INHIBITION OF SARCOLEMMAL NA-ATPASE ACTIVITY REDUCES THE INFARCT SIZE-LIMITING EFFECT OF PRECONDITIONING IN RABBIT HEARTS(,K+)

Background The inhibition of sarcolemmal Na+,K+-ATPase activity is clo sely related to ischemic myocardial cell injury. However, the involvem ent of this enzyme in preconditioning has not been determined. Methods and Results We assessed the effect of ischemia on sarcolemmal Na+,K+- ATPase activity. Control and preconditioned rabbits were subjected to 0, 10, 20, 30, and 60 minutes of coronary occlusion. Ten to 60 minutes of ischemia reduced Na+,K+-ATPase activity, whereas preconditioning p reserved the activity of this enzyme only during the first 20 minutes of ischemia. To determine whether the preservation of Na+,K+-ATPase ac tivity in the early phase of ischemia contributed to limiting the infa rct size, additional rabbits underwent 30 minutes of occlusion followe d by 3 hours of reperfusion with or without pretreatment with digoxin, an inhibitor of Na+,K+-ATPase. Infarct size in animals pretreated wit h digoxin in the absence of preconditioning did not differ from that i n controls. It was markedly reduced by preconditioning, whereas digoxi n reduced the infarct size-limiting effect. Moreover, preconditioning increased sarcolemmal Na+-Ca2+ exchange activity in rabbits subjected to 20 minutes of ischemia, whereas digoxin diminished this increase. C onclusions Preconditioning preserves the ischemia-induced reduction in sarcolemmal Na+,K+-ATPase activity in the early phase of ischemia in rabbit hearts. Inhibition of Na+,K+-ATPase activity reduces the infarc t size-limiting effect of preconditioning with a loss of increased Na-Ca2+ exchange activity, implying that this preservation is responsibl e for the cardioprotective effect of preconditioning.