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Peripheral Inert‐Gas Exchange

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Abstract

The sections in this article are:

1 Basic Principles of Peripheral Tissue Exchange
1.1 Inclusion of Pulmonary Gas Exchange in Tissue Inert‐Gas Uptake and Elimination
1.2 Comparison of Multicompartment Models With Actual Data
2 Consideration of Tissue‐Blood Diffusion of Inert Gases
2.1 Diffusional Shunts
2.2 Intertissue Diffusion
2.3 Evaluation of Assumptions
3 Application of Inert Gases to Measurement of Organ Perfusion
3.1 Technique 1: Average Organ Blood Flow by Measurement of Prolonged Inert‐Gas Uptake
3.2 Technique 2: Blood Flow by Arterial Bolus Injection and Subsequent Tissue Washout Analysis
3.3 Technique 3: Blood Flow by Arterial Bolus Injection and Measurement of Height‐Area Ratio of Concentration‐Time Curve
3.4 Technique 4: Local Injection of Tracer and Measurement of Blood Flow by Monitoring Subsequent Removal
3.5 Evaluation of Methods for Measuring Tissue Perfusion With Inert Gases
4 Summary
Figure 1. Figure 1.

Important variables in peripheral tissue gas exchange. In this simplest model, tissue tension (Pti) of a gas is uniform both in radial and in axial directions at any point in time. Tissue is characterized by its volume (Vti), blood flow (Q), and solubility (α) for the gas. For blood solubility β, ability of blood to transport gas is βQ. Storage capability of tissue for gas is αVti. Washin or washout of gas in such tissue is exponential, and exponent is Q/(λtiVti), where λti is ratio of α to β and is known as tissue‐blood partition coefficient of gas. Pa, inflowing arterial tension of gas; Pv, outflowing venous tension of gas.

Figure 2. Figure 2.

Calculated concentration‐time profiles for uptake (left graph) and elimination (right graph) of 7 gases in mixed venous blood. During 60 min of uptake, arterial concentration is constant and mixed venous values are given as percentage of that level. Gases are 1) N2, 2) N2O, 3) cyclopropane, 4) fluroxene, 5) enflurane, 6) halothane, and 7) diethyl ether. Note how similar both uptake and elimination curves are for all gases, despite differences in their partition coefficients (Table 2) when arterial levels are held constant.

Figure 3. Figure 3.

Gas tension‐time profiles for uptake (left graphs) and elimination (right graphs) of N2 (A) and N2O (B) in mixed venous blood under conditions identical to those of Fig. 2 (solid lines). Dotted lines for each gas indicate gas tensions in each of 4 standard tissues as labeled. Vessel‐rich tissues equilibrate with inflowing arterial blood in ∼10 min (N2), whereas muscle, vessel‐poor, and fat tissues fail to reach arterial levels within 1 h of uptake (or elimination). Rate of equilibration is determined by conductance‐capacitance ratio of gas in each tissue.

Figure 4. Figure 4.

Organizational arrangement of lungs, circulation, and several tissues, demonstrating their interdependence. For determining gas tensions in lungs, blood, and tissues, 1) the key pulmonary variables are inspired gas tension, alveolar gas tension and volume, pulmonary tissue volume, alveolar ventilation, cardiac output, and blood‐gas partition coefficient and 2) the key tissue variables are tissue gas tension, tissue volume and blood flow, and tissue‐blood partition coefficient.

Figure 5. Figure 5.

Gas tension‐time profiles for uptake (left graphs) and elimination (right graphs) of 7 gases of Fig. 2 computed during 60 min of uptake at constant inspired tension and during 60 min of elimination (0 inspired tension). Tissue variables are as in Fig. 2; however, this figure allows for pulmonary gas exchange and recirculation from tissues to lungs according to model of Fig. 4. Time‐course calculations are shown for both arterial (A) and mixed venous (B) gas tensions. Rate of equilibration is inversely related to blood‐gas partition coefficient, with large differences among gases. In all cases, true equilibrium would be reached when tensions were 100% (uptake) or 0% (elimination) of inspired.

Figure 6. Figure 6.

