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

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.