Abstract
Delayed reperfusion of an ischemic heart is known to impair the recovery of cardiac function, and the occurrence of intracellular Ca(2+) overload in the myocardium is considered to play a critical role in the development of ischemia-reperfusion (I/R) injury. Since Ca(2+)/Mg(2+) ecto-ATPase, which is activated by millimolar concentrations of Ca(2+) or Mg(2+), has been shown to serve as a Ca(2+) gating mechanism for the entry of Ca(2+) and subsequent development of intracellular Ca(2+) overload, we investigated the role of depression in Ca(2+)/Mg(2+) ecto-ATPase activity by polyclonal antibodies against Ca(2+)/Mg(2+) ecto-ATPase in promoting the recovery of cardiac function in isolated perfused rat hearts upon subjection to I/R injury. Incubation of sarcolemma (SL) membranes with immune serum or purified IgG antibody fraction was found to depress both Ca(2+)-ATPase and Mg(2+)-ATPase activities. Pretreatment of hearts with immune serum or purified antibodies was observed to improve the recovery of cardiac function and depress the SL Ca(2+)/Mg(2+) ecto-ATPase activities in hearts subjected to I/R injury. A marked increase in myocardial Ca(2+) content in I/R hearts was also attenuated by immune serum treatment. Furthermore, treatment of cardiomyocytes from normal hearts with immune serum or purified antibodies reduced the ATP-induced increase in intracellular Ca(2+) concentration. These results suggest that improvement in the recovery of cardiac function in hearts subjected to I/R injury by polyclonal Ca(2+)/Mg(2+) ecto-ATPase antibodies may be due to the attenuation of intracellular Ca(2+) overload.