Benzolamide improves oxygenation and reduces acute mountain sickness during a high-altitude trek and has fewer side effects than acetazolamide at sea level.

Acetazolamide is the standard carbonic anhydrase (CA) inhibitor used for acute mountain sickness (AMS), however some of its undesirable effects are related to intracellular penetrance into many tissues, including across the blood-brain barrier. Benzolamide is a much more hydrophilic inhibitor, which nonetheless retains a strong renal action to engender a metabolic acidosis and ventilatory stimulus that improves oxygenation at high altitude and reduces AMS. We tested the effectiveness of benzolamide versus placebo in a first field study of the drug as prophylaxis for AMS during an ascent to the Everest Base Camp (5340 m). In two other studies performed at sea level to test side effect differences between acetazolamide and benzolamide, we assessed physiological actions and psychomotor side effects of two doses of acetazolamide (250 and 1000 mg) in one group of healthy subjects and in another group compared acetazolamide (500 mg), benzolamide (200 mg) and lorazepam (2 mg) as an active comparator for central nervous system (CNS) effects. At high altitude, benzolamide-treated subjects maintained better arterial oxygenation at all altitudes (3-6% higher at all altitudes above 4200 m) than placebo-treated subjects and reduced AMS severity by roughly 50%. We found benzolamide had fewer side effects, some of which are symptoms of AMS, than any of the acetazolamide doses in Studies 1 and 2, but equal physiological effects on renal function. The psychomotor side effects of acetazolamide were dose dependent. We conclude that benzolamide is very effective for AMS prophylaxis. With its lesser CNS effects, benzolamide may be superior to acetazolamide, in part, because some of the side effects of acetazolamide may contribute to and be mistaken for AMS.

Circulation time in man from lung to periphery as an indirect index of cardiac output.

Circulation time (Ct) between lung and periphery may be a surrogate for cardiac output, estimated here, for the most part, as the time between taking a breath of nitrogen and peripheral detection of a desaturation pulse. Use of pulse oximetry involves an internal, instrument delay; however, using the ear, we found shortening with exercise (12.1 +/- 0.37 sec, at rest; 9.1 +/- 0.25 sec at 100 watts), lengthening after beta-blockade, and lengthening in patients with echocardiographic and clinical left heart failure (8 patients 16.2 +/- 1.1 sec; 6 controls 12.0 +/- 0.5 sec). Pulse oximetry failed, however, to discriminate heart failure from normal in several patients. In patients referred to a department of nuclear medicine for assessment of chest pain, pulse oximetry (finger and ear) showed unacceptable variability. Nuclide delays between lung and carotid artery correlated significantly with the reciprocal of gated SPECT estimated cardiac output (Q(gs)); not so, however, for lung to finger. In normal subjects, an old Waters fast response oximeter gave short, reproducible Ct estimates and a significant correlation with the reciprocal of (indirect Fick) cardiac output (Q(if)). The relationship for normal subjects was: Ct = 0.28 x 60/Q(if) + 2.8 sec (Q(if) in L min.; P slope < .001).