Knabb R M, Rosamond T L, Fox K A, Sobel B E, Bergmann S R
J Am Coll Cardiol. 1986 Oct;8(4):861-71. doi: 10.1016/s0735-1097(86)80428-4.
Concomitant use of pharmacologic agents may be required for maximal salvage of ischemic myocardium by reperfusion. Accordingly, in dogs with induced thrombotic coronary occlusion, the effects of intravenous diltiazem given 30 minutes before administration of streptokinase on myocardial blood flow and myocardial salvage were evaluated. Two independent types of end points were employed. Positron emission tomography was utilized for noninvasive assessment of myocardial perfusion and infarct extent. Direct measurements included quantification of myocardial infarction by assay of creatine kinase activity in myocardial homogenates. Infarct extent averaged 27.9 +/- 11.4% of left ventricular weight in 10 control dogs in which coronary occlusion was maintained for 24 hours. In eight dogs given streptokinase alone, the infarct extent averaged 16.7 +/- 10.0% of left ventricular mass (p less than 0.05 versus control). In nine other dogs given diltiazem (15 micrograms/kg per min continuously until death was induced) beginning 30 minutes before streptokinase, infarct extent averaged 9.4 +/- 6.7% of left ventricular mass (p less than 0.05 compared with reperfusion alone). At the dose administered, diltiazem did not alter blood flow, heart rate or mean arterial pressure after coronary occlusion or thrombolysis. The region at risk, determined in 16 dogs from perfusion images obtained with positron tomography and oxygen-15-labeled water after coronary occlusion, was similar in the three groups (30.6 +/- 7.3% of the left ventricle in six control dogs, 31.8 +/- 4.5% in five dogs with reperfusion alone and 30.5 +/- 11.6% in five dogs with reperfusion plus diltiazem). Infarct size quantified in terms of the extent of myocardium exhibiting less than 50% of peak carbon-11-labeled palmitate uptake 24 hours after occlusion and expressed as the percent of the region at risk averaged 89.6 +/- 11.4% in control dogs, was significantly reduced to 45.1 +/- 29.8% in dogs with reperfusion alone and was reduced further to 22.3 +/- 16.4% in dogs given diltiazem and reperfusion. Thus, concomitant treatment with diltiazem markedly enhances salvage of reperfused myocardium after coronary thrombolysis.
为了通过再灌注最大程度地挽救缺血心肌，可能需要联合使用药物。因此，在诱导血栓形成性冠状动脉闭塞的犬中，评估了在给予链激酶前30分钟静脉注射地尔硫䓬对心肌血流和心肌挽救的影响。采用了两种独立类型的终点指标。正电子发射断层扫描用于无创评估心肌灌注和梗死范围。直接测量包括通过测定心肌匀浆中的肌酸激酶活性来定量心肌梗死。在10只冠状动脉闭塞维持24小时的对照犬中，梗死范围平均为左心室重量的27.9±11.4%。在8只单独给予链激酶的犬中，梗死范围平均为左心室质量的16.7±10.0%（与对照组相比，p<0.05）。在另外9只在链激酶前30分钟开始给予地尔硫䓬（15微克/千克每分钟持续至诱导死亡）的犬中，梗死范围平均为左心室质量的9.4±6.7%（与单独再灌注相比，p<0.05）。在所给予的剂量下，地尔硫䓬在冠状动脉闭塞或溶栓后未改变血流、心率或平均动脉压。在16只犬中，通过冠状动脉闭塞后用正电子断层扫描和氧-15标记水获得的灌注图像确定的危险区域，三组相似（6只对照犬中为左心室的30.6±7.3%，5只单独再灌注犬中为31.8±4.5%，5只再灌注加地尔硫䓬犬中为30.5±11.6%）。以闭塞后24小时显示碳-11标记棕榈酸摄取峰值低于50%的心肌范围定量的梗死面积，并表示为危险区域的百分比，在对照犬中平均为89.6±11.4%，在单独再灌注犬中显著降低至45.1±29.8%，在给予地尔硫䓬和再灌注的犬中进一步降低至22.3±16.4%。因此，地尔硫䓬联合治疗显著增强了冠状动脉溶栓后再灌注心肌的挽救。
