Abstract
This review presents evidence for the recruitment of intrapulmonary arteriovenous shunts (IPAVS) during exercise in normal healthy humans. Support for pre-capillary connections between the arterial and venous circulation in lungs of humans and animals have existed for over one-hundred years. Right-to-left physiological shunt has not been detected during exercise with gas exchange-dependent techniques. However, fundamental assumptions of these techniques may not allow for measurement of a small (1–3%) anatomical shunt, the magnitude of which would explain the entire A-aDO2 typically observed during normoxic exercise. Data from contrast echocardiograph studies are presented demonstrating the development of IPAVS with exercise in 90% of subjects tested. Technetium-99m labeled macroaggregated albumin studies also found exercise IPAVS and calculated shunt to be ∼2% at max exercise. These exercise IPAVS appear strongly related to the alveolar to arterial PO2 difference, pulmonary blood flow and mean pulmonary artery pressure. Hypoxic exercise was found to induce IPAVS at lower workloads than during normoxic exercise in 50% of subjects, while all subjects continued to shunt during recovery from hypoxic exercise, but only three subjects demonstrated intrapulmonary shunt during recovery from normoxic exercise. We suggest that these previously under-appreciated intrapulmonary arteriovenous shunts develop during exercise, contributing to the impairment in gas exchange typically observed with exercise. Future work will better define the conditions for shunt recruitment as well as their physiologic consequence.
All authors contributed equally to this publication.
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References
Aviado DM, Daly MD, Lee CY and Schmidt CF. The contribution of the bronchial circulation to the venous admixture in pulmonary venous blood. J Physiol 155: 602–622, 1961.
Bachofen H, Hobi HJ and Scherrer M. Alveolar-arterial N2 gradients at rest and during exercise in healthy men of different ages. J Appl Physiol 34: 137–142, 1973.
Barzilai B, Waggoner AD, Spessert C, Picus D and Goodenberger D. Two-dimensional contrast echocardiography in the detection and follow-up of congenital pulmonary arteriovenous malformations. Am J Cardiol 68: 1507–1510, 1991.
Berk JL, Hagen JF, Tong RK and Maly G. The use of dopamine to correct the reduced cardiac output resulting from positive end-expiratory pressure. A two-edged sword. Crit Care Med 5:269, 1977.
Bogousslavsky J and Pierre P. Ischemic stroke in patients under age 45. Neurol Clin 10: 113–124, 1992.
Bracco Diagnostics Inc. Macrotec® Kit for the Preparation of Technetium Tc 99m Albumin Aggregated. 1994. New Jersey, Bracco Diagnostics Inc.
Butler BD and Hills BA. The lung as a filter for microbubbles. J Appl Physiol 47: 537–543, 1979.
Clara M. Die Arterio-Venösen Anastomosen. Vienna: Springer-Verlag, 1956.
Conhaim RL and Rodenkirch LA. Functional diameters of alveolar microvessels at high lung volume in zone II. JAppl Physiol 85: 47–52, 1998.
Conhaim RL and Staub NC. Reflection spectrophotometric measurement of O2 uptake in pulmonary arterioles of cats. JAppl Physiol 48: 848–856, 1980.
Conhaim RL, Watson KE, Heisey DM, Leverson GE and Harms BA. Perfusion heterogeneity in rat lungs assessed from the distribution of 4-microm-diameter latex particles. JAppl Physiol 94: 420–428, 2003.
Dempsey JA and Wagner PD. Exercise-induced arterial hypoxemia. JAppl Physiol 87: 1997–2006, 1999.
Di Tullio M, Sacco RL, Gopal A, Mohr JP and Homma S. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 117: 461–465, 1992.
Eldridge MW, Dempsey JA, Haverkamp HC, Lovering AT and Hokanson JS. Exercise-induced intrapulmonary arteriovenous shunting in healthy humans. JAppl Physiol 97: 797–805, 2004.
