Beller G A, Giamber S R, Saltz S B, Smith T W
Am J Physiol. 1975 Aug;229(2):270-4. doi: 10.1152/ajplegacy.1975.229.2.270.
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.
在低压舱（446 mmHg）中，对10只未麻醉的犬进行了7 - 19天（平均14.7天）的持续暴露于该海拔高度后，研究了慢性低氧血症期间哇巴因的致心律失常作用和呼吸效应。在海平面研究的另外15只犬组成了常氧对照组。在两组中，先给予7.5 μg/kg的哇巴因负荷剂量，然后以3.0 μg/kg每分钟的速度输注哇巴因，直至出现心电图毒性证据。慢性低氧犬的平均动脉血氧分压为46±5 mmHg，而常氧动物为86±7 mmHg（P＜0.001）。低氧组的平均血细胞比容为54±1%，常氧组为43±2%（P＜0.001）。在5只先在海平面研究随后在慢性低氧条件下研究的犬中，平均最大左心室dP/dt和峰值（dP/dt）P - 1未改变。在输注哇巴因期间观察到明显的过度通气。在常氧犬中，在给予哇巴因期间，平均动脉pH从7.43±0.05升至7.70±0.02 U，Pco2从41±4降至15±1 mmHg（P＜0.001）。在低氧犬中观察到类似变化。慢性低氧犬（平均中毒剂量为71±11 μg/kg）与常氧犬（平均中毒剂量为78±12 μg/kg）的哇巴因平均中毒剂量无显著差异。因此，与急性低氧不同，未麻醉犬的慢性低氧与产生毒性心律失常所需的哇巴因剂量显著降低无关。慢性低氧也与左心室功能改变无关。
