Comparable Cardioprotection at Reperfusion by Magnesium Orotate and Cyclosporin A: A Study in Isolated Rat Hearts

Abstract

Orotic acid and its salts has been previously shown to improve the energy status of cardiomyocytes and to protect myocardium following transplantation and cardioplegic arrest. The present study carried out in Langendorff perfused rat hearts was purported to compare cardioprotection elicited by CsA with the one afforded by magnesium orotate (Mg-O) when administrated at reperfusion. To this aim isolated rat hearts (n = 6-8/group) subjected to 30 min of global ischemia and 30 min of reperfusion were randomized to receive: (1) no intervention (Controls), (2) Mg-O (1 mM) and (3) CsA (0.2 μM) in the perfusion buffer throughout the reperfusion period. Recovery of post-ischemic ventricular function was assessed by the left ventricular developed pressure (LVDP), rate pressure product (RPP), and maximal and minimal first derivatives of left ventricular pressure (dLVP/dtmax and dLVP/dtmin) as indices of contractility and relaxation, respectively. All contractile parameters were expressed as percentage of their pre-ischemic values. At the end of the reperfusion period, both Mg-O and CsA induced a substantial recovery of contractile function parameters. Accordingly, LVDP was 59.4 ± 2.24% and 65.8 ± 1.56% in Mg-O and CsA groups, respectively vs. 36 ± 3.68% in Controls (p < 0.001). Similarly, both Mg-O and CsA administration improved contractility (59,4 ± 2.24% and 65.97 ± 1,6%, p=NS) and relaxation indices (67,6 ± 0,8% and 65,8 ± 1,5%, p=NS) when compared to Controls (p < 0.001). In isolated rat hearts, acute administration of Mg-O and CsA at reperfusion was associated with significant improvement of the postischemic contractile function.