The Na+/Ca2+ exchanger as a culprit of myocardial stunning.

Our objective was to assess the participation of Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX) on systolic and diastolic alterations of myocardi al stunning. Isolated perfused rat hearts were submitted to 20 min of globa l ischemia (Is) followed by 30 min of reperfusion (R). This protocol was re peated after treatment before ischemia and/or early in R. with HOE 642 1 mu M, a specific blocker of NHE-1 and KB-R7943 1 muM the novel inhibitor of th e reverse mode of NCX. In control ischemic hearts the contractility assesse d through +dP/dt(max) recovered approximately 60%. When the NHE blockade wa s performed before Is or early in R the postischemic recovery reached 100%. The blockade of the reverse mode of NCX only improved significantly the re covery when administered before Is and early in R (95 +/- 7%). The ischemic contracture decreased when the treatment with both blockers was performed before Is. During R the increase of end diastolic pressure (EDP) observed i n control ischemic hearts (at 30 min of R, EDP value was 44 +/- 4 mmHg) dim inished significantly by NHE (24 +/- 6 and 12 +/- 2 mmHg when the blocker w as administered before or after Is) and NCX blockade performed before and a fter Is (12 +/- 6 mmHg). These results indicate that the activation of the reverse mode of NCX secondary to the NHE activation during ischemia and rep erfusion is the mechanism responsible for the Ca2+ overload involved in the diminution of contractility that characterizes myocardial stunning.