Improvement of Cardiac Function by Polyclonal Antibodies Against Ca2+/Mg2+ ecto-ATPase in Hearts Subjected to Ischemia-Reperfusion

Delayed reperfusion of an ischemic heart is known to impair the recovery of cardiac function, and the occurrence of intracellular Ca2+ overload in the myocardium is considered to play a critical role in the development of ischemia-reperfusion (I/R) injury. Since Ca2+/Mg2+ ecto-ATPase, which is activated by millimolar concentrations of Ca2+ or Mg2+, has been shown to serve as a Ca2+ gating mechanism for the entry of Ca2+ and subsequent development of intracellular Ca2+ overload, we investigated the role of depression in Ca2+/Mg2+ ecto-ATPase activity by polyclonal antibodies against Ca2+/Mg2+ 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 Ca2+-ATPase and Mg2+-ATPase activities. Pretreatment of hearts with immune serum or purified antibodies was observed to improve the recovery of cardiac function and depress the SL Ca2+/Mg2+ ecto-ATPase activities in hearts subjected to I/R injury. A marked increase in myocardial Ca2+ 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 Ca2+ concentration. These results suggest that improvement in the recovery of cardiac function in hearts subjected to I/R injury by polyclonal Ca2+/Mg2+ ecto-ATPase antibodies may be due to the attenuation of intracellular Ca2+ overload.