Evidence of altered regulation of ventilation during exposure to hypoxia

Abstract

The purpose of this study was to investigate the hypothesis that ventilatory acclimatization of lowlanders to sojourn at 3100 m altitude is not due solely to a relative increase in medullary H + stimulation. The ventilatory response to the pharmacologie stimulant, doxapram hydrochloride, was measured on the same eight healthy sea-level residents during conditions of: (1) normal rest, (2) acute respiratory acidosis, (3) after 5 days of metabolic acidosis, (4) light exercise, (5) acute hypoxia (PaO 2 = 46 mm Hg) and (6) after 2–3 wk of altitude sojourn (3100 m). A seventh study was completed on seven lifelong residents of 3100 m altitude. Doxapram was infused for 20 min (0.095 mg/kg/min during isocapnic hyperoxic conditions ( P et O2 = 200 mm Hg except in [5]. The ventilatory response to doxapram did not differ significantly between conditions 1, 2, 3, 4 and 7 ( Δ dot V e = 8−13 l/min, P > 0.05 ). The response to doxapram was, however, increased by those conditions which also increase responsiveness to physiologic stimuli, specifically, acute hypoxic and altitude sojourn ( Δ dot V e = 26 1+/min, P <0.05 ). Two conclusions are warranted. First, because responsiveness was not altered by acidosis, it would seem unlikely that the increased responses are related to [H +] at any extra- or intracellular receptor. Second, during altitude sojourn the change is present even though measurements were made during acute hyperoxia; hence,'this change is separate and distinct from that of acute hypoxia. The authors postulate this change results from increased “facilitation” of the medullary ventilatory control center by the reticular activating system.