Brown E J, Kloner R A, Schoen F J, Hammerman H, Hale S, Braunwald E
Am J Cardiol. 1983 Mar 1;51(5):877-83. doi: 10.1016/s0002-9149(83)80148-9.
Although much attention has been directed toward interventions which reduce myocardial infarct size, the effect of such agents on the healing phase of myocardial infarction is not well understood. The present study examines the effect of the nonsteroidal anti-inflammatory agent ibuprofen, previously demonstrated to be able to reduce infarct size, and of aspirin on the healing of experimentally produced myocardial infarcts. Thirty-nine anesthetized, open-chest dogs were subjected to proximal left anterior descending coronary artery occlusions for 6 weeks. Four groups of dogs were studied: (1) a control (untreated) group: (2) ibuprofen, 12.5 mg/kg intravenously 15 minutes and 6, 12, 18, and 24 hours after occlusion (high dose); (3) ibuprofen, 12.5 mg/kg intravenously 15 minutes and 3 hours after occlusion (low dose); (4) aspirin, 30 mg/kg intravenously 15 minutes and 3 hours after occlusion. The average thickness of the transmural scar and of the noninfarcted left ventricular wall was determined from multiple measurements of formalin-fixed left ventricular slices. The ratio of transmural scar to noninfarcted wall thickness was determined. In control animals the ratio was 0.87 with only 1 of 15 animals having a ratio less than 0.60. High-dose ibuprofen-treated animals had an average ratio of 0.59 (difference not significant [NS] compared with control values), with 6 of 9 animals having a ratio less than 0.60 (p less than 0.02 compared with control values). Low-dose ibuprofen-treated animals had an average ratio of 0.66 (p less than 0.05 compared with control values), with 4 of 8 animals having a ratio less than 0.60 (p = NS compared with control values). In the aspirin-treated animals, the ratio was 0.88 (p = NS compared with control values), with 0 of 7 animals having a ratio less than 0.60 (p = NS compared with control values). Although 1 of 22 animals had ratios less than 0.60 in the control and aspirin groups, 10 of 17 had ratios less than 0.60 in the ibuprofen-treated groups (p less than 0.001). Scars in treated animals did not differ from those in control animals histologically or by analysis of hydroxyproline content per unit weight. Thus, ibuprofen, a nonsteroidal anti-inflammatory agent which reduces infarct size, is shown to increase the incidence of scar thinning after myocardial infarction.
尽管人们对减少心肌梗死面积的干预措施给予了很多关注，但此类药物对心肌梗死愈合阶段的影响尚不清楚。本研究考察了非甾体抗炎药布洛芬（先前已证明其能够减小梗死面积）和阿司匹林对实验性心肌梗死愈合的影响。39只麻醉开胸犬接受左冠状动脉前降支近端闭塞6周。研究了四组犬：（1）对照组（未治疗）；（2）布洛芬组，闭塞后15分钟及6、12、18和24小时静脉注射12.5mg/kg（高剂量）；（3）布洛芬组，闭塞后15分钟及3小时静脉注射12.5mg/kg（低剂量）；（4）阿司匹林组，闭塞后15分钟及3小时静脉注射30mg/kg。通过对福尔马林固定的左心室切片进行多次测量，确定透壁瘢痕和未梗死左心室壁的平均厚度。计算透壁瘢痕与未梗死壁厚度的比值。在对照动物中，该比值为0.87，15只动物中只有1只比值小于0.60。高剂量布洛芬治疗的动物平均比值为0.59（与对照值相比差异无统计学意义[NS]），9只动物中有6只比值小于0.60（与对照值相比p<0.02）。低剂量布洛芬治疗的动物平均比值为0.66（与对照值相比p<0.05），8只动物中有4只比值小于0.60（与对照值相比p = NS）。阿司匹林治疗的动物比值为0.88（与对照值相比p = NS），7只动物中无比值小于0.60者（与对照值相比p = NS）。尽管对照组和阿司匹林组22只动物中有1只比值小于0.60，但布洛芬治疗组17只动物中有10只比值小于0.60（p<0.001）。治疗动物的瘢痕在组织学上或单位重量羟脯氨酸含量分析方面与对照动物无差异。因此，已表明能减小梗死面积的非甾体抗炎药布洛芬可增加心肌梗死后瘢痕变薄的发生率。