Comparison of measured and predicted end‐tidal N2O concentrations during uptake (left) and elimination (right). Predictions come from model of Fig. 4 and Eqs. 30–35 in text. Excellent agreement is noted during both phases, indicating that 4 basic tissue compartments and simple convective mass‐balance principles are sufficient to explain actual data.

Measured data from Rackow et al. 70 and Salanitre et al. 72
Figure 7. Figure 7.

Comparison of real arterial and mixed venous cyclopropane concentrations with those predicted from numerical analysis described in text (prediction based on considering 4 tissue compartments and homogeneous lung). From 2 studies 70,75, it is evident that arterial data (•, ○) are quite well followed by simple model. However, there is unexplained difference between actual and predicted mixed venous levels (▪). Tables 3 and 4 give additional comparisons with better agreement between measured and predicted mixed venous levels.

Figure 8. Figure 8.

Comparison of measured and predicted arterial halothane concentrations during uptake. Again, Eqs. 30–35 were used for predictions. Figure emphasizes that standard variable values from Table 2 and 4‐compartment model satisfactorily account for observed arterial values.

Data from Sechzer et al. 77
Figure 9. Figure 9.

Two possible models to explain “diffusional shunts” in tissue. A: there is direct diffusion between inflowing arteriole and outflowing venule. B: arterioles and venules within tissue may be arranged spatially so that they are conducive to significant diffusion between arterioles and venules.

From Roth and Feigl 71
Figure 10. Figure 10.

Nitrous oxide uptake method of Kety and Schmidt 42 applied to kidneys for measuring organ blood flow. The N2O levels are recorded over several minutes in both arterial and venous blood of organ until they are equal. Blood flow per unit tissue volume is then given by product of tissue‐blood partition coefficient and equilibrium concentration of N2O divided by area between arterial and venous curves. A: normal renal flow, 290 ml.100 g−1.min−1. B: slow renal flow, 122 ml.100 g−1.min−1.

From Conn et al. 15
Figure 11. Figure 11.

The 133Xe washout technique for measuring calf muscle blood flow. Small volume (0.1 ml) of 133Xe dissolved in saline is injected directly into muscle, and its subsequent washout is monitored externally by scintillation detector after 2‐min period of ischemic exercise. In normal case washout is rapid, and difference between normal curve and data from patient with occlusive arterial disease is striking. The 133Xe counts on ordinate are on log scale, and blood flow is calculated from log slope of washout curve.

From Lassen and Larsen 51
Figure 12. Figure 12.

Comparison of muscle blood flow (q) measured by 133Xe washout (see Fig. 11) and that measured by radioactive microspheres injected into muscle's arterial supply. Latter measurements correlate well with direct volumetric measurements of venous outflow. Figure shows 1) correlation between 2 methods; 2) much scatter, indicating that individual measurements may be considerably in error; and 3) underestimation of blood flow by about a factor of 2 when 133Xe method is used. Open symbols, muscle stimulated; closed symbols, muscle resting; circles, gastrocnemius; squares, vastus lateralis; triangles, triceps.

From Cerretelli et al. 10


Figure 1.

Important variables in peripheral tissue gas exchange. In this simplest model, tissue tension (Pti) of a gas is uniform both in radial and in axial directions at any point in time. Tissue is characterized by its volume (Vti), blood flow (Q), and solubility (α) for the gas. For blood solubility β, ability of blood to transport gas is βQ. Storage capability of tissue for gas is αVti. Washin or washout of gas in such tissue is exponential, and exponent is Q/(λtiVti), where λti is ratio of α to β and is known as tissue‐blood partition coefficient of gas. Pa, inflowing arterial tension of gas; Pv, outflowing venous tension of gas.



Figure 2.

Calculated concentration‐time profiles for uptake (left graph) and elimination (right graph) of 7 gases in mixed venous blood. During 60 min of uptake, arterial concentration is constant and mixed venous values are given as percentage of that level. Gases are 1) N2, 2) N2O, 3) cyclopropane, 4) fluroxene, 5) enflurane, 6) halothane, and 7) diethyl ether. Note how similar both uptake and elimination curves are for all gases, despite differences in their partition coefficients (Table 2) when arterial levels are held constant.



