2004 Volume 64 Issue 2 Pages 234-242
In order to suppress the intracellular calcium overload in ischemia-reperf usion injury, KB-R7943, a selective Na+/Ca2+ exchanger inhibitor was added to the preischemic perfusates and its myocardial protective effect was studied. Rat isolated perfused hearts were divided into three experimental groups which were perfused for three minutes before ischemia with the fluids containing the following : 10 μM/l KB-R7943 solution (KBR group), KCl solution with a potassium concentration adjusted to 20 mM/l (KCL group), and 10 μM/l KB-R7943 solution with 20 mM/l of potassium concentration by adding KCl (KBR-KCI group) ; the control group was made ischemic by simply blocking coronary perfusion. After normothermic ischemia for 30 minutes, the hearts were reperf used, and the recovery rates of cardiac function (heart rate [HR], left ventricular contraction [LVC], maximum left ventricular contractive force change rate [LVdc/dt], coronary flow [CF] ) and intracellular calcium concentration were measured and compared with preischemic values. For the KBR-KCl group, cardiac function was also investigated after 60-minute ischemia (KBR-KCl 60 group) . After thirty minutes reperf usion, LVC, LVdc/dt and CF in the KBR, KBR-KCl and KBR-KCl 60 groups showed good recovery compared to those of the control group. the KBR-KCl group had an even better recovery in LVC, LVdc/ dt and CF than in the KBR group 30 minutes after perfusion. There were no significant differences among the measurements of the KBR-KCl and KBR-KCl 60 groups. For the kinetics of intracellular calcium, no intracellular calcium overload during ischemia-reperf usion was observed for the KBR-KCl and KBR groups compared to the control and KCl groups. Administration of KB-R7943 before ischemia suppressed intracellular calcium overload during ischemia-reperf usion and reduced ischemic-reperfusion injury. These results suggest that the addition of KB-R7943 to cardioplegia could have a cardioprotect effect against ischemicreperfusion injury.
