.1.Sports SportsMed. Med.13(1992) 13(1992) S27 S27 mt. J.

Reflex Control ofthe Circulation during Exercise

Rowell L. B., Brengelmann G. L., Freund P. R.: Unaltered

tional stress like heat or hypoxemia raises HR above 100 beats mm — '(work rate and V02 are unchanged). Plasma norepine-

norepinephrine: heart rate relationship in exercise with exogenous heat.JApplPhysiol62: 646—650,1987.

phrine (NE) concentration (an index of SNA) begins to rise the slope remarkedly when HR exceeds 100 beats min lating NE concentration to HR remains unchanged (2, 3). Stated differently, SNA increases to the same degree at any given HR, but the V02 and work rate at which SNA rises is

In conclusion, the upward resetting of the arterial baroreflex and the differing speeds of parasympathetic vs. sympathetic responses to mild vs. moderate exercise could explain why virtually all organs receive increased SNA at such low levels of exercise after vagal withdrawal is complete and while muscle chemoreflexes are still inactive. References

2

Houk J. C.: Control strategies in physiological systems. FASEB J 2:97—107,1988. Rowell L. B.: Human Circulation. Regulation during Physical Stress. New York, Oxford University Press, 1986.

during exercise: chemoreflexes and mechanoreflexes. JAppI Physio169:407—418, 1990.

Rowell L. B., Savage M. V., Chambers J., Blackmon, J. R.: Cardiovascular responses to graded reductions in leg perfusion in exercising humans. Am JPhysiol26 1 (Heart CircPhysiol 30): Hi 545— H1553, 1991. Seals D. S., Victor R. G.: Regulation of muscle sympathetic nerve activity during exercise in humans, in Holloszy J. 0. (ed): Exercise

6

and Sport Sciences Reviews. Baltimore, Williams and Wilkins, l99l,pp3l3—349.

8

Sheriff D. D., Wyss C. R., Rowell L. B., Scher A. M.: Does inadequate oxygen delivery trigger pressor response to muscle hypoperfusion during exercise? Am J Physiol 253 (Heart Circ Physiol 2t): HI 199—H1207,l987. Strange S., Rowell L. B., Christensen N. J., Saltin B.: Cardiovascu-

lar responses to carotid sinus baroreceptor stimulation during

moderate to severe exercise in man. Acta Physiol Scand 138: 145— 153, 1990.

LoringB. Rowell Department of Physiology and Biophysics and of Medicine University of Washington School of Medicine Seattle, WA 98i95,U. S. A.

Pulmonary Circulation in Hypoxia Robert Naee Robert Naejje Laboratory of Cardiovascular and Respiratory Physiology, Erasme Hospital, Free University of Brussels, Belgium

Abstract Robert Naeije, Pulmonary Circulation in Hy1992. poxia. IntJ mt J Sports Sports Med, Mcd, Vol Vol 13, 13, Suppl Suppi 1, 1, pp pp S27—S30, S27—S30, 1992.

Hypoxia vessels. Hypoxia constricts the pulmonary vessels. An increase in pulmonary pulmonary vascular vascular resistance resistance isis seen seen in innornormal subjects during hypoxic hypoxic breathing breathing at at sea sea level, level, in in accliacclimatized lowlanders and in in high high altitude altitude natives. natives. Hypoxic Hypoxic pulmonary hypertension in all these circumstances is most generally moderate, except in high altitude natives at exercise. However, in the absence of high altitude pulmonary edema (HAPE) or chronic mountain sickness, a right heart failure that would be the human counterpart of brisket disease described in cattle, apparently never occurs. In adult patients with HAPE, reported mean pulmonary artery pressures (Ppa) measured during during aa right right heart heart catheterization catheterization Tnt. J. Sports Med. 13(1992) S27—S30 527—S30

GeorgThieme Verlag Stuttgart New York

range from 22 to 63 mmHg mmHg with with an an average average of of 39 39 mmHg. mmHg. Recent echo-Doppler estimates of systolic Ppa in patients with a HAPE are at an average of 53 mmHg, only moderately higher than in healthy healthy subjects subjects exposed exposed to to comcomparable normobaric or hypobaric hypoxia. Subjects with a previous HAPE often present present with with an an enhanced enhanced pulmonary pulmonary vascular reactivity to hypoxia hypoxia compared compared to to controls controls when when tested ay sea level, but the the overlap overlap is is great. great. Non Non invasive invasive

echo-Doppler pulmonary hemodynamic studies at sea level have not been reported to reliably discriminate subjects susceptible to HAPE. Key words Key

Hypoxic pulmonary vasoconstriction, vasoconstriction, high high altitude pulmonary edema, edema, altitude altitude

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much lower with the added stress (see Figure 1). Thus whenever controlof HR shifts from the parasympat hetic to the sympathetic system, thereafter SNA increases in proportion to HR.