Figure 3.

Gas tension‐time profiles for uptake (left graphs) and elimination (right graphs) of N2 (A) and N2O (B) in mixed venous blood under conditions identical to those of Fig. 2 (solid lines). Dotted lines for each gas indicate gas tensions in each of 4 standard tissues as labeled. Vessel‐rich tissues equilibrate with inflowing arterial blood in ∼10 min (N2), whereas muscle, vessel‐poor, and fat tissues fail to reach arterial levels within 1 h of uptake (or elimination). Rate of equilibration is determined by conductance‐capacitance ratio of gas in each tissue.



Figure 4.

Organizational arrangement of lungs, circulation, and several tissues, demonstrating their interdependence. For determining gas tensions in lungs, blood, and tissues, 1) the key pulmonary variables are inspired gas tension, alveolar gas tension and volume, pulmonary tissue volume, alveolar ventilation, cardiac output, and blood‐gas partition coefficient and 2) the key tissue variables are tissue gas tension, tissue volume and blood flow, and tissue‐blood partition coefficient.



Figure 5.

Gas tension‐time profiles for uptake (left graphs) and elimination (right graphs) of 7 gases of Fig. 2 computed during 60 min of uptake at constant inspired tension and during 60 min of elimination (0 inspired tension). Tissue variables are as in Fig. 2; however, this figure allows for pulmonary gas exchange and recirculation from tissues to lungs according to model of Fig. 4. Time‐course calculations are shown for both arterial (A) and mixed venous (B) gas tensions. Rate of equilibration is inversely related to blood‐gas partition coefficient, with large differences among gases. In all cases, true equilibrium would be reached when tensions were 100% (uptake) or 0% (elimination) of inspired.



Figure 6.

Comparison of measured and predicted end‐tidal N2O concentrations during uptake (left) and elimination (right). Predictions come from model of Fig. 4 and Eqs. 30–35 in text. Excellent agreement is noted during both phases, indicating that 4 basic tissue compartments and simple convective mass‐balance principles are sufficient to explain actual data.

Measured data from Rackow et al. 70 and Salanitre et al. 72


Figure 7.

Comparison of real arterial and mixed venous cyclopropane concentrations with those predicted from numerical analysis described in text (prediction based on considering 4 tissue compartments and homogeneous lung). From 2 studies 70,75, it is evident that arterial data (•, ○) are quite well followed by simple model. However, there is unexplained difference between actual and predicted mixed venous levels (▪). Tables 3 and 4 give additional comparisons with better agreement between measured and predicted mixed venous levels.



Figure 8.

Comparison of measured and predicted arterial halothane concentrations during uptake. Again, Eqs. 30–35 were used for predictions. Figure emphasizes that standard variable values from Table 2 and 4‐compartment model satisfactorily account for observed arterial values.

Data from Sechzer et al. 77


Figure 9.

Two possible models to explain “diffusional shunts” in tissue. A: there is direct diffusion between inflowing arteriole and outflowing venule. B: arterioles and venules within tissue may be arranged spatially so that they are conducive to significant diffusion between arterioles and venules.

From Roth and Feigl 71


Figure 10.

Nitrous oxide uptake method of Kety and Schmidt 42 applied to kidneys for measuring organ blood flow. The N2O levels are recorded over several minutes in both arterial and venous blood of organ until they are equal. Blood flow per unit tissue volume is then given by product of tissue‐blood partition coefficient and equilibrium concentration of N2O divided by area between arterial and venous curves. A: normal renal flow, 290 ml.100 g−1.min−1. B: slow renal flow, 122 ml.100 g−1.min−1.

From Conn et al. 15


Figure 11.

The 133Xe washout technique for measuring calf muscle blood flow. Small volume (0.1 ml) of 133Xe dissolved in saline is injected directly into muscle, and its subsequent washout is monitored externally by scintillation detector after 2‐min period of ischemic exercise. In normal case washout is rapid, and difference between normal curve and data from patient with occlusive arterial disease is striking. The 133Xe counts on ordinate are on log scale, and blood flow is calculated from log slope of washout curve.

