Ca²⁺ sensitizer, pimobendan, attenuates myocardial injury in low-flow ischemic but not in total ischemic hearts

Whether Ca²⁺ sensitizer is beneficial in cases of ischemic myocardium is still controversial. We examined the effect of pimobendan on ischemic-reperfusion injury. Isolated SD rat hearts were subjected to 30 minutes of low-flow ischemia (LF) or 25 minutes of total ischemia (TI) after 10 minutes of preperfusion, and were followed by 30 minutes of reperfusion. In another two groups we used 50μM of pimobendan during LF (LFp) or 10 minutes preperfusion before TI (TIp). LV systolic pressure (62.4 % vs 93.6 % of each control value), developed pressure (57.0 % vs 95.3 %), and peak positive dp/dt (53.2 % vs 97.3 %) recovered better with reduced release of CK (458.7 vs 122.1 IU/g dwt) in the LFp group than in the LF group. ATP, creatine phosphate (CP) and lactate after reperfusion were the same in both the LF and the LFp group. Although there was no difference in recovery of LV function between the TI and TIp groups, recovery of CP decreased and ⁴⁵Ca²⁺ uptake and release of CK were greater in the TI group. In hearts with low-flow ischemia and reperfusion, pimobendan enhanced recovery of LV function without deterioration of energy metabolism or Ca²⁺ overload. These results suggest that pimobendan may be beneficial for less severe ischemia causing myocardial stunning or hibernation but not for more severe ischemia resulting in irreversible injury.