Eldridge MW, Podolsky A, Richardson RS, Johnson DH, Knight DR, Johnson EC, Hopkins SR, Michimata H, Grassi B, Feiner J, Kurdak SS, Bickler PE, Wagner PD and Severinghaus JW. Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema. JAppl Physiol 81: 911–921, 1996.
Elliott FM and Reid L. Some new facts about the pulmonary artery and its branching pattern. Clin Radiol 16: 193–198, 1965.
Foulkes MA, Wolf PA, Price TR, Mohr JP and Hier DB. The Stroke Data Bank: design, methods, and baseline characteristics. Stroke 19: 547–554, 1988.
Freeman ME, Snider GL, Brostoff P, Kimelblot S and Katz LN. Effect of training on response of cardiac output to muscular exercise in athletes. J Appl Physiol 8: 37–47, 1955.
Fritts HW, Harris P, Chidsey CAI, Clauss RH and Cournand A. Estimation of flow through bronchial-pulmonary vascular anastomoses with use of T-1824 dye. Circulation 23: 390–398, 1961.
Gledhill N, Frosese AB and Dempsey JA. Ventilation to perfusion distribution during exercise in health. In: Muscular exercise and the lung, edited by Dempsey JA and Reed CE. Madison: University of Wisconsin Press, 1977, p. 325–344.
Gudavalli A, Kalaria VG, Chen X and Schwarz KQ. Intrapulmonary arteriovenous shunt: diagnosis by saline contrast bubbles in the pulmonary veins. J Am Soc Echocardiogr 15: 1012–1014, 2002.
Hagen PT, Scholz DG and Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 59: 17–20, 1984.
Hammond MD, Gale GE, Kapitan KS, Ries A and Wagner PD. Pulmonary gas exchange in humans during exercise at sea level. J Appl Physiol 60: 1590–1598, 1986.
Hart RG and Benavente O. Stroke: part I. A clinical update on prevention. Am Fam Physician 59: 2475–82, 2485, 1999.
Hernandez A, Strauss AW, McKnight R and Hartmann AF, Jr. Diagnosis of pulmonary arteriovenous fistula by contrast echocardiography. J Pediatr 93: 258–261, 1978.
Hlastala MP. Multiple inert gas elimination technique. J Appl Physiol 56: 1–7, 1984.
Homma S, Di Tullio MR, Sacco RL, Sciacca RR, Smith C and Mohr JP. Surgical closure of patent foramen ovale in cryptogenic stroke patients. Stroke 28: 2376–2381, 1997.
Hopkins SR, McKenzie DC, Schoene RB, Glenny RW and Robertson HT. Pulmonary gas exchange during exercise in athletes. I. Ventilation-perfusion mismatch and diffusion limitation. J Appl Physiol 77: 912–917, 1994.
Jameson AG. Diffusion of gases from alveolus to precapillary arteries. Science 139: 826–828, 1963.
Jameson AG. Gaseous diffusion from alveoli into pulmonary arteries. J Appl Physiol 19: 448–456, 1964.
Kitamura K, Jorgensen CR, Gobel FL, Taylor HL and Wang Y. Hemodynamic correlates of myocardial oxygen consumption during upright exercise. J Appl Physiol 32: 516–522, 1972.
Lamy C, Giannesini C, Zuber M, Arquizan C, Meder JF, Trystram D, Coste J and Mas JL. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFO-ASA Study. Atrial Septal Aneurysm. Stroke 33: 706–711, 2002.
Lechat P, Mas JL, Lascault G, Loron P, Theard M, Klimczac M, Drobinski G, Thomas D and Grosgogeat Y. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 318: 1148–1152, 1988.
Lee WL, Graham AF, Pugash RA, Hutchison SJ, Grande P, Hyland RH and Faughnan ME. Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations. Chest 123: 351–358, 2003.
Lenfant C. Measurement of factors impairing gas exchange in man with hyperbaric pressure. J Appl Physiol 19: 189–194, 1964.
Lovering AT, Haverkamp HC, Hokanson JS, Pegelow DF, Romer LM and Eldridge MW. Quantification of Exercise-Induced Intrapulmonary Shunting in Healthy Humans. In preparation: 2006.
