedel, and A. P. Shepherd. Autoregulation of gastric mucosal blood flow (Abstract). Proc. Int. Congr. Physiol. Sci. 30th, Vancouver, Canada, 1986, vol. 16, p. 123.
 60. Kilpatrick, D., J. V. Tyberg, and W. W. Parmley. Blood velocity measurement by fiber optic laser Doppler anemometry. IEEE Trans. Biom. Eng. 29: 142–145, 1982.
 61. Kobrine, A. I., T. F. Doyle, and A. N. Martins. Spinal cord blood flow in the rhesus monkey by the hydrogen clearance method. Surg. Neurol. 2: 197–200, 1974.
 62. Koshu, K., K. Kamiyama, N. Oka, S. Endo, A. Takaku, and T. Saito. Measurement of regional blood flow using hydrogen gas generated by electrolysis. Stroke 13: 483–487, 1982.
 63. Koshu, K., J. Nakada, Y. Hirashima, S. Endo, A. Takaku, and T. Saito. Measurement of regional cerebral blood flow by an electrolytic method using a monopolar electrode. J. Cereb. Blood Flow Metab. 3: S111–S112, 1983.
 64. Kvietys, P. R., A. P. Shepherd, and D. N. Granger. Laser‐Doppler, H2 clearance, and microsphere estimates of mucosal blood flow. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G221–G227, 1985.
 65. Lassen, N. A., and W. Perl. Tracer Kinetic Methods in Medical Physiology. New York: Raven, 1979.
 66. Le‐Cong, P. Development of a Laser Doppler Velocimeter and Its Applications to Microcirculation Studies. Univ. of California, San Diego, 1976 Dissertation. University Microfilm Order No. 77–522.
 67. Le‐Cong, P., and R. H. Loveberg. Analysis of dual beam laser velocimeter applied to microcirculation studies. Rev. Sci. Instrum. 51: 565–574, 1980.
 68. Le‐Cong, P., and B. W. Zweifach. In vivo and in vitro velocity measurements in microvasculature with a laser. Microvasc. Res. 17: 131–141, 1979.
 69. Lekven, J., and K. S. Anderson. Migration of 15 micron microspheres from infarcted myocardium. Cardiovasc. Res. 14: 280–287, 1980.
 70. Leonard, J. J., R. W. Emery, S. Einzig, D. M. Nicoloff, and I. J. Fox. Evidence for arteriovenous communications in the gastrointestinal tract. Surg. Forum 28: 419–421, 1977.
 71. Leung, F. W., P. H. Guth, O. U. Scremin, E. M. Golanska, and G. L. KauffmanJr. Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit. Gastroenterology 87: 28–36, 1984.
 72. Leung, F. W., J. Washington, G. L. Kauffman, Jr., and P. H. Guth. Endoscopic measurement of gastric corpus mucosal blood flow in conscious dogs. Dig. Dis. Sci. 31: 625–630, 1986.
 73. Lifson, N. Use of microspheres to measure intraorgan distribution of blood flow in the splanchnic circulation. In: Measurement of Blood Flow. Applications to the Splanchnic Circulation, edited by D. N. Granger and G. B. Bulkley. Baltimore, MD: Williams & Wilkins, 1981, p. 177–194.
 74. Lübbers, D. W., R. Wodick, K. Stosseck, and H. Acker. Problems concerning the H2 inhalation technique to determine the cerebral blood flow by means of palladinized Pt electrodes. In: Cerebral Blood Flow: Clinical and Experimental Results, edited by M. Brock, C. Fieschi, D. H. Ingvar, N. A. Lassen, and K. Schürmann. Berlin: Springer‐Verlag, 1969, p. 39–41.
 75. Lundgren, O. Studies on blood flow distribution and counter‐current exchange in the small intestine. Acta Physiol. Scand. 303: 5–42, 1967.
 76. Lundgren, O. Microcirculation of the gastrointestinal tract and pancreas. In: Handbook of Physiology. The Cardiovascular System. Microcirculation, edited by E. M. Renkin and C. C. Michel. Bethesda, MD: Am. Physiol. Soc., 1984, sect. 2, vol. IV, pt. 2, chapt. 13, p. 799–863.
