Montrucchio G, Alloatti G, Mariano F, de Paulis R, Comino A, Emanuelli G, Camussi G
Clinica Medica Generale III, Ospedale S. Luigi, Gonzaga, Italy.
Am J Pathol. 1990 Jul;137(1):71-83.
This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the first minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion.
本研究表明，在再灌注前给予PAF受体拮抗剂SDZ 63.675（5mg/kg体重）可显著减轻家兔在经历40分钟冠状动脉闭塞和再灌注后的血液学和血流动力学改变，以及坏死区域的大小。用SDZ 63.675预处理可防止右心室血液中血小板计数的减少（为缺血前对照值的86.6±2.8%）以及短暂性心动过缓（85.0±2.8%）、全身性低血压（58.0±2.8%）和右心室压力升高（125.0±3.6%），这些情况在未治疗的对照家兔再灌注的最初几分钟内很明显。再灌注后2小时和24小时，用四氮唑染色判断，SDZ 63.675治疗的家兔梗死面积显著减小（对照动物在2小时和24小时时梗死面积分别为危险区域的66.0±2.9%和63.46±2.09%，而SDZ 63.675治疗的家兔在2小时和24小时时分别为危险区域的38.9±5.2%和37.11±2.44%）。再灌注24小时后对心脏组织进行组织学检查证实了这一结果。此外，SDZ 63.675显著减少了再灌注15分钟后在心脏中央缺血区域和肺部出现的111In-奥克辛标记血小板的聚集。这些结果表明，PAF在再灌注期间观察到的心肌损伤演变中起作用。
