Abstract

Ouabain-induced increases in contractility were measured on isolated perfused cat and rabbit hearts. At peak inotropism, Na⁺, K⁺-adenosine triphosphatase (Na⁺, K⁺-ATPase) of cat heart was inhibited compared to control, while at peak inotropism, rabbit heart Na⁺, K⁺-ATPase remained at control levels. Infusion and isolation studies using ³H-ouabain indicated that even though ³H-ouabain was present in both rabbit and cat myocardia at peak inotropism, most of the drug dissociated from the rabbit heart enzyme during isolation but remained bound to the cat heart enzyme. Studies also indicated that the inotropic effect disappeared much more readily from rabbit hearts than cat hearts after washing. In the latter case, a return to control level of contractility was coincident with a return to control levels of Na⁺,K⁺-ATPase activity. Such studies were not possible with rabbit Na⁺, K⁺-ATPase since enzyme activity from inotropic hearts was the same as control activity due to drug washoff during isolation. In vitro binding studies of ³H-ouabain to both cat and rabbit cardiac Na⁺, K⁺-ATPase indicated that the stability of the drug-enzyme complex was much higher with cat enzyme than rabbit, consistent with both pharmacologic washout data and drug dissociation during Na⁺,K⁺,-ATPase preparation. Such studies suggest that species sensitive to cardiac glycosides should be used to correlate pharmacologic with biochemical effects of certain cardiac glycosides.