From Lassen and Larsen 51


Figure 12.

Comparison of muscle blood flow (q) measured by 133Xe washout (see Fig. 11) and that measured by radioactive microspheres injected into muscle's arterial supply. Latter measurements correlate well with direct volumetric measurements of venous outflow. Figure shows 1) correlation between 2 methods; 2) much scatter, indicating that individual measurements may be considerably in error; and 3) underestimation of blood flow by about a factor of 2 when 133Xe method is used. Open symbols, muscle stimulated; closed symbols, muscle resting; circles, gastrocnemius; squares, vastus lateralis; triangles, triceps.

From Cerretelli et al. 10
References
 1. Allott, P. R., A. Steward, and W. W. Mapleson. Pharmacokinetics of halothane in the dog. Br. J. Anaesth. 48: 279–295, 1976.
 2. Andersen, A. M., and J. Ladefoged. Partition coefficient of 133‐xenon between various tissues and blood in vivo. Scand. J. Clin. Lab. Invest. 19: 72–78, 1967.
 3. Ashman, M. N., W. B. Blesser, and R. B. Epstein. A nonlinear model for the uptake and distribution of halothane in man. Anesthesiology 33: 419–429, 1970.
 4. Aukland, K., S. Akre, and S. Leraand. Arteriovenous countercurrent exchange of hydrogen gas in skeletal muscle. Scand. J. Clin. Lab. Invest. Suppl. 99: 72–75, 1967.
 5. Aust, R., L. Backlund, B. Drettner, B. Falck, and B. Jung. Comparative measurements of the mucosal blood flow in the human maxillary sinus by plethysmography and by xenon. Acta Oto‐Laryngol. 85: 111–115, 1978.
 6. Bassingthwaighte, J. B., and T. Yipintsoi. The emergence function: effects of flow and capillary‐tissue exchange in the heart. In: Capillary Permeability, edited by C. Crone and N. A. Lassen. Copenhagen: Munksgaard, 1970, p. 580–585. (Alfred Benzon Symp. 2.)
 7. Beneken Kolmer, H. H., A. G. Burm, C. A. Cramers, J. M. Ramakers, and H. L. Vader. The uptake and elimination of halothane in dogs: a two‐ or multicompartment system? II: Evaluation of wash‐in and wash‐out curves. Br. J. Anaesth. 47: 1169–1175, 1975.
 8. Brodersen, P., P. Sejrsen, and N. A. Lassen. Diffusion bypass of xenon in brain circulation. Circ. Res. 32: 363–369, 1973.
 9. Cander, L. Solubility of inert gases in human lung tissue. J. Appl. Physiol. 14: 538–540, 1959.
 10. Cerretelli, P., C. Marconi, D. Pendergast, M. Meyer, N. Heisler, and J. Piiper. Blood flow in exercising muscles by xenon clearance and by microsphere trapping. J. Appl. Physiol. 56: 24–30, 1984.
 11. Chimoskey, J. E. Skin blood flow by 133Xe disappearance validated by venous occlusion plethysmography. J. Appl. Physiol. 32: 432–435, 1972.
 12. Christensen, N. J. The significance of work load and injected volumes in xenon133 measurement of muscular blood flow. Acta Med. Scand. 183: 445–447, 1968.
 13. Cohen, E. N., K. L. Chow, and L. Mathers. Autoradiographic distribution of volatile anesthetics within the brain. Anesthesiology 37: 324–331, 1972.
 14. Conn, H. L., Jr. Equilibrium distribution of radioxenon in tissue: xenon‐hemoglobin association curve. J. Appl. Physiol. 16: 1065–1070, 1961.
 15. Conn, H. L., Jr., W. Anderson, and S. Arena. Gas diffusion technique for measurement of renal blood flow with special reference to the intact, anuric subject. J. Appl. Physiol. 5: 683–689, 1953.
 16. Copperman, R. The theory of inert gas exchange at the lung and tissues. [Cited in Kety (41), p. 9.]
