After acclimatization to high altitude, maximal exercise cardiac output (Q˙t) is reduced. Possible contributing factors include 1) blood volume depletion, 2) increased blood viscosity, 3) myocardial hypoxia, 4) altered autonomic nervous system (ANS) function affecting maximal heart rate (HR), and 5) reduced flow demand from reduced muscle work capability. We tested the role of the ANS reduction of HR in this phenomenon in five normal subjects by separately blocking the sympathetic and parasympathetic arms of the ANS during maximal exercise after 2-wk acclimatization at 3,800 m to alter maximal HR. We used intravenous doses of 8.0 mg of propranolol and 0.8 mg of glycopyrrolate, respectively. At altitude, peak HR was 170 ± 6 beats/min, reduced from 186 ± 3 beats/min ( P = 0.012) at sea level. Propranolol further reduced peak HR to 139 ± 2 beats/min ( P = 0.001), whereas glycopyrrolate increased peak HR to sea level values, 184 ± 3 beats/min, confirming adequate dosing with each drug. In contrast, peak O2 consumption, work rate, and Q˙t were similar at altitude under all drug treatments [peak Q˙t = 16.2 ± 1.2 (control), 15.5 ± 1.3 (propranolol), and 16.2 ± 1.1 l/min (glycopyrrolate)]. All Q˙t results at altitude were lower than those at sea level (20.0 ± 1.8 l/min in air). Therefore, this study suggests that, whereas the ANS may affect HR at altitude, peak Q˙t is unaffected by ANS blockade. We conclude that the effect of altered ANS function on HR is not the cause of the reduced maximal Q˙t at altitude.
THE ROLE OF VOLUME DEPLETION IN FUROSEMIDE ENHANCED AMINOGLYCOSIDE NEPHROTOXICITY
