Bednar M, Smith B, Pinto A, Mullane K M
Circ Res. 1985 Jul;57(1):131-41. doi: 10.1161/01.res.57.1.131.
The effects of nafazatrom on leukocyte function in vitro and in vivo were related to its ability to salvage ischemic myocardium in an occlusion-reperfusion model of myocardial injury in the anesthetized dog. Nafazatrom (0.4-75 microM) produced dose-related inhibition in vitro of neutrophil aggregation, superoxide anion generation, arachidonic acid metabolism, and, to a lesser extent, the release of beta-glucuronidase. In contrast, nafazatrom (0.4-37.5 microM) did not substantially influence platelet aggregation or the platelet metabolism of arachidonic acid. In vivo nafazatrom (10 mg/kg, po) reduced infarct size from 58 +/- 3% of the risk area (mean +/- SEM, n = 9) in control dogs to 23 +/- 2% of the risk area (n = 9, P less than 0.01). Nafazatrom also reduced the incidence of accompanying arrhythmias. Nafazatrom-induced myocardial salvage was not associated with any hemodynamic changes; moreover, it was independent of platelets, since thrombocytopenia did not prevent nafazatrom from exerting a protective effect. Measurements of the neutrophil-specific myeloperoxidase enzyme in ischemic myocardium indicate that the smaller infarct size in dogs treated with nafazatrom is accompanied by diminished leukocyte infiltration. Thus, the ability of nafazatrom to inhibit neutrophil function in vitro and cell infiltration in vivo may underly its myocardial-protective effects.
萘呋胺酯对体外和体内白细胞功能的影响，与其在麻醉犬心肌损伤的闭塞-再灌注模型中挽救缺血心肌的能力有关。萘呋胺酯（0.4 - 75微摩尔）在体外可产生剂量相关的中性粒细胞聚集抑制、超氧阴离子生成抑制、花生四烯酸代谢抑制，以及在较小程度上的β-葡萄糖醛酸酶释放抑制。相比之下，萘呋胺酯（0.4 - 37.5微摩尔）对血小板聚集或花生四烯酸的血小板代谢没有实质性影响。在体内，萘呋胺酯（10毫克/千克，口服）使梗死面积从对照犬风险区域的58±3%（平均值±标准误，n = 9）降至风险区域的23±2%（n = 9，P < 0.01）。萘呋胺酯还降低了伴随心律失常的发生率。萘呋胺酯诱导的心肌挽救与任何血流动力学变化无关；此外，它不依赖于血小板，因为血小板减少症并不能阻止萘呋胺酯发挥保护作用。对缺血心肌中中性粒细胞特异性髓过氧化物酶的测量表明，用萘呋胺酯治疗的犬梗死面积较小伴随着白细胞浸润减少。因此，萘呋胺酯在体外抑制中性粒细胞功能和在体内抑制细胞浸润的能力可能是其心肌保护作用的基础。
