[Mechanism of ventilatory and heart-rate responses during sustained hypoxia in humans--role of endogenous adenosine].

To investigate whether lung stretch reflex modulates heart rate (HR) responses during hypoxia in humans, we measured ventilatory and HR responses to isocapnic progressive hypoxia and subsequent sustained hypoxia (arterial O2 saturation (SaO2); 80%, 20 min) in 22 healthy young adults. Moreover, to examine the role of endogenous adenosine in hypoxic ventilatory and HR responses in 9 of 22 subjects, a hypoxic challenge with or without dipyridamole pretreatment, an adenosine uptake blocker, was performed in a double-blind crossover fashion. Heart rate showed a biphasic change during the hypoxic challenge similar to that of ventilation. Values of HR response to isocapnic progressive hypoxia (delta HR/delta SaO2) did not correlate with those of ventilatory response (delta VE/delta SaO2) (r = 0.38, NS). HR declines (the difference between 0-2 min and 18-20 min period of sustained hypoxia) also did not show any correlation with ventilatory decline (r = 0.31, NS). delta HR/delta SaO2 with dipyridamole was smaller than that of control in 7 of 9 subjects, though not reached a statistical significance as whole data. On the other hand, delta VE/delta SaO2 was significantly enhanced from -0.35 +/- 0.13 L/min/% to -0.70 +/- 0.25 L/min/% with dipyridamole (p < 0.05). As well as ventilatory decline during sustained hypoxia, which was completed earlier with dipyridamole than with control, HR decline was significantly affected with dipyridamole. There were no changes in blood pressure during hypoxic exposure except for a slight decrease in diastolic pressure at the end of sustained hypoxia in the control study. Accordingly we concluded that there was little effect of pulmonary stretch reflex on heart rate modulation during mild hypoxia in humans and that endogenous adenosine plays a modulating role more in ventilatory change during not only acute but also sustained hypoxia than in HR change.