 17. Cowles, A. L., H. H. Borgstedt, and A. J. Gillies. An electric analog for the uptake, distribution and excretion of inhalation anesthetics. Data Acquis. Process. Biol. Med. 5: 75–92, 1968.
 18. Cowles, A. L., H. H. Borgstedt, and A. J. Gillies. Tissue weights and rates of blood flow in man for the prediction of anesthetic uptake and distribution. Anesthesiology 35: 523–526, 1971.
 19. Cowles, A. L., H. H. Borgstedt, and A. J. Gillies. The uptake and distribution of four inhalation anesthetics in dogs. Anesthesiology 36: 558–570, 1972.
 20. Crane, R., M. Yates, and S. N. Steen. An improved electronic simulator for the study of the distribution of anaesthetic agents. Br. J. Anaesth. 40: 936–942, 1968.
 21. Cullen, B. F., and E. I. Eger II. Diffusion of nitrous oxide, cyclopropane, and halothane through human skin and amniotic membrane. Anesthesiology 36: 168–173, 1972.
 22. Davies, W. T. Blood flow measurement in patients with intermittent claudication. Angiology 31: 164–175, 1982.
 23. Davis, N. R., and W. W. Mapleson. Structure and quantification of a physiological model of the distribution of injected agents and inhaled anaesthetics. Br. J. Anaesth. 53: 399–405, 1981.
 24. Eger, E. I., II. A mathematical model of uptake and distribution. In: Uptake and Distribution of Anesthetic Agents, edited by E. M. Papper and R. J. Kitz. New York: McGraw‐Hill, 1963, chapt. 7, p. 72–87.
 25. Eger, E. I. II. Intertissue diffusion of anesthetics (Letter to the editor). Anesthesiology 38: 201, 1973.
 26. Eger, E. I., II. Diffusion may limit or may increase anesthetic uptake. In: Anesthetic Uptake and Action, edited by E. I. Eger II. Baltimore, MD: Williams & Wilkins, 1974, chapt. 15, p. 249–257.
 27. Forster, R. E., II. Diffusion factors in gases and liquids. In: Uptake and Distribution of Anesthetic Agents, edited by E. M. Papper and R. J. Kitz. New York: McGraw‐Hill, 1963, chapt. 2, p. 20–29.
 28. Fraser, I. S., B. W. Brown, P. E. Mattner, and B. F. Hutton. Measurements of endometrial blood flow in anaesthetized ewes by xenon133 clearance and microsphere techniques. Q. J. Exp. Physiol. Cogn. Med. Sci. 67: 531–535, 1982.
 29. Goresky, C. A., W. H. Ziegler, and G. G. Bach. Capillary exchange modeling. Barrier‐limited and flow‐limited distribution. Circ. Res. 27: 739–764, 1970.
 30. Haggard, A. W. The absorption, distribution and elimination of ethyl ether. II. Analysis of the mechanism of absorption and elimination of such a gas or vapor as ethyl ether. J. Biol. Chem. 59: 753–770, 1924.
 31. Hennessy, T. R. Inert gas diffusion in heterogeneous tissue I: without perfusion. Bull. Math. Biophys. 33: 235–248, 1971.
 32. Hennessy, T. R. Inert gas diffusion in heterogeneous tissue II: with perfusion. Bull. Math. Biophys. 33: 249–257, 1971.
 33. Hills, B. A. Diffusion versus blood perfusion in limiting the rate of uptake of inert non‐polar gases by skeletal rabbit muscle. Clin. Sci. Lond. 33: 67–87, 1967.
 34. Hirzel, H. O., and H. P. Krayenbuehl. Validity of the 133xenon method for measuring coronary blood flow. Pfluegers Arch. 349: 159–169, 1974.
 35. Hoffmann, D. C. An assessment of the xenon‐133 method of measuring muscle blood flow. Aust. NZ J. Surg. 38: 66–70, 1968.
 36. Hulten, L., M. Jodal, J. Lindhagen, and O. Lundgren. Colonic blood flow in cat and man as analyzed by an inert gas washout technique. Gastroenterology 70: 36–44, 1976.