Rowell L. B., O'Leary D. S.: Reflex control of the circulation

528 Tnt. J. Sports Med. 13(1992)

Robert Naeje 40

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duced by an acute acute decrease decrease in in the the fraction fractionof ofinspired inspired02 02(F102) (Fl02) from 0.21 to to 0.1—0.15. 0.1—0.15. Limits Limits of of normal normalininnormoxia normoxiaand andininhypoxia hypoxiahave have been derived from measurements in 38 healthy adult volunteers challenged with a F102 of 0.125. Dots: measurements in normoxia. Triangles: measurements in hypoxia. Vertical bars: SD. N° ito 5: subjects with previous HAPE reported by Hultgren Hujtgren et al. (13); n° 6: a subject with previous HAPE reported by Penazola and Sime (22); n° 7 and 8: a subject before and after NAPE respectively, and n° 9: a subject with previous HAPE, HAPE, reported by Naeije et al. aI. (21, 20); n° 10 and 11:44 subjects with previous HAPE NAPE and 51 controls contro's respectively, reported by Viswanathan et al. (25); n° 12 and 13: 5 subjects with previous HAPE and 5 controls respectively, reported by Kawashima et al. (15); n° 15 and 16: 8 subjects subjects with previous NAPE HAPE and 6 controls respectively, reported by Yagi et al. (26). Many subjects with previous HAPE have a normal pulmonary vascular

reactivity to normobaric hypoxia.

1. Hypoxic Pulmonary Vasoconstriction at Sea Level

The first demonstration of a hypoxia-induced pulmonary vasoconstriction (HPV) was made in cats ventilated with a fraction of inspired 02 (F102) of 0.1 by von Euler and Liljestrand in 1946 (5). Only one year later, the first deal. (19). scription of HPV in man was reported by Motley et a!. These authors observed in 5S normal volunteers, acutely challenged with a F102 of 0.1, an increase in mean pulmonary artery pressure (Ppa) by 13 to 23 mmHg. The hypoxic pulmonary pressor response has since been found to occur in all tested (1 (10). vertebrate species tested 0). However, However, it varies greatly, from one species to another, and also, within a species, from one individual dividual to another (10). In a series of 38 normal subjects subjects chalchallenged with a F102 of 0.125 (arterial P02 (Pa02) 40 Torr) (Figure 1) we observed changes in Ppa ranging from 0 to 20 mmHg, in the presence of a slight 15—20% increase in cardiac output (Q) and no change in pulmonary artery wedge pressure (Ppw).

Hypoxia did not increase pulmonary vascular resistance (PVR) in 8 of these subjects. A comparable proportion of "nonresponders" has been reported in other studies on the acute effects of normobaric hypoxia in normal volunteers (9). 2. Stimulus-Response Stimulus-Response Curves Curves for for Hypoxic Hypoxic 2. Puinionary Vasoconstriction

The relationship between Ff02 or alveolar P02 (PAO2), and HPV expressed as a change in Ppa at a given flow (PAD2),

or as an amount of flow diversion at a given Ppa, has been generally found in a variety of experimental animal preparations to be either sigmoid-shape (2) or linear (8), with a continued constriction as long as F102 or PAD2 PAO2 was decreased. However, in isolated in vivo pig lungs at a constant flow, in which particular attention was paid to reach a steady state before each measurement, the Ppa: PAD2 PAO2 curve was shown to be biphasic, with a maximum at a PAO2 between 30 and 60 Torr, and a downsloping portion, portion, or or hypoxic hypoxic pulmonary pulmonaryVava-

sodilation, at lower PAD2 PAO2 (24). In dogs, a species with a pulmonary vasoreactivity to hypoxia comparable to that of man (10), the relationship between F102, progressively decreased from 1I to to 0.06, 0.06, and and Ppa measured at a constant Q, has has been shown to be biphasic as well, with a downsloping at a F102 lower than of of0.l, 0.1,corresponding correspondingto to aa Pa02of36—38Torr(4). Pa02of36—38Torr(4). Evidence of hypoxic pulmonary vasodilation in man was obtained during Operation Everest 11(9). In these studies, nor-

mal subjects decompressed in a hypobaric chamber for 40 days to a barometric pressure (Pb) equivalent to the summit of Mount Everest, presented an average Ppa of 34 mmHg at rest and of 54 mmHg at exercise at a Pb of 282 Torr (7,620 m, resting Pa02 37 Torr), that decreased to 33 and 48 mmHg respectively at a Pb of 240 Torr (8,840 m, resting Pa02 30 Torr) (9). Because of a relative hypoventilation compared to acclimatized lowlanders, high altitude natives present a resting Pa02

of 40 Torr at lower altitudes, around 4,500 m. It might be speculated that people born and living at Morococha, 4,540 m,

would be continuously exposed to HPV at its maximum strength. 3. The Function of Hypoxic Pulmonary Vasoconsfrictjon Vasoconsfriction

Von Euler and Liljestrand hypothesized that HPV would improve pulmonary gas exchange by diverting blood flow from hypoxic to better oxygenated lung regions (5). Grant et al. (8) used the equations of the control theory and

the linear relationship between lobar blood flow and PAO2 found in the coatimundi, an animal with a strong hypoxic pressor response, to calculate the efficiency of HPV as a mecha-

nism to stabilize PAO2. They found a gain due to feedback (Gfb) of a maximum of 0.9 at a PAD2 PAO2 between 60 and 80 Torr, falling rapidly off outside these values. A Gfb of 0.9 represents Vo ofthe decrease in PAO2 an active correction of 47 Yo PAD2 that that would would occur in a passive system without HPV. Mélot et al. (18) used

the same equations and linear relationships between between comcompartmental blood flow and PAD2 PAO2 derived from inert gases

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Fig. 1 Hypoxic pulmonary pressor responses at sea level, expressed as absolute increases in mean pulmonary arterial pressure (Ppa), in-

mt. J. Sports Med. 13(1992) S29

Pulmonary Circulation in Hypoxia

eases. Feeding the equations of the control theory with biphasic stimulus-response curves for HPV has not yet been done, but most likely lead to the prediction that HPY HPV actually 35—4OTorr). deteriorates gas exchange at low PAO2 (