Demonstration of Lateral and Epicardial Border Zone Salvage by Flurbiprofen Using an In Vivo Method for Assessing Myocardium at Risk
Demonstration of Lateral and Epicardial Border Zone Salvage by Flurbiprofen Using an In Vivo Method for Assessing Myocardium at Risk
复制标题
使用体内方法评估处于危险中的心肌，演示氟比洛芬对外侧和心外膜边界区的挽救作用
作者：
J. R. Darsee;R. Kloner;E. Braunwald
本研究的目的是：(1)建立一种测定实验性冠状动脉闭塞后处于危险中的心肌的体内方法；(2)确定可抢救缺血边界带的空间几何形状；(3)评价抗炎药氟比洛芬对缺血心肌的保护作用。22只开胸犬接受左冠状动脉前降支闭塞术，随机分为治疗组（氟比洛芬1 mg/kg，闭塞后30分钟和4小时静脉注射）和对照组（生理盐水组，n = 11）。阻断后6小时左心房注射亚甲基蓝3 mI/kg，立即取心，横向切开。对未被亚甲基蓝灌注的区域（危险区域[Ar]）进行追踪、测量，并与三苯四氮氯化铵孵育后的坏死区域（An）进行比较。两组Ar值相近（对照组28.2±2.6%；治疗组25.2±2.3%；NS）。对照犬的An/Ar为96.2±0.7%，心外膜和心内膜的An/Ar值相近。在治疗犬中，An/Ar为66.9±8.9% (p < 0.001)，心外膜抢救多于心内膜抢救。An在Ar上的地形叠加显示，抢救发生在心外膜和梗死的外侧。我们得出的结论是：(1)体内亚甲基蓝法评估处于危险状态的心肌有助于标准化实验梗死面积；(2)氟比洛芬在闭塞后30分钟和4小时使用，是缩小梗死面积的有效药物；(3)氟比洛芬治疗犬心肌在梗死的外侧和心外膜边界均有挽救。
SUMMARY The purposes of this investigation were (1) to develop an in vivo method of determining the myocardium at risk after experimental coronary occlusion; (2) to define the spatial geometry of the salvageable ischemic border zone; and (3) to assess the ability of flurbiprofen, an antiinflammatory agent, to protect ischemic myocardium from necrosis. Twenty-two open-chest dogs underwent left anterior descending coronary artery occlusion and were randomized to treated (flurbiprofen 1 mg/kg i.v. at 30 minutes and 4 hours after occlusion; n = 11) or control (saline; n = 11) groups. Six hours after occlusion, methylene blue, 3 mI/kg, was injected into the left atrium, and immediately thereafter the hearts were removed and sliced transversely. Areas not perfused by methylene blue (area at risk [Ar]) were traced, planimetered, and compared to the area of necrosis (An) after incubation in triphenyltetrazolium chloride. The Ar for the two groups were similar (control 28.2 ± 2.6%; treated 25.2 ± 2.3% of total left ventricle; NS). In control dogs, An/Ar was 96.2 ± 0.7%, with similar values for the epicardium and endocardium. In treated dogs, An/Ar was 66.9 ± 8.9% (p < 0.001), with greater epicardial than endocardial salvage. Topographic superimposition of the An on the Ar showed that salvage occurred both on the epicardial and lateral aspects of the infarct. We conclude that (1) the in vivo methylene blue method of assessing myocardium at risk is useful in standardizing experimental infarct size; (2) flurbiprofen, administered 30 minutes and 4 hours after occlusion, is a potent agent for reducing infarct size; and (3) salvage of myocardium occurs both at the lateral and epicardial borders of the infarct in dogs treated with flurbiprofen.