 77. Mackie, D. B., and M. D. Turner. Long‐term blood flow studies in the gastric submucosa of unanesthetized rats. Arch. Surg. 103: 500–503, 1971.
 78. Mackie, D. B., and M. D. Turner. Vagotomy and submucosal blood flow. Arch. Surg. 102: 626–629, 1971.
 79. Madden, R. E., A. Paparo, and M. Schwartz. Limiting vascular diameters in various organs. Arch. Surg. 96: 130–137, 1968.
 80. Magnin, P. A. Doppler effect: history and theory. Hewlett‐Packard J. 37: 26–31, 1986.
 81. Makowski, E. L., G. Meschia, W. Droegemueller, and F. C. Battaglia. Measurement of umbilical arterial blood flow to the sheep placenta and fetus in utero. Circ. Res. 23: 623–631, 1968.
 82. Maxwell, L. C., A. P. Shepherd, and C. A. McMahan. Microsphere passage through intestinal circulation: via shunts or capillaries? Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H217–H224, 1985.
 83. Maxwell, L. C., A. P. Shepherd, and G. L. Riedel. Vasodilation or altered perfusion pressure moves 15‐μm spheres trapped in the gut wall. Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H123–H127, 1982.
 84. Maxwell, L. C., A. P. Shepherd, G. L. Riedel, and M. D. Morris. Effect of microsphere size on apparent intramural distribution of intestinal blood flow. Am. J. Physiol. 241 (Heart Circ. Physiol. 10): H408–H414, 1981.
 85. McMahan, C. A., L. C. Maxwell, and A. P. Shepherd. Estimation of the distribution of blood vessel diameters from the arteriovenous passage of microspheres. Biometrics 42: 371–380, 1986.
 86. Mickflickier, A. B., J. H. Bond, B. Sircar, and M. D. Levitt. Intestinal villus blood flow measured with carbon monoxide and microspheres. Am. J. Physiol. 230: 916–919, 1976.
 87. Miller, T. A., J. M. Henagan, and T. M. Loy. Impairment of aminopyrine clearance in aspirin‐damaged canine gastric mucosa. Gastroenterology 85: 643–649, 1983.
 88. Mishina, H., T. Koyama, and T. Asakura. Velocity measurements of blood flow in the capillary and vein using a laser‐Doppler microscope. Appl. Opt. 14: 2326–2327, 1975.
 89. Misrahy, G. A., and L. C. Clark. Use of the platinum black cathode for local blood flow measurements in vivo (Abstract). Proc. Int. Cong. Physiol. Sci., 22nd, Brussels, vol. 1, 1956, p. 650.
 90. Mito, K. Measurement of arterial blood flow profile by an optical fiber laser Doppler flowmeter. Jpn. J. Med. Electron. Biol. Eng. 19: 383–384, 1981.
 91. Moody, F. G. Gastric blood flow and acid secretion during direct intraarterial histamine administration. Gastroenterology 52: 216–224, 1967.
 92. Moody, F. G. Oxygen consumption during thiocyanate inhibition of gastric acid secretion in dogs. Am. J. Physiol. 215: 127–131, 1968.
 93. Moody, F. G., and R. P. Durbin. Effects of glycine and other instillates on concentration of gastric acid. Am. J. Physiol. 209: 122–126, 1965.
 94. Mørkrid, L., J. Ofstad, and Y. Willassen. Diameter of afferent arterioles during autoregulation estimated from microsphere data in the dog kidney. Circ. Res. 42: 181–191, 1978.
 95. Müller‐Lissner, S. A., A. Sonnenberg, and A. L. Blum. Does gastric aminopyrine clearance reflect gastric mucosal blood flow or parietal cell function. Gut 23: 997–1002, 1981.
 96. Murakami, M., M. Moriga, T. Miyake, and H. Uchino. Contact electrode method in hydrogen gas clearance technique: a new method for determination of regional gastric mucosal blood flow in animals and humans. Gastroenterology 82: 457–467, 1982.
