RESUMEN
Aerobic exercise capacity is decreased at altitude because of combined decreases in arterial oxygenation and in cardiac output. Hypoxic pulmonary vasoconstriction could limit cardiac output in hypoxia. We tested the hypothesis that acetazolamide could improve exercise capacity at altitude by an increased arterial oxygenation and an inhibition of hypoxic pulmonary vasoconstriction. Resting and exercise pulmonary artery pressure (Ppa) and flow (Q) (Doppler echocardiography) and exercise capacity (cardiopulmonary exercise test) were determined at sea level, 10 days after arrival on the Bolivian altiplano, at Huayna Potosi (4,700 m), and again after the intake of 250 mg acetazolamide vs. a placebo three times a day for 24 h. Acetazolamide and placebo were administered double-blind and in a random sequence. Altitude shifted Ppa/Q plots to higher pressures and decreased maximum O(2) consumption ((.)Vo(2max)). Acetazolamide had no effect on Ppa/Q plots but increased arterial O(2) saturation at rest from 84 +/- 5 to 90 +/- 3% (P < 0.05) and at exercise from 79 +/- 6 to 83 +/- 4% (P < 0.05), and O(2) consumption at the anaerobic threshold (V-slope method) from 21 +/- 5 to 25 +/- 5 ml.min(-1).kg(-1) (P < 0.01). However, acetazolamide did not affect (.)Vo(2max) (from 31 +/- 6 to 29 +/- 7 ml.kg(-1).min(-1)), and the maximum respiratory exchange ratio decreased from 1.2 +/- 0.06 to 1.05 +/- 0.03 (P < 0.001). We conclude that acetazolamide does not affect maximum exercise capacity or pulmonary hemodynamics at high altitudes. Associated changes in the respiratory exchange ratio may be due to altered CO(2) production kinetics.
Asunto(s)
Acetazolamida/farmacología , Altitud , Inhibidores de Anhidrasa Carbónica/farmacología , Tolerancia al Ejercicio/efectos de los fármacos , Ejercicio Físico , Circulación Pulmonar/efectos de los fármacos , Adolescente , Adulto , Método Doble Ciego , Tolerancia al Ejercicio/fisiología , Femenino , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/efectos de los fármacos , Circulación Pulmonar/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: Acute mountain sickness (AMS) may be an early stage of high altitude cerebral edema. If so, AMS could result from an alteration of dynamic autoregulation of cerebral blood flow resulting in overperfusion of capillaries and vasogenic cerebral edema. METHODS: We measured middle cerebral artery blood flow velocity (Vmca) by transcranial Doppler and arterial blood pressure by finger plethysmography at 490 m and 20 hours after arrival at 4559 m in 35 volunteers who had been randomized to tadalafil, dexamethasone, or placebo in a study on the pharmacological prevention of high altitude pulmonary edema. A dynamic cerebral autoregulation index (ARI) was calculated from continuous recordings of Vmca and blood pressure during transiently induced hypotension. RESULTS: Altitude was associated with an increase in a cerebral-sensible AMS (AMS-C) score (P<0.001) and with a decrease in arterial oxygen saturation (Sao2), whereas average Vmca or ARI did not change. However, at altitude, the subjects with the lowest ARI combined with the lowest Sao2 presented with the highest AMS-C score (P<0.03). In addition, a stepwise multiple linear regression analysis on arterial Pco2, Sao2, and baseline or altitude ARI identified altitude ARI as the only significant predictor of the AMS-C score (P=0.01). The AMS-C score was lower in dexamethasone-treated subjects compared with high altitude pulmonary edema-susceptible untreated subjects. Neither tadalafil nor dexamethasone had any significant effect on Vmca or ARI. CONCLUSIONS: High altitude hypoxia is associated with impairment in the regulation of the cerebral circulation that might play a role in AMS pathogenesis.