Cardioplegic effect of Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor against ischemia-reperfusion myocardial injury in cardiac surgery

缺血再灌注损伤是目前心脏外科面临的最严重的问题之一。聚腺苷5 '-二磷酸核糖合成酶（Poly（adenosine 5'-diphosphate-ribose）synthetase，PARS）抑制剂可通过抑制氧化应激引起的能量消耗而减轻缺血再灌注损伤。本研究旨在评价含PARS抑制剂3-氨基苯甲酰胺（3-AB）的心脏停搏液对心脏停搏引起的心肌缺血再灌注损伤的保护作用。心脏停搏液（St.托马斯溶液）每隔30分钟给药一次，停搏90分钟，然后再灌注20分钟。3-AB（-）组（n=8）用标准心脏停搏液和终末温停搏液灌注大鼠心脏，而3-AB（+）组（n=8）接受补充有3-AB（100 μ M）的这些溶液。监测停搏前后左室功能和心肌酶的释放。再灌注后，NAD+在再灌注过程中，3-AB（+）组的氧化应激和细胞凋亡水平显著高于对照组。（P=0.005）dp/dt和较低的肌酸磷酸激酶（CPK）和葡萄糖胺-草酰乙酸转氨酶（GOT）水平（CPK ; P=0.003 GOT ; P<0.001）3-AB（+）组心肌细胞内NAD+水平也较对照组高（P<0.001）。氧化应激的免疫组化研究显示，3-AB（+）组细胞核染色程度较轻（P=0.007），细胞凋亡比例较低。

Ischemic-reperfusion injury has been one of the most serious problem even in current cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury by preventing energy depletion associated with oxidative stress. The purpose of our study was to evaluate the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest.Isolated rat hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution (St.Thomas solution) given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n=8) were perfused with a standard cardioplegic solution and terminal warm cardioplegia, whereas the 3-AB(+) group (n=8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis.During reperfusion, the 3-AB(+) group showed significantly higher (P=0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK ; P=0.003 GOT ; P<0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P<0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P=0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group.In conclusion, cardioplegic solution supplemented with PARS inhibitor provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress.