Redistribution of Pulmonary Blood Flow during Hypoxic Exercise

Pulmonary blood flow (PBF) distribution was studied at rest and during exercise in rats acclimatized to chronic hypoxia (barometric pressure [PB] 370 Torr for 3 weeks, A rats) and non-acclimatized (NA) littermates. Both A and NA rats exercised in hypoxia (inspired O₂ pressure [PIO₂] ∼70 Torr) or in normoxia (PIO₂ ∼ 145 Torr). PBF distribution was determined using fluorescent-labeled microspheres injected into the right atrium. The lungs were cut into 28 samples to determine relative scatter of specific PBF ([sample fluorescence intensity/sample dry weight)/(total lung fluorescence intensity/total lung dry weight]). Exercise produced redistribution of PBF both in NA and A rats, and this effect was larger in hypoxia than in normoxia, with minimal redistribution occurring during normoxic exercise in NA rats. The pattern of distribution varies considerably among individual animals. As a result of distribution, the previous high flow areas would be overperfused during hypoxic exercise in some rats. The results support the concept that hypoxic pulmonary vasoconstriction is not uniform and suggest that the combination of hypoxia and exercise may lead to overperfusion and capillary leak in some individuals.

Hypoxic pulmonary vasoconstriction, high altitude pulmonary edema, microspheres, Sprague-Dawley rat.

References

• 1 Bernard S L, Glenny R W, Erickson H H, Fedde M R, Polissar N, Basaraba R J, Hlastala M P. Minimal redistribution of pulmonary blood flow with exercise in racehorses.  J Appl Physiol. 1996;  81 1062-1070
• 2 Erickson H H, Bernard S L, Glenny R W, Fedde M R, Polissar N, Basaraba R J, Walther S M, Gaughan E M, McMurphy R, Hlastala M P. Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses.  J Appl Physiol. 1999;  86 2034-2043
• 3 Fishman A P. Hypoxia on pulmonary circulation.  Circ Res. 1976;  38 221-231
• 4 Glenny R W, Lamm W JE, Albert R K, Robertson H T. Gravity is a minor determinant of pulmonary blood flow distribution.  J Appl Physiol. 1991;  71 620-629
• 5 Glenny R W, Polissar L, Robertson H T. Relative contribution of gravity to pulmonary perfusion heterogeneity.  J Appl Physiol. 1991;  71 2449-2452
• 6 Glenny R W, Bernard S, Brinkley M. Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion.  J Appl Physiol. 1993;  74 2585-2597
• 7 Mann C M, Domino K B, Walther S M, Glenny R W, Polissar N L, Hlastala M P. Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs.  J Appl Physiol. 1998;  84 2010-2019
• 8 Gonzalez N C, Clancy R L, Wagner P D. Determinants of maximal oxygen uptake in rats acclimatized to simulated altitude.  J Appl Physiol. 1993;  75 1608-1614
• 9 Gonzalez N C, Perry K, Moue Y, Clancy R L, Piiper J. Pulmonary gas exchange during hypoxic exercise in the rat.  Respir Physiol. 1994;  96 111-125
• 10 Grover R F, Weil J V, Reeves J T. Cardiovascular adaptations to exercise at high altitude.  Exerc Sport Sci Rev. 1986;  14 269-302
• 11 Groves B M, Reeves J T, Sutton J R, Wagner P D, Cymerman A, Malconian M K, Rock P B, Young P M, Houston C S. Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen.  J Appl Physiol. 1987;  63 521-530
• 12 Hakim T S, Lisbona R, Michel R P, Dean G W. Role of vasoconstriction in gravity-nondependent central-peripheral gradient in pulmonary blood flow.  J Appl Physiol. 1993;  74 897-904
• 13 Hlastala M P, Chornuk M A, Self D A, Kallas H J, Burns J W, Bernard S, Polissar N L, Glenny R W. Pulmonary blood flow redistribution by increased gravitational force.  J Appl Physiol. 1998;  84 1278-1288
• 14 Hughes J MB. Distribution of pulmonary blood flow. In: Crystal RG, West JB, Weibel E, Barnes PJ (eds) The Lung: Scientific Foundations. Philadelphia; Lippincott-Raven Publishers 1997 second edition, Vol. 2.: 1523-1536
• 15 Hultgren H N. High altitude pulmonary edema: hemodynamic aspects.  Int J Sports Med. 1997;  18 20-25
• 16 Kuwahira I, Moue Y, Ohta Y, Mori H, Gonzalez N C. Distribution of pulmonary blood flow in conscious resting rats.  Respir Physiol. 1994;  97 309-321
• 17 Kuwahira I, Moue Y, Ohta Y, Gonzalez N C. Chronic hypoxia decreases heterogeneity of pulmonary blood flow distribution in rats.  Respir Physiol. 1996;  104 205-212
• 18 McCanse W, Henderson K, Urano T, Kuwahira I, Clancy R L, Gonzalez N C. Effect of chronic sodium cyanate administration on O₂ transport and uptake in hypoxic and normoxic exercise.  J Appl Physiol. 1999;  86 1257-1263
• 19 Piiper J, Scheid P. Model for capillary-alveolar equilibration with special reference to 0₂ uptake in hypoxia.  Respir Physiol. 1981;  46 193-208
• 20 Reid L. Structure and function in pulmonary hypertension, new perceptions.  Chest. 1986;  89 279-288
• 21 Sardella G L, Ou L C. Chronically instrumented rat model for hemodynamic studies of both pulmonary and systemic circulations.  J Appl Physiol. 1993;  74 849-852
• 22 Stelzner T J, O’Brien R F, Sato K, Weil J V. Hypoxia-induced increases in pulmonary transvascular protein escape in rats: modulation by glucocorticoids.  J Clin Invest. 1988;  82 1840-1847
• 23 von Euler U S, Liljestrand G. Observations on the pulmonary arterial blood pressure in the cat.  Acta Physiol Scand. 1946;  12 301-320
• 24 Wagner P D, Gale G E, Moon R E, Torre-Bueno J R, Stolp B W, Saltzman H A. Pulmonary gas exchange in humans exercising at sea level and simulated altitude.  J Appl Physiol. 1986;  61 260-270
• 25 West JB  (ed). Regional Differences in the Lung. New York; Academic Press 1977: 85-165
• 26 West J B, Colice G L, Lee Y -J, Namba Y, Kurdak S S, Fu Z, Ou L C, Mathieu-Costello O. Pathogenesis of high-altitude pulmonary oedema: direct evidence of stress failure of pulmonary capillaries.  Eur Respir J. 1995;  8 523-529
• 27 Wood J G, Mattioli L F, Gonzalez N C. Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats.  J Appl Physiol. 1999;  87 873-881