Lovering, A. T., Watson, K. E., Conhaim, R. L., and Eldridge, M. W. Transpulmonary passage of 15µm and 30µm polymer microspheres in rat. Program No.368.9.2005 Abstract Viewer/Itinerary Planner. San Diego, CA: Experimental Biology, 2005.Online. 2005.
Malvin GM. Gill Structure and Function, Amphibian Larvae. In: Comparative Pulmonary Physiology, edited by Wood SC. New York: Marcel Dekker, INC., 1989, p. 121–151.
Meerbaum S. Principles of echo contrast. In: Advances in echo imaging using contrast enhancement, edited by Nanda N and Schlief R. Netherlands: Kluwer, 1993, p. 9–42.
Mellemgaard K, Lassen NA and Georg J. Right-to-left shunt in normal man determined by the use of tritium and krypton 85. J Appl Physiol 15: 778–782, 1962.
Meltzer RS, Klig V and Teichholz LE. Generating precision microbubbles for use as an echocardiographic contrast agent. J Am Coll Cardiol 5: 978–982, 1985.
Meltzer RS, Tickner EG and Popp RL. Why do the lungs clear ultrasonic contrast? Ultrasound Med Biol 6: 263–269, 1980.
Overell JR, Bone I and Lees KR. Interatrial septal abnormalities and stroke: a metaanalysis of case-control studies. Neurology 55: 1172–1179, 2000.
Podolsky A, Eldridge MW, Richardson RS, Knight DR, Johnson EC, Hopkins SR, Johnson DH, Michimata H, Grassi B, Feiner J, Kurdak SS, Bickler PE, Severinghaus JW and Wagner PD. Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema. J Appl Physiol 81: 922–932, 1996.
Prinzmetal M, Ornitz ME, Simkin B and Bergman HC. Arterio-venous anastomoses in liver, spleen and lungs. Am J Physiol 152: 48–52, 1948.
Rahn H, Stroud RC and Tobin CE. Visualization of arterio-venous shunts in by cinefluorography in the lungs of normal dogs. Proc Soc Exp Biol 80: 239, 1952.
Raisinghani A and DeMaria AN. Physical principles of microbubble ultrasound contrast agents. Am J Cardiol 90(suppl): 3J–7J, 2002.
Ravin M, Epstein RM and Malm JR. Contribution of thebesian veins to the physiologic shunt in anesthetized man. J Appl Physiol 20: 1148–1152, 1965.
Reeves JT and Taylor AE. Pulmonary hemodynamics and fluid exchange in the lung during exercise. In: Handbook of Physiology: Section 12: Exercise: Regulation and Integration of Multiple Systems, edited by Rowell LB and Shephard JT. New York: Oxford University Press, 1996, p. 594–595.
Reines HD and Civetta JM. The inaccuracy of using 100% oxygen to determine intrapulmonary shunts in spite of PEEP. Crit Care Med 7: 301–303, 1979.
Rice A J, Thornton AT, Gore CJ, Scroop GC, Greville HW, Wagner H, Wagner PD and Hopkins SR. Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia. J Appl Physiol 87: 1802–1812, 1999.
Roelandt J. Contrast echocardiography. Ultrasound Med Biol 8: 471–492, 1982.
Sacco RL, Ellenberg JH, Mohr JP, Tatemichi TK, Hier DB, Price TR and Wolf PA. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 25: 382–390, 1989.
Sappey PC. Traité dánatomie descriptive. Paris: V.A. Delahaye, 1879.
Schaffartzik W, Poole DC, Derion T, Tsukimoto K, Hogan MC, Arcos JP, Bebout DE and Wagner PD. VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema. J Appl Physiol 72: 1657–1667, 1992.
Schimmel C, Bernard SL, Anderson JC, Polissar NL, Lakshminarayan S and Hlastala MP. Soluble gas exchange in the pulmonary airways of sheep. J Appl Physiol 97: 1702–1708, 2004.
