Cardioprotective effects of the MR contrast agent MnDPDP and its metabolite MnPLED upon reperfusion of the ischemic porcine myocardium

Purpose: To evaluate whether manganese dipyridoxyl diphosphate (MnDPDP) or its metabolite manganese dipyridoxyl ethyldiamine (MnPLED) reduces post-ischemic myocardial injury. Material and Methods: Left anterior descending artery (LAD) in anesthetized pigs was occluded (30 min) followed by reperfusion (120 min) during hemodynamic monitoring and infarct assessment. Three mu mol/kg MnDPDP. 1 mu mol/kg MnPLED (or a mixture of both) or saline was injected i.v. 10 min before reperfusion followed by infusion of either 3 mu mol/kg/h MnDPDR 1 mu mol/kg/h MnPLED (or a mixture of both) or saline. The plasma concentrations of MnDPDR MnPLED and other metabolites (e.g., ZnDPDP and ZnPLED),A,cre analyzed. Results: Femoral blood flow was reduced by 60% during early reperfusion in controls. whereas only 23 and 31% reductions were seen in animals treated with MnDPDP and MnPLED. During that time, +LV/dP and -LV/dP (maximum rate of left ventricular isovolumic contraction and relaxation, respectively), Systolic pressure and diastolic pressure fell significantly less in animals treated with MnDPDP or MnPLED. Three out of 5 control animals experienced ventricular fibrillation (VF) during reperfusion, whereas VF was not seen in any of the pigs treated with MnPLED or/and MnDPDR The infarct sizes in saline- and MnPLED-treated animals were 39 +/-6 and 16 +/-5%, respectively, of the occluded areas. MnDPDP did not reduce the infarct size. A mixture of MnDPDP and MnPLED significantly reduced infarct size (10 +/-4%). When reperfusion started and throughout reperfusion, almost all injected MnDPDP was present as Zn-metabolites. Conclusion: MnPLED seems to reduce reperfusion-induced cardiac dysfunction and infarct size in pigs, MnDPDP does not reduce infarct size in the pig, probably because of the rapid exchange of Mn2+ for Zn2+ taking place in the pig.