Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor
Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor
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DOI：
10.1016/s0003-4975(01)03329-x
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发表时间：
2002-02-01
影响因子：
4.6
通讯作者：
Sellke, FW
中科院分区：
文献类型：
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作者：
Faro, R;Toyoda, Y;Sellke, FW
背景多聚腺苷三磷酸合成酶的激活在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一种新的有效的聚（ADP-核糖）合成酶抑制剂，PJ 34，是否提供心肌保护。对猪进行60分钟的局部缺血，然后进行180分钟的再灌注。在再灌注前15至5分钟静脉内施用10 mg/kg的PJ 34（PJ 34; n = 6）（治疗组），随后在再灌注前5分钟至再灌注180分钟结束时以3 mg/kg/小时的PJ 34施用。对照猪（n = 7）仅接受溶媒。监测动脉压、左心室压和冠状动脉血流。对于PJ 34和对照猪组，PJ 34分别显示出梗死面积的显著减小（37.5% +/-4.5%和50.5% +/-4.8%的风险面积）（p < 0.05）。与对照猪相比，在PJ 34中还观察到收缩后缩短的显著减少，以及节段缩短的改善，以及压力随时间的正一阶导数（+dP/dt）最大值（p < 0.05）。我们的研究结果表明，PJ 34通过减少心肌梗死面积和促进缺血后局部和整体功能恢复来提供心脏保护。(C)2002年由胸外科医师协会出版。
Background. The activation of poly (ADPribose) 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.Methods. 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.Results. 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).Conclusions. Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery. (C) 2002 by The Society of Thoracic Surgeons.