 37. Jones, H. B. Respiratory system: nitrogen elimination. In: New Medical Physics, edited by O. Glasser. Chicago, IL: Year Book, 1950, vol. 2, p. 855–871.
 38. Kawashiro, T., A. C. Carles, S. F. Perry, and J. Piiper. Diffusivity of various inert gases in rat skeletal muscle. Pfluegers Arch. 359: 219–230, 1975.
 39. Kety, S. S. Measurement of regional circulation by the local clearance of radioactive sodium. Am. Heart J. 38: 321–328, 1949.
 40. Kety, S. S. Quantitative determination of cerebral blood flow in man. In: Methods in Medical Research, edited by V. R. Potter. Chicago, IL: Year Book, 1949, vol. 1, p. 204–217.
 41. Kety, S. S. The theory and applications of the exchange of inert gas at the lungs and tissues. Pharmacol. Rev. 3: 1–41, 1951.
 42. Kety, S. S., and C. F. Schmidt. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values. J. Clin. Invest. 27: 476–484, 1948.
 43. Kirk, W. P., P. W. Parish, and D. A. Morken. In vivo solubility of 85Kr in guinea pig tissues. Health Phys. 28: 249–261, 1975.
 44. Kjellmer, I., I. Lindbjerg, I. Prerovsky, and H. Tonnesen. The relation between blood flow in an isolated muscle measured with the Xe133 clearance and a direct recording technique. Acta Physiol. Scand. 69: 69–78, 1967.
 45. Klocke, F. J., R. C. Koberstein, D. E. Pittman, I. L. Bunnell, D. G. Greene, and D. R. Rosing. Effects of heterogeneous myocardial perfusion on coronary venous H2 desaturation curves and calculations of coronary flow. J. Clin. Invest. 47: 2711–2724, 1968.
 46. Landahl, H. D. On mathematical models of distribution: In: Uptake and Distribution of Anesthetic Agents, edited by E. M. Papper and R. J. Kitz. New York: McGraw‐Hill, 1963, chapt. 16, p. 191–214.
 47. Larson, C. P., Jr. Solubility and partition coefficients. In: Uptake and Distribution of Anesthetic Agents, edited by E. M. Papper and R. J. Kitz. New York: McGraw‐Hill, 1963, chapt. 1, p. 5–19.
 48. Larson, C. P., Jr., E. I. Eger II, and J. W. Severinghaus. Solubility of halothane in blood and tissue homogenates. Anesthesiology 23: 349–355, 1962.
 49. Larson, C. P., Jr., E. I. Eger II, and J. W. Severinghaus. Ostwald solubility coefficient for anesthetic gases in various fluids and tissues. Anesthesiology 23: 686–689, 1962.
 50. Lassen, N. A. Muscle blood flow in normal man and in patients with intermittent claudication evaluated by simultaneous Xe133 and Na24 clearances. J. Clin. Invest. 43: 1805–1812, 1964.
 51. Lassen, N. A., and O. A. Larsen. Measurement of blood flow with freely diffusible indicators as inert gases, antipyrine, labelled water and rubidium. Acta Endocrinol. Suppl. 158: 95–111, 1972.
 52. Lassen, N. A., J. Lindbjerg, and O. Munck. Measurement of blood‐flow through skeletal muscle by intramuscular injection of xenon133. Lancet 1: 686–689, 1964.
 53. Levitt, M. D., and D. G. Levitt. Use of inert gases to study the interaction of blood flow and diffusion during passive absorption from the gastrointestinal tract of the rat. J. Clin. Invest. 52: 1852–1862, 1973.
 54. Lowe, H. J., and K. Hagler. Determination of volatile organic anesthetics in blood, gases, tissues, and lipids: partition coefficients. In: Gas Chromatography in Biology and Medicine, edited by R. Porter. London: Churchill, 1969, p. 86–112. (Ciba Symp.)
