Mitochondrial ATP dependent potassium channels (mKATP) openers such as diazoxide (Dx) and the permeability transition pore (PTP) desensitizers such as cyclosporin A (CsA) have been constantly associated with cardioprotection at reperfusion both in vivo and in vitro experimental settings. The present study investigated the effects of Dx (100 microM/L), CsA (0.2 microM/L) and their association at reperfusion on infarct size and contractile function recovery in Langendorff perfused rat hearts subjected to 30 min of global ischemia (I) and 60 min of reperfusion (R). Postischemic recovery of left ventricular function was assessed by the rate pressure product (left ventricular developed pressure x heart rate) and by the maximal and minimal first derivatives of left ventricular pressure (dLVP/dtmax and dLVP/dtmin) as indices of contractility and relaxation, respectively. Infarct size was quantified by the 2.3.5-triphenyltetrazolium chloride staining and by the LDH leakage in the coronary effluent. At the end of reperfusion the cardioprotective drugs elicited uncoupling effects with respect to mechanical function and infarct size. A marked reduction in infarct size was obtained in Dx treated group (15 ± 3% vs. 41 ± 4% in control group, p< 0.05) without a significant increase in +dP/dtmax. Conversely, CsA lowered infarct size only by 26± 5% but induced a greater recovery of contractility. In the Dx+CsA group infarct size was also significantly (albeit not additively) reduced (20±4%, p< 0.05 vs. control) but the recovery of contractility was less important. In isolated rat hearts treated with Dx and CsA at reperfusion we report a disparity between infarct size and functional recovery. Further studies are required to elucidate the underlying mechanisms of these differential effects.

Research supported by the National Authority for Scientific Research grant 42-122/2008 and the RO-HU Bilateral Cooperation Project ID RO 17/2007.