Cardiac and respiratory effects of digitalis during chronic hypoxia in intact conscious dogs

Abstract

The arrhythmogenic and respiratory effects of ouabain during chronic hypoxia were studied in 10 unanesthetized dogs in a hypobaric chamber (446 mmHg) following 7-19 (mean 14.7) days of continuous exposure at this altitude. Another 15 dogs studied at sea level comprised the normoxic control group. In both groups, a 7.5-mug/kg loading dose of ouabain was followed by infusion of ouabain at 3.0 mug/kg per min to ECG evidence of toxicity. Mean arterial Po2 was 46 +/- 5 mmHg in chronically hypoxic dogs as compared to 86 +/- 7 mmHg in normoxic animals (P less than 0.001). Mean hematocrit was 54 +/- 1% in hypoxic and 43 +/- 2% in normoxic groups (P less than 0.001). In five dogs studied first at sea level and subsequently under conditions of chronic hypoxia, mean maximum left ventricular dP/dt and peak (dP/dt)P-1 were unchanged. Marked hyperventilation during ouabain infusion was observed. In normoxic dogs mean arterial pH rose from 7.43 +/- 0.05 to 7.70 +/- 0.02 U, and Pco2 fell from 41 +/- 4 to 15 +/- 1 mmHg during ouabain administration (P less than 0.001). Similar changes were observed in hypoxic dogs. There was no significant difference in the mean toxic dose of ouabain in chronically hypoxic (71 +/- 11 mug/kg) versus normoxic (78 +/- 12 mug/kg) animals. Thus, in contrast to acute hypoxia, chronic hypoxia in unanesthetized dogs was not associated with a significant reduction in the dose of ouabain required to produce toxic arrhythmias. Chronic hypoxia was also not associated with alterations in left ventricular performance.