 97. Murakami, M., H. Saida, M. Seki, and T. Miyake. Measurement of gastric mucosal blood flow by laser‐Doppler velocimetry. Nippon Shokakibyo Gakkai Zasshi 80: 2275–2276, 1983.
 98. Nilsson, G. E. Signal processor for laser Doppler tissue flowmeters. Med. Biol. Eng. Comput. 22: 343–348, 1984.
 99. Nilsson, G. E., T. Tenland, and P. A. Öberg. Evaluation of a laser Doppler flowmeter for measurement of tissue blood flow. IEEE Trans. Biomed. Eng. 27: 597–604, 1980.
 100. Ofstad, J., L. Mörkrid, and Y. Willassen. Diameter of afferent arteriole in the dog kidney estimated by the microsphere method. Scand. J. Clin. Lab. Invest. 35: 767–774, 1975.
 101. Ollkkonen, H., P. Simonen, T. Immonen, T. Jaaskelainen, and J. Fraki. Dual diode transducer for laser‐Doppler skin blood velocimeter. J. Biomed. Eng. 6: 75–77, 1984.
 102. Overbeck, H. W. Intestinal circulation during arterial hypertension. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd and D. N. Granger. New York: Raven, 1984, p. 349–360.
 103. Pawlik, W. W., J. D. Fondacaro, and E. D. Jacobson. Metabolic hyperemia in canine gut. Am. J. Physiol. 239 (Gastrointest, Liver Physiol. 2): G12–G17, 1980.
 104. Phibbs, R. H., and L. Dong. Nonuniform distribution of microspheres in blood flowing through a medium sized artery. Can. J. Physiol. Pharmacol. 48: 415–421, 1970.
 105. Prinzmetal, M., B. Simkin, H. C. Bergman, and H. E. Kruger. Studies on the coronary circulation. II. The collateral circulation of the normal human heart by coronary perfusion with radioactive erythrocytes and glass spheres. Am. Heart J. 33: 420–442, 1947.
 106. Riva, C. E., B. Ross, and G. B. Benedek. Laser‐Doppler measurements of blood flow in capillary tubes and retinal arteries. Invest. Ophthalmol. 11: 936–944, 1972.
 107. Rudick, J., J. L. Werther, M. L. Chapman, D. A. Dreiling, and H. D. Janowitz. Mucosal blood flow in canine antral and fundic pouches. Gastroenterology 60: 263–271, 1971.
 108. Rudolph, A. M., and R. A. Heymann. The circulation of the fetus in utero. Circ. Res. 21: 163–184, 1967.
 109. Ruppin, R., and L. Demling. Gastric aminopyrine clearance—an obsolete technique? Hepato‐Gastroenterology 31: 155–157, 1984.
 110. Salerud, G. Laser‐Doppler Tissue Flowmetry. Fiberoptic Methods in Microvascular Research. Linkoping, Sweden: Linkoping Univ., 1986 Dissertation. (Linkoping Studies in Science and Technology Dissertations, No. 137, Linkoping University Medical Dissertations, No. 216.).
 111. Sarelius, I. H., L. C. Maxwell, S. D. Gray, and B. R. Duling. Capillarity and fiber types in the cremaster muscle of rat and hamster. Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H368–H374, 1983.
 112. Semb, B. K. H. Gastric flow measured with hydrogen clearance technique. Scand. J. Gastroenterol. 14: 641–646, 1979.
 113. Semb, B. K. H. Changes of regional gastric flow measured by hydrogen clearance technique after histamine stimulation in conscious animals. Scand. J. Gastroenterol. 16: 795–800, 1981.
 114. Semb, B. K. H. The effect of catecholamines on gastric mucosal flow. Scand. J. Gastroenterol. 17: 663–670, 1982.
 115. Semb, B. K. H. Regional gastric flow changes after meal stimulation measured by the hydrogen clearance technique in conscious cats. Scand. J. Gastroenterol. 17: 839–842, 1982.