 55. Mallett, B. L., and N. Veall. Investigation of cerebral blood‐flow in hypertension, using radioactive xenon inhalation and extracranial recording. Lancet 1: 1081–1082, 1963.
 56. Mapleson, W. W. An electric analogue for uptake and exchange of inert gases and other agents. J. Appl. Physiol. 18: 197–204, 1963.
 57. Mapleson, W. W. Circulation‐time models of the uptake of inhaled anaesthetics and data for quantifying them. Br. J. Anaesth. 45: 319–333, 1973.
 58. Marcus, M. L., C. J. Bischof, and D. D. Heistad. Comparison of microsphere and xenon‐133 clearance method in measuring skeletal muscle and cerebral blood flow. Circ. Res. 48: 748–761, 1981.
 59. Meier, P., and K. I. Zierler. On the theory of the indicator‐dilution method for measurement of blood flow and volume. J. Appl. Physiol. 6: 731–744, 1954.
 60. Meyer, M., U. Tebbe, and J. Piiper. Solubility of inert gases in dog blood and skeletal muscle. Pfluegers Arch. 384: 131–134, 1980.
 61. Ohta, Y., A. Ar, and L. E. Farhi. Solubility and partition coefficients for gases in rabbit brain and blood. J. Appl. Physiol. 46: 1169–1170, 1979.
 62. Ohta, Y., and L. E. Farhi. Cerebral gas exchange: perfusion and diffusion limitations. J. Appl. Physiol. 46: 1164–1168, 1979.
 63. Ohta, Y., S. H. Song, A. C. Groom, and L. E. Farhi. Is inert gas washout from the tissues limited by diffusion? J. Appl. Physiol. 45: 903–907, 1978.
 64. Olszowka, A. J., and P. D. Wagner. Numerical analysis in gas exchange. In: Pulmonary Gas Exchange, edited by J. B. West. New York: Academic, 1980, vol. 1, chapt. 8, p. 263–306.
 65. Onchi, Y., and Y. Asao. Absorption, distribution and elimination of diethyl ether in man. Br. J. Anaesth. 33: 544–548, 1961.
 66. Perl, W., G. T. Lesser, and J. M. Steele. The kinetics of distribution of the fat‐soluble inert gas cyclopropane in the body. Biophys. J. 1: 111–135, 1960.
 67. Perl, W., H. Rackon, E. Salanitre, G. L. Wolf, and R. M. Epstein. Intertissue diffusion effect for inert fat‐soluble gases. J. Appl. Physiol. 20: 621–627, 1965.
 68. Piiper, J., M. Meyer, and P. Scheid. Dual role of diffusion in tissue gas exchange: blood‐tissue equilibration and diffusion shunt. Respir. Physiol. 56: 131–144, 1984.
 69. Power, G. G. Solubility of O2 and CO in blood and pulmonary and placental tissue. J. Appl. Physiol. 24: 468–474, 1968.
 70. Rackow, H., E. Salanitre, R. M. Epstein, G. L. Wolf, and W. Perl. Simultaneous uptake of N2O and cyclopropane in man as a test of compartment model. J. Appl. Physiol. 20: 611–620, 1965.
 71. Roth, A. C., and E. O. Feigl. Diffusional shunting in the canine myocardium. Circ. Res. 48: 470–480, 1981.
 72. Salanitre, E., H. Rackow, L. T. Greene, D. Klonymus, and R. M. Epstein. Uptake and excretion of subanesthetic concentrations of nitrous oxide in man. Anesthesiology 23: 814–822, 1962.
 73. Scheid, F. Schaum's Outline of Theory and Problems of Numerical Analysis. New York: McGraw‐Hill, 1968. (Schaum's Outline Ser.)
 74. Scheid, P., M. Meyer, and J. Piiper. Elements for modeling inert gas washout from heterogeneous tissues. In: Proc. ISOTT Meetings, Ruston, Louisiana, 1983, p. 1–8.
 75. Sechzer, P. H., R. D. Dripps, and H. L. Price. Uptake of cyclopropane by the human body. J. Appl. Physiol. 14: 887–890, 1959.
 76. Sechzer, P. H., H. W. Linde, and R. D. Dripps. Uptake of halothane by the human body (Abstract). Anesthesiology 23: 161, 1962.
