Faro Renato, Toyoda Yoshiya, McCully James D, Jagtap Prakash, Szabo Eva, Virag Laszlo, Bianchi Cesario, Levitsky Sidney, Szabo Csaba, Sellke Frank W
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Ann Thorac Surg. 2002 Feb;73(2):575-81. doi: 10.1016/s0003-4975(01)03329-x.
The activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection.
Pigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored.
The PJ34 showed significant reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05).
Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.
聚（ADP - 核糖）合成酶的激活在导致心肌缺血 - 再灌注损伤的发病机制中起重要作用。本研究的目的是确定新型强效聚（ADP - 核糖）合成酶抑制剂PJ34是否能提供心肌保护作用。
对猪进行60分钟的局部缺血，随后进行180分钟的再灌注。在再灌注前15分钟至5分钟静脉注射10mg/kg的PJ34（PJ34组；n = 6），然后在再灌注前5分钟至再灌注180分钟结束时以3mg/kg/小时的剂量静脉注射PJ34。对照猪（n = 7）仅接受赋形剂。监测动脉压、左心室压力和冠状动脉血流量。
PJ34组和对照组猪的梗死面积分别显著减小（分别为危险区域面积的37.5%±4.5%和50.5%±4.8%）（p < 0.05）。与对照猪相比，PJ34组还观察到收缩后缩短显著减少，节段缩短改善，以及压力随时间的一阶导数最大值（+dP/dt）增加（p < 0.05）。
我们的结果表明，PJ34通过减小心肌梗死面积和增强缺血后局部和整体功能恢复来提供心脏保护作用。
