REDUCTION OF EXPERIMENTAL MYOCARDIAL INFARCT SIZE BY CORTICOSTEROID ADMINISTRATION
REDUCTION OF EXPERIMENTAL MYOCARDIAL INFARCT SIZE BY CORTICOSTEROID ADMINISTRATION
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DOI：
10.1172/jci107221
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发表时间：
1973-01-01
影响因子：
15.9
通讯作者：
BRAUNWALD, E
中科院分区：
文献类型：
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作者：
LIBBY, P;MAROKO, PR;BRAUNWALD, E
在28只狗中研究了药理学剂量的氢化可的松对急性心肌缺血性损伤的范围和严重程度以及对急性冠状动脉闭塞后随后的坏死的影响。为了研究急性心肌损伤，在左心室前表面10 ~ 15个部位重复记录心外膜心电图。在冠状动脉闭塞后30和60 min分别分析平均ST段抬高（ST段抬高）和ST段抬高超过2 mV的部位数（NST），这是心肌损伤的幅度和范围的指标。对照组在此时间段内，S_（10）T_（10）和NST无明显变化，而治疗组在记录30 min后立即给予50 mg/kg氢化可的松，S_（10）T_（10）从3.5±0.8 mV降至1.1±0.4 mV（P<0.01），NST从6.7±1.1降至1.4±0.8（P<0.01）。为了研究氢化可的松对坏死的影响，将冠状动脉闭塞后15分钟的心外膜ST段抬高与心肌肌酸磷酸激酶活性（CPK）和24小时后每个部位的组织学表现进行比较。在对照组（14只狗）中，建立了15分钟时ST段抬高（单位：毫伏）与24小时后CPK活性（单位：国际单位/毫克蛋白质）之间的关系：log CPK = -0.0611ST +1.26（N= 102个样本，r= -0.79）。在处理组中，氢化可的松（50 mg/kg i. v.）在闭塞后30 min（7只狗）或闭塞后6 h（6只狗）给予。两组均在闭塞后12 h接受补充剂量的氢化可的松（25 mg/kg）。两个给药组显示的CPK抑制低于每个部位ST段抬高的预期值，回归线的斜率显著较低：半小时组和6小时组分别为log CPK = -0.0288ST +1.26（N= 48，r= -0.71）和log CPK = -0.0321ST +1.31（N= 48，r= -0.76）。组织学上，闭塞后15 min ST段抬高小于2 mV的部位24 h后表现正常。对照组中ST段抬高（> 2 mV）的部位在96%的样本中显示出与早期心肌梗死相符的组织学变化，而在治疗组中，这分别仅发生在61%和63%的样本中，表明超过三分之一的部位由于氢化可的松的介入治疗而免于发生坏死。因此，即使在冠状动脉闭塞后6小时开始给药，药理剂量的氢化可的松也能防止心肌细胞进展为缺血性坏死。图片
The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (S̄T̄) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group S̄T̄ and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, S̄T̄ fell from 3.5±0.8 to 1.1±0.4 mV (P<0.01) and NST was reduced from 6.7±1.1 to 1.4±0.8 (P<0.01). In order to study the influence of hydrocortisone on necrosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N= 102 specimens,r= -0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs). Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK = -0.0288ST + 1.26 (N= 48,r= -0.71) and log CPK = -0.0321ST + 1.31 (N= 48,r= -0.76) in the ½ h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion.Images