 77. Sechzer, P. H., H. W. Linde, R. D. Dripps, and H. L. Price. Uptake of halothane by the human body. Anesthesiology 24: 779–783, 1963.
 78. Sejrsen, P. Blood flow in cutaneous tissue in man studied by washout of radioactive xenon. Circ. Res. 25: 215–229, 1969.
 79. Sejrsen, P., and K. H. Tonnesen. Inert gas diffusion method for measurement of blood flow using saturation techniques. Circ. Res. 22: 679–693, 1968.
 80. Sejrsen, P., and K. H. Tonnesen. Shunting by diffusion of inert gas in skeletal muscle. Acta Physiol. Scand. 86: 82–91, 1972.
 81. Severinghaus, J. W. The rate of uptake of nitrous oxide in man. J. Clin. Invest. 33: 1183–1189, 1954.
 82. Smith, N. T., A. Zwart, and J. E. W. Beneken. Interaction between the circulatory effects and the uptake and distribution of halothane: use of a multiple model. Anesthesiology 37: 47–58, 1972.
 83. Smith, R. E., and M. F. Morales. On the theory of bloodtissue exchanges. I. Fundamental equations. Bull. Math. Biophys. 6: 125–131, 1944.
 84. Sparks, H. V., and D. E. Mohrman. Heterogeneity of flow as an explanation of the multiexponential washout of inert gas from skeletal muscle. Microvasc. Res. 13: 181–184, 1977.
 85. Stosseck, K. Hydrogen exchange through the pial vessel wall and its meaning for the determination of the local cerebral blood flow. Pfluegers Arch. 320: 111–119, 1970.
 86. Teorell, T. Kinetics of distribution of substances administered to the body. Arch. Int. Pharmacodyn. Ther. 57: 205–224, 1944.
 87. Tonnesen, K. H. Simultaneous measurement of the calf blood flow by strain‐gauge plethysmography and the calf muscle blood flow measured by 133xenon clearance. Scand. J. Clin. Lab. Invest. 21: 65–76, 1968.
 88. Tonnesen, K. H., and P. Sejrsen. Inert gas diffusion method for measurement of blood flow. Circ. Res. 20: 552–564, 1967.
 89. Tonnesen, K. H., and P. Sejrsen. Washout of 133xenon after intramuscular injection and direct measurement of blood flow in skeletal muscle. Scand. J. Clin. Lab. Invest. 25: 71–81, 1970.
 90. Von Schrotter, H. Der Sauerstoff in der Prophylaxe und Therapie der Luftdruckerkrankungen in M. Michaelis. In: Handbuch der Sauerstofftherapie, edited by V. A. Hirschwald. Berlin. 1906, p. 155.
 91. Waud, B. E., and D. R. Waud. Calculate kinetics of distribution of nitrous oxide and methoxyflurane during intermittent administration in obstetrics. Anesthesiology 32: 306–316, 1970.
 92. Yeh, S.‐Y., and R. E. Peterson. Solubility of krypton and xenon in blood, protein solutions, and tissue homogenates. J. Appl. Physiol. 20: 1041–1047, 1965.
 93. Young, I. H., and P. D. Wagner. Solubility of inert gases in homogenates of canine lung tissue. J. Appl. Physiol. 46: 1207–1210, 1979.
 94. Zierler, K. L. Equations for measuring blood flow by external monitoring of radioisotopes. Circ. Res. 16: 309–321, 1965.
 95. Zuntz, N. Zur Pathogenese und Therapie der durch rasche Luftdruckanderungen Erzeugten. Fortschr. Med. 15: 632–639, 1897.
 96. Zwart, A., N. T. Smith, and J. E. W. Beneken. Multiple model approach to uptake and distribution of halothane: the use of an analog computer. Comput. Biomed. Res. 5: 228–238, 1972.

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Peter D. Wagner. Peripheral Inert‐Gas Exchange. Compr Physiol 2011, Supplement 13: Handbook of Physiology, The Respiratory System, Gas Exchange: 257-281. First published in print 1987. doi: 10.1002/cphy.cp030414