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.