Smalling R W, Feld S, Ramanna N, Amirian J, Felli P, Vaughn W K, Swenson C, Janoff A
Division of Cardiology, University of Texas Health Science Center, Houston, USA.
Circulation. 1995 Aug 15;92(4):935-43. doi: 10.1161/01.cir.92.4.935.
Prostaglandin E1 (PGE1) inhibits leukocyte and platelet function and reduces infarct size during left atrial infusion. Intravenous liposomal PGE1 (TLC C-53) accelerates thrombolysis and prevents reocclusion in canine coronary thrombosis. We tested the hypothesis that intravenous TLC C-53 would attenuate reperfusion injury in a canine infarction-reperfusion model.
Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE1 (2 micrograms/kg), or TLC C-53 (2 micrograms/kg PGE1) after 2 hours of left anterior descending (LAD) occlusion just before reperfusion. Hemodynamic assessment, regional myocardial blood flow determination with radioactive microspheres, myocardial leukocyte infiltration by myeloperoxidase assay, and estimation of infarct size using triphenyl tetrazolium chloride staining were performed. Regional fractional shortening was measured with sonomicrometer crystals implanted in the midmyocardium. Infarct size as a percentage of the risk region was significantly reduced (P < .05) with TLC C-53 (37.9 +/- 17.4%) compared with PGE1 (56.7 +/- 13.9%) or placebo (58.0 +/- 9.9%) infusion. Infarct salvage with TLC C-53 was independent of collateral blood flow by ANCOVA. There was a dramatic reduction in myeloperoxidase activity in the infarct, risk, and border regions of dogs treated with TLC C-53 compared with placebo. Enzyme activity was also significantly reduced (P < .05) in the infarct zone with TLC C-53 (0.11 +/- 0.1 U/100 mg) treatment compared with PGE1 (0.38 +/- 0.3 U/100 mg). No significant differences in regional myocardial blood flow or myocardial function among treatment groups were identified, although there was a trend toward improved function in the TLC C-53 dogs.
Bolus intravenous administration of TLC C-53 immediately before reperfusion results in reduced leukocyte infiltration and substantial infarct salvage. TLC C-53 mah be useful in limiting reperfusion injury during treatment of acute myocardial infarction.
前列腺素E1（PGE1）可抑制白细胞和血小板功能，并在左心房输注期间减小梗死面积。静脉注射脂质体PGE1（TLC C-53）可加速犬冠状动脉血栓形成的溶栓过程并防止再闭塞。我们检验了静脉注射TLC C-53可减轻犬梗死-再灌注模型中再灌注损伤这一假设。
21只开胸犬在左前降支（LAD）闭塞2小时后随机接受10分钟的静脉输注，在再灌注前分别输注脂质体稀释剂（安慰剂）、游离PGE1（2微克/千克）或TLC C-53（2微克/千克PGE1）。进行血流动力学评估、用放射性微球测定局部心肌血流量、通过髓过氧化物酶测定法评估心肌白细胞浸润情况以及使用氯化三苯基四氮唑染色法估计梗死面积。使用植入心肌中层的声纳晶体测量局部缩短分数。与输注PGE1（56.7±13.9%）或安慰剂（58.0±9.9%）相比，TLC C-53组（37.9±17.4%）梗死面积占危险区域的百分比显著降低（P<0.05）。通过协方差分析，TLC C-53的梗死挽救与侧支血流无关。与安慰剂相比，接受TLC C-53治疗的犬梗死、危险和边缘区域的髓过氧化物酶活性显著降低。与PGE1（0.38±0.3单位/100毫克）治疗相比，TLC C-53（0.11±0.1单位/100毫克）治疗的梗死区域酶活性也显著降低（P<0.05）。尽管TLC C-53组犬的功能有改善趋势，但各治疗组之间局部心肌血流量或心肌功能无显著差异。
在再灌注前立即静脉推注TLC C-53可减少白细胞浸润并显著挽救梗死心肌。TLC C-53可能有助于在急性心肌梗死治疗期间限制再灌注损伤。
