Abstract 16887: Magnesium Orotate Elicits Acute Cardioprotection at Reperfusion in Isolated and in vivo Rat Hearts
Orotic acid and its salts given in chronic administration have shown significant improvement of cardiac function in several pathological settings. The aim of the present study was to investigate the effect of magnesium orotate (Mg-Or) administration at the onset of post ischemic reperfusion on myocardial function and infarct size.
Methods: Ex vivo experiments were performed on isolated perfused Sprague-Dawley (SD) rat’s hearts. Mg-Or (1 mM) was compared to Control (buffer); IPostC (ischemic postconditionning); OA (orotic acid; 1 mM) and, MgCl2 (1 mM). We also compared early (2 minutes before the onset of reperfusion) and delayed (3 minutes after reperfusion) administration of Mg-Or. Invasive left ventricular (LV) function and infarct size (IS) were measured. In vivo regional ischemia reperfusion (I/R) were performed in SD rats by coronary ligation. Mg-Or was administered at reperfusion comparing early and delayed administration regimens. All rat hearts were subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion Compared to control in the isolated rat heart model of I/R injury, administration of Mg-Or at the very onset of reperfusion was associated with significant recovery of LV function (dLVP/dt max: 60.1±2.5 vs. 38.6±3.7, p < 0.01 and dLVP/dt min: 66.4±3.2 vs. 46±4.1, p < 0.01) and IS reduction (32.1±1.8 vs. 70±3.5, p<0.01). The magnitude of protection was comparable to that observed with IPostC. OA was as efficient as Mg-Or on LV function (dLVP/dt max: 60.1±2.5 vs 57.2±5.2, p=NS and dLVP/dt min: 66.4±3.2 vs 62.5±7.4, p=NS) but induced less IS reduction (32.1±1.8 vs. 46.7±3, p<0.01). No protection was observed with MgCL2 administration. Delaying the administration of Mg-Or had a negative effect on functional recovery parameters (dLVP/dtmax 55.6±2.2 vs. 38.7±3.7, p < 0.01), yet the IS reduction were similar (35.4±1.8 vs 32.1±1.8, p=NS). In vivo experiments showed that both early and delayed administration of Mg-Or at reperfusion elicited a comparable degree of IS reduction. Our data suggest that Mg-Or, already known for its beneficial effects in human chronic myocardial diseases, may reduce infarct size and preserve LV function when administered at the onset of reperfusion following myocardial ischemia.
- © 2012 by American Heart Association, Inc.