 116. Shepherd, A. P. Intestinal blood flow autoregulation during foodstuff absorption. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H156–H162, 1980.
 117. Shepherd, A. P., G. R. DiResta, J. W. Kiel, and G. L. Riedel. Hybrid blood flow‐probe for simultaneous H2 clearance and laser‐Doppler velocimetry (Abstract). Proc. Int. Congr. Physiol. Sci. 30th, Vancouver, Canada, 1986, vol. 16, p. 123.
 118. Shepherd, A. P., L. C. Maxwell, and E. D. Jacobson. Limitations of the microsphere technique to fractionate intestinal blood flow. In: Measurement of Blood Flow. Applications to the Splanchnic Circulation, by D. N. Granger and G. B. Bulkley. Baltimore, MD: Williams & Wilkins, 1981, p. 195–200.
 119. Shepherd, A. P., L. C. Maxwell, and G. L. Riedel. Microsphere fractionation of intestinal blood flow. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G644–G645, 1984.
 120. Shepherd, A. P., and G. L. Riedel. Continuous measurement of intestinal mucosal blood flow by laser‐Doppler velocimetry. Am. J. Physiol. 242 (Gastrointest. Liver Physiol. 5): G668–G672, 1982.
 121. Shepherd, A. P., and G. L. Riedel. Effect of pulsatile pressure and metabolic rate on intestinal autoregulation. Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H769–H775, 1982.
 122. Shepherd, A. P., and G. L. Riedel. Differences in reactive hyperemia between the intestinal mucosa and muscularis. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G617–G622, 1984.
 123. Shepherd, A. P., and G. L. Riedel. Laser‐Doppler blood flowmetry of intestinal mucosal hyperemia induced by glucose and bile. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G393–G397, 1985.
 124. Shepherd, A. P., G. L. Riedel, L. C. Maxwell, and J. W. Kiel. Selective vasodilators redistribute intestinal blood flow and depress oxygen uptake. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G377–G384, 1984.
 125. Shepherd, A. P., G. L. Riedel, and W. F. Ward. Laser‐Doppler measurements of blood flow within the intestinal wall and on the surface of the liver. In: Microcirculation of the Alimentary Tract‐Physiology and Pathology, edited by A. Koo, S. K. Lam, and L. H. Smaje. Singapore: World Scientific, 1983, p. 115–129.
 126. Shima, I., S. Yamauchi, T. Matsumoto, M. Kunishita, K. Shinoda, N. Yoshimizu, S. Nomura, and M. Yoshimura. A new method for monitoring circulation of grafted bone by use of electrochemically generated hydrogen. Clin. Orthop. Relat. Res. 198: 244–249, 1985.
 127. Shore, P. A., B. B. Brodie, and C. A. M. Hogben. The gastric secretion of drugs: a pH partition hypothesis. J. Pharmacol. Exp. Ther. 119: 361–369, 1957.
 128. Smits, G. J., R. J. Roman, and J. H. Lombard. Evaluation of laser‐Doppler flowmetry as a measure of tissue blood flow. J. Appl. Physiol. 61: 666–672, 1986.
 129. Sonnenberg, A., and A. L. Blum. Limitations to measurement of gastric mucosal blood flow by [14C]aminopyrine clearance. In: Gastrointestinal Mucosal Blood Flow, edited by L. P. Fielding New York: Churchill Livingstone, 1980, p. 43–58.
 130. Sonnenberg, A., T. Berglindh, M. J. M. Lewin, J. A. Fischer, G. Sachs, and A. L. Blum. Stimulation of acid secretion in isolated gastric cells. In: Hormone Receptors in Digestion and Nutrition, edited by G. Rosselin, P. Fromageot, and S. Bonfils. Amsterdam: Elsevier/North‐Holland, 1979, p. 337–348.
 131. Stern, M. D. In vivo evaluation of microcirculation by coherent light scattering. Nature Lond. 254: 56–58, 1975.
 132. Stern, M. D., P. D. Bowen, R. Parma, R. W. Osgood, R. L. Bowman, and J. H. Stein. Measurement of renal cortical and medullary blood flow by laser‐Doppler spectroscopy in the rat. Am. J. Physiol. 236 (Renal Fluid Electrolyte Physiol. 5): F80–F87, 1979.
