Fiedler V B
J Cardiovasc Pharmacol. 1984 Mar-Apr;6(2):318-24. doi: 10.1097/00005344-198403000-00017.
The effects of oral nafazatrom pretreatment (10 mg/kg, twice a day, for 10 days) on myocardial ischemia were studied in the rabbit heart during 6-h occlusion of the left anterior descending coronary artery (LAD). The tension-time index (TTI), hemodynamics, and ischemia size were determined (Evan's blue-triphenyltetrazolium chloride staining with planimetry). In drug-vehicle controls, left ventricular (LV) and peripheral pressures and LV dP/dtmax decreased, while heart rate, end-diastolic pressure, the TTI, and electrocardiographic ST segments increased. Hemodynamics were nearly unaltered in the nafazatrom-pretreated animals, except for a heart rate elevation during the initial phase of LAD occlusion. In drug-treated hearts, 45 +/- 6% of the LAD perfusion region at risk was ischemic, showing a patchy distribution. In vehicle controls, 82 +/- 4% (p less than 0.02 vs. nafazatrom pretreatment) of the LAD-perfused myocardial regions was transmurally ischemic, showing a uniform pattern. Thus, nafazatrom pretreatment prevented most hemodynamic changes following LAD occlusion in the rabbit heart. Significant amounts of the muscle remained normoxic within the nonperfused arterial regions. These results indicate that the inhibition of lipoxygenase enzymes by nafazatrom may delay the development of ischemic damage to the heart following acute coronary artery occlusion.
研究了口服萘呋胺酯预处理（10毫克/千克，每日两次，共10天）对兔心脏在左冠状动脉前降支（LAD）闭塞6小时期间心肌缺血的影响。测定张力-时间指数（TTI）、血流动力学和缺血面积（采用伊文思蓝-氯化三苯基四氮唑染色及平面测量法）。在药物-载体对照组中，左心室（LV）和外周压力以及LV dP/dtmax降低，而心率、舒张末期压力、TTI和心电图ST段升高。在萘呋胺酯预处理的动物中，除了在LAD闭塞初始阶段心率升高外，血流动力学几乎未改变。在药物处理的心脏中，有风险的LAD灌注区域的45±6%发生缺血，呈斑片状分布。在载体对照组中，LAD灌注心肌区域的82±4%（与萘呋胺酯预处理相比，p<0.02）发生透壁性缺血，呈均匀模式。因此，萘呋胺酯预处理可预防兔心脏LAD闭塞后的大多数血流动力学变化。在未灌注的动脉区域内，大量肌肉仍保持正常氧合。这些结果表明，萘呋胺酯对脂氧合酶的抑制作用可能会延迟急性冠状动脉闭塞后心脏缺血性损伤的发展。
