Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias.
The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 mug/kg per min. Significantly less AS was required to produce arrhythmias during hypoxia and hypercapnic acidosis together than during the period with normal arterial Po(2), Pco(2), and pH (10 animals). Included in this group were two animals which had undergone previous bilateral adrenalectomy and four animals in which heart rate was maintained at the same frequency during both study periods. A significant reduction in the toxic dose of AS also was demonstrated in eight animals, two with constant heart rate, during hypoxia with normal arterial Pco(2) and pH. Hypercapnic acidosis alone (eight animals) did not significantly alter the toxic dose of AS. After the administration of propranolol (six animals) or hexamethionium (six animals), no significant difference was observed between the toxic dose of AS during hypoxia and that during ventilation with room air. Thus although hypoxia and hypercapnic acidosis together do reduce the amount of AS required to produce arrhythmias, it is the hypoxia which exerts the predominant effect on the development of this increased sensitivity to AS. Furthermore, this effect of hypoxia occurs primarily as a result of reflexly augmented sympathetic stimulation of the heart.
D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000471:Alkalosis / Q000503:physiopathology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002297:Cardanolides; D002395:Catecholamines / Q000502:physiology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007263:Infusions, Parenteral; D010100:Oxygen / Q000097:blood; D011433:Propranolol / Q000494:pharmacology
D002297:Cardanolides; D002395:Catecholamines; D006584:Hexamethonium Compounds; D002245:Carbon Dioxide; D011433:Propranolol; D010100:Oxygen