 133. Stern, M. D., D. L. Lappe, P. D. Bowen, J. E. Chimosky, G. A. Holloway, Jr., H. R. Keiser, and R. L. Bowman. Continuous measurement of tissue blood flow by laser‐Doppler spectroscopy. Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H441–H448, 1977.
 134. Stosseck, K. Hydrogen exchange through the pial vessel wall and its meaning for the determination of local cerebral blood flow. Pfluegers Arch. 320: 111–119, 1970.
 135. Stosseck, K., and D. W. Lübbers. Determination of micro‐flow of the cerebral cortex by means of electrochemically generated hydrogen. In: Brain and Blood Flow, edited by R. W. R. Russell London: Pitman, 1970, p. 80–84.
 136. Stosseck, K., D. W. Lübbers, and N. Cottin. Determination of local blood flow (microflow) by electrochemically generated hydrogen: Construction and application of the measuring probe. Pfluegers Arch. 348: 225–238, 1974.
 137. Swan, K. G., and E. D. Jacobson. Gastric blood flow and secretion in conscious dogs. Am. J. Physiol. 212: 891–896, 1967.
 138. Tague, L. L., and E. D. Jacobson. Evaluation of [14C]‐aminopyrine clearance for determination of gastric mucosal blood flow. Proc. Soc. Exp. Biol. Med. 151: 707–710, 1976.
 139. Takeshita, H., Y. Kotani, and S. Okabe. Comparative study of hydrogen and aminopyrine clearance methods for determination of gastric mucosal blood flow in dogs. Dig. Dis. Sci. 29: 841–847, 1984.
 140. Tanaka, T., and G. B. Benedek. Measurement of velocity of blood flow (in vivo) using a fiber optic catheter and optical mixing spectroscopy. Appl. Opt. 14: 189–200, 1975.
 141. Tanaka, T., C. Riva, and I. Ben‐Sira. Blood velocity measurements in human retinal vessels. Science Wash. DC 186: 830–831, 1974.
 142. Utley, J., E. L. Carlson, J. I. E. Hoffman, H. M. Martinez, and G. D. Buckberg. Total and regional myocardial blood flow measurements with 25μ, 15μ, 9μ, and filtered 1–10μ diameter microspheres and antipyrine in dogs and sheep. Circ. Res. 34: 391–405, 1974.
 143. Varhaug, J.‐E., K. Svanes, C. Svanes, and J. Lekven. Gastric blood flow determination: intramural distribution and arteriovenous shunting of microspheres. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G468–G479, 1984.
 144. Watkins, D. W., and G. A. Holloway. An instrument to measure cutaneous blood flow using the Doppler shift of laser light. IEEE Trans. Biomed. Eng. 25: 28–33, 1978.
 145. White, D. N. Johann Christian Doppler and his effect—a brief history. Ultrasound Med. Biol. 8: 583–591, 1982.
 146. Wunderlich, R. W., R. L. Folger, D. B. Giddon, and B. R. Ware. Laser‐Doppler blood flow meter and optical plethysmograph. Rev. Sci. Instrum. 51: 1258–1262, 1980.
 147. Yeh, Y., and H. Z. Cummings. Localized fluid flow measurements with an He‐Ne laser spectrometer. Appl. Phys. Lett. 4: 176–178, 1964.
 148. Young, W. H2 clearance measurement of blood flow: a review of technique and polarographic principles. Stroke 11: 552–564, 1980.
 149. Yu, Y. M., L. C. Yu, and C. C. Chou. Distribution of blood flow in the intestine with hypertonic glucose in the lumen. Surgery St. Louis 78: 520–525, 1975.

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A. P. Shepherd, J. W. Kiel. Gastrointestinal blood flow‐measuring techniques. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 1335-1370. First published in print 1989. doi: 10.1002/cphy.cp060137