Karlsson J O, Brurok H, Eriksen M, Towart R, Toft K G, Moen O, Engebretsen B, Jynge P, Refsum H
Department of Pharmacology, Linköping University, Linköping, Sweden.
Acta Radiol. 2001 Nov;42(6):540-7. doi: 10.1080/028418501127347340.
To evaluate whether manganese dipyridoxyl diphosphate (MnDPDP) or its metabolite manganese dipyridoxyl ethyldiamine (MnPLED) reduces post-ischemic myocardial injury.
Left anterior descending artery (LAD) in anesthetized pigs was occluded (30 min) followed by reperfusion (120 min) during hemodynamic monitoring and infarct assessment. Three micromol/kg MnDPDP, 1 micromol/kg MnPLED (or a mixture of both) or saline was injected i.v. 10 min before reperfusion followed by infusion of either 3 micromol/kg/h MnDPDP, 1 micromol/kg/h MnPLED (or a mixture of both) or saline. The plasma concentrations of MnDPDP, MnPLED and other metabolites (e.g., ZnDPDP and ZnPLED) were analyzed.
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 MnDPDP. 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.
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.
评估二磷酸吡哆醛锰（MnDPDP）或其代谢产物二磷酸吡哆醛乙二胺锰（MnPLED）是否能减轻缺血后心肌损伤。
在血流动力学监测和梗死评估过程中，对麻醉猪的左前降支动脉（LAD）进行阻断（30分钟），随后进行再灌注（120分钟）。在再灌注前10分钟静脉注射3微摩尔/千克MnDPDP、1微摩尔/千克MnPLED（或两者的混合物）或生理盐水，随后输注3微摩尔/千克/小时MnDPDP、1微摩尔/千克/小时MnPLED（或两者的混合物）或生理盐水。分析MnDPDP、MnPLED和其他代谢产物（如ZnDPDP和ZnPLED）的血浆浓度。
对照组在再灌注早期股动脉血流量减少60%，而用MnDPDP和MnPLED治疗的动物分别仅减少23%和31%。在此期间，用MnDPDP或MnPLED治疗的动物中，左心室压力上升最大速率（+LV/dP）和左心室压力下降最大速率（-LV/dP，分别为左心室等容收缩和舒张的最大速率）、收缩压和舒张压下降明显较少。5只对照动物中有3只在再灌注期间发生心室颤动（VF），而在用MnPLED或/和MnDPDP治疗的猪中未观察到VF。生理盐水组和MnPLED组动物的梗死面积分别为闭塞区域的39±6%和%16±5%。MnDPDP未减小梗死面积。MnDPDP和MnPLED的混合物显著减小了梗死面积（10±4%）。当再灌注开始并在整个再灌注过程中，几乎所有注射的MnDPDP都以锌代谢产物的形式存在。
MnPLED似乎能减轻猪再灌注诱导的心脏功能障碍和梗死面积。MnDPDP不能减小猪的梗死面积，可能是因为猪体内Mn2+与Zn2+快速交换。