Shaw AM, Bunton DC, Fisher A, McGrath JC, Montgomery I, Daly C and MacDonald A. V-shaped cushion at the origin of bovine pulmonary supernumerary arteries: structure and putative function. J Appl Physiol 87: 2348–2356, 1999.
Shub C, Tajik AJ, Seward JB and Dines DE. Detecting intrapulmonary right-to-left shunt with contrast echocardiography. Observations in a patient with diffuse pulmonary arteriovenous fistulas. Mayo Clin Proc 51: 81–84, 1976.
Sobol BJ, Bottex G, Emirgil C and Gissen H. Gaseous diffusion from alveoli to pulmonary vessels of considerable size. Circ Res 13: 71–79, 1963.
Spanner R. Die Drosselklappe der veno-venösen Anastomose und ihre Bedeuteng für den Abkürzungskreislauf im porto-cavalen System des Vogels; zugleich ein Beitrag zur Kenntnis der epitheloiden Zellen. Ztschr f Anat u Entwklsg 109: 443–492, 1939.
Stern BJ, Kittner S, Sloan M, Meyd C, Buchholz D, Rigamonti D, Woody R, Meyerhoff J, Bell W and Price T. Stroke in the young. (Part I). Md Med J 40: 453–462, 1991.
Stern BJ, Kittner S, Sloan M, Meyd C, Buchholz D, Rigamonti D, Woody R, Meyerhoff J, Bell W and Price T. Stroke in the young. Part II. Md Med J 40: 565–571, 1991.
Stickland MK, Welsh RC, Haykowsky MJ, Petersen SR, Anderson WD, Taylor DA, Bouffard M and Jones RL. Intra-pulmonary shunt and pulmonary gas exchange during exercise in humans. J Physiol 561: 321–329, 2004.
Tobin CE. Arteriovenous shunts in the peripheral pulmonary circulation in the human lung. Thorax 21: 197–204, 1966.
Torre-Bueno JR, Wagner PD, Saltzman HA, Gale GE and Moon RE. Diffusion limitation in normal humans during exercise at sea level and simulated altitude. J Appl Physiol 58: 989–995, 1985.
von Hayek H. über einen Kurzschlusskreislauf (arterio-venöse Anastomosen) in der menschlichen Lunge. Ztschr f Anat u Entwklsg 110: 412–422, 1940.
von Hayek H. The Human Lung. Translated from Die Menschliche Lunge by V.E. Krahl. New York and London: Hafner, 1960.
Wagner PD, Gale GE, Moon RE, Torre-Bueno JR, Stolp BW and Saltzman HA. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 61: 260–270, 1986.
Wagner PD, Gale GE, Moon RE, Torre-Bueno JR, Stolp BW and Saltzman HA. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 61: 260–270, 1986.
Wagner PD, Laravuso RB, Uhl RR and West JB. Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2. J Clin Invest 54: 54–68, 1974.
Weibel E. (Blood vessel anastomoses in the human lungs.). Z Zellforsch Mikrosk Anat 50: 653–692, 1959.
Weibel ER. (Morphometric analysis of the number, volume and surface of the alveoli and capillaries of the human lung). Z Zellforsch Mikrosk Anat 57: 648–666, 1962.
Weibel ER. Morphometrics of the lung. In: Handbook of Physiology Section 3: Respiration, edited by Fenn WO and Rahn H. Washington, D.C.: American Physiological Society, 1964, p. 285–307.
Whyte MK, Peters AM, Hughes JM, Henderson BL, Bellingan GJ, Jackson JE and Chilvers ER. Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations. Thorax 47: 790–796, 1992.
Wilkinson MJ and Fagan DG. Postmortem demonstration of intrapulmonary arteriovenous shunting. Arch Dis Child65: 435–437, 1990.
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Lovering, A.T., Stickland, M.K., Eldridge, M.W. (2006). Intrapulmonary Shunt During Normoxic and Hypoxic Exercise in Healthy Humans. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia and Exercise. Advances in Experimental Medicine and Biology, vol 588. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-34817-9_4
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