Shea M J, Murtagh J J, Jolly S R, Abrams G D, Pitt B, Lucchesi B R
Eur J Pharmacol. 1984 Jun 15;102(1):63-70. doi: 10.1016/0014-2999(84)90338-8.
The effect of nafazatrom, a new antithrombotic agent, was studied in a canine model of regional myocardial ischemia. Nafazatrom was administered 1 mg/kg intravenously every 6 h for 48 h. After 24 h of drug or placebo administration, animals underwent 90 min of occlusion of the proximal left circumflex coronary artery followed by gradual reperfusion over a period of 30 min. Twenty-four hours later, the animals were sacrificed and infarct size was determined by histochemical staining with triphenyltetrazolium chloride. Nafazatrom-treated animals had a significant reduction in infarct size expressed as a percent of the anatomical area at risk for infarction: 21 +/- 5% in the treated group vs. 41 +/- 5% in the control group (X +/- S.E.M., P less than 0.05). Histological examination confirmed the gross results of postmortem histochemical staining. Salvage of ischemically jeopardized tissue appeared to be unrelated to myocardial oxygen demand as there were no hemodynamic differences between groups. The beneficial effects of nafazatrom are presumably related to a limitation of autolytic processes on the heart during and after ischemia as a result of the drug's ability to inhibit lipoxygenase and to prevent the enzymatic degradation of prostacyclin.
在犬局部心肌缺血模型中研究了新型抗血栓形成剂萘呋胺酯的作用。萘呋胺酯以1mg/kg静脉注射，每6小时1次，共48小时。给药24小时或给予安慰剂后，动物接受左回旋支冠状动脉近端闭塞90分钟，随后在30分钟内逐渐再灌注。24小时后，处死动物，用氯化三苯基四氮唑组织化学染色法测定梗死面积。以梗死面积占梗死危险解剖区域的百分比表示，萘呋胺酯治疗组动物梗死面积显著减小：治疗组为21±5%，对照组为41±5%（X±标准误，P＜0.05）。组织学检查证实了死后组织化学染色的大体结果。由于两组间无血流动力学差异，缺血濒危组织的挽救似乎与心肌需氧量无关。萘呋胺酯的有益作用可能与该药抑制脂氧合酶及防止前列环素酶促降解的能力有关，从而限制了缺血期间及缺血后心脏的自溶过程。
