Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man

Abstract

In order to analyze the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2 +/- 2.9 mmHg/4.7 +/- 0.4 kPa) in a low-pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system.

Phase I dynamics of cardiac output, systemic O2 delivery, and lung O2 uptake at exercise onset in men in acute normobaric hypoxia

“…This hypothesis implies that phase I would be either absent or eventually less intense compared with normoxia. The main finding of this study is that the amplitude of the phase I (A 1 ) of the kinetics of Q and Q a O 2 at exercise onset was smaller in acute normobaric hypoxia, wherein reduced vagal activity (8,26) and increased sympathetic activity at rest have been postulated (21,26,58,59), than in normoxia, whereas its time constant 1 was unchanged. No differences appeared concerning the phase I of V O 2 kinetics.…”

“…In fact, the fast component of f H kinetics 1) was cancelled out under vagal blockade (18) and 2) was not found in heart transplant recipients, whose hearts are denervated (3,20,40). To extend this hypothesis to explain phase I kinetics of Q , Q a O 2 , and V O 2 , we should be able to demonstrate that when vagal tone is attenuated, as is the case in acute normobaric hypoxia (26), the phase I should either be reduced or disappear for all these parameters. Indeed, hypoxia reduced A 1 significantly, for Q and Q a O 2 (Table 3) at both 50 and 100 W and for f H at 50 W, but did not extinguish it.…”

“…In this study, we tested the hypothesis that vagal withdrawal also plays a major role in determining phase I kinetics of Q , Q a O 2 , and V O 2 . If this is so, then in acute normobaric hypoxia, wherein reduced vagal activity (8,26) and increased sympathetic activity at rest have been postulated (21,26,58,59), phase I would be either absent or at least less intense compared with normoxia.With this hypothesis in mind, the aim of this study was to perform simultaneous determinations of the phase I kinetics of f H , Q , Q a O 2 , and V O 2 upon exercise onset in normoxia and acute normobaric hypoxia. Such an experiment was never carried out in the past, to the best of our knowledge.…”

Cardiovascular effects of 8 h of isocapnic hypoxia with and without beta-blockade in humans

“…From the above, it seems likely that sympathetic mechanisms play only a minor role in the hypoxic modulation of heart rate. Other alternative mechanisms that might underlie the progressive rise in heart rate with sustained hypoxia include the possibility that the rise in heart rate is effected by a direct action of hypoxia on the heart and that the rise is effected by a withdrawal of parasympathetic activity, as is the case for the majority of the response of heart rate to acute variations in the level of hypoxia (Petersen et al 1974;Koller et al 1988). If the mechanism does involve a withdrawal of parasympathetic tone, there are also questions relating to where the hypoxia is being sensed, and whether the effect arises directly or indirectly via changes in ventilation, for example acting via afferents from the pulmonary stretch receptors (see Daly, 1986 andLooga, 1997 for details).…”

Increased myocardial blood flow during acute exposure to simulated altitudes

“…The ECG changes have mainly been attributed to the synergistic effects of catecholamine secretion and vagal withdrawal rather than to direct hypoxic effects. 2 In patients with marginal cardiocirculatory reserve or coronary artery disease (CAD), these effects may cause cardiac decompensation 3 and silent ischemia during normal daily activities, even at a modest altitude of 2000 m. 4 Thus it is current clinical practice to advise patients with CAD not to exceed moderate altitudes of about 2000 to 2500 m. [5][6][7] Similar conditions are encountered in most airplanes during flight, raising some concerns about the risk of air travel for patients with CAD. 8,9 In experimental animals, acute hypoxemia 10 and chronic hypoxemia have been shown to increase baseline 11 and maximal drug-induced 12 and exerciseinduced 11 myocardial blood flow (MBF).…”