Limitation of experimental infarct size by an angiotensin-converting enzyme inhibitor.

Abstract

The effects of angiotensin-converting enzyme inhibitor (CEI) SQ14225 [captopril] on infarct size and regional myocardial blood flow were studied in 21 anesthetized dogs subjected to 6 h of coronary occlusion. An area of myocardium at risk of necrosis was determined in vivo after 15 min of coronary occlusion but before CEI treatment (AR1) using an autoradiographic technique and after treatment after 6 h of coronary occlusion (AR2) using a fluorescent dye technique. An in vitro area at risk (AR3), which measures coronary bed size, was determined by injecting Monastral dye postmortem. Infarct size was determined by planimetry of unstained myocardium after incubating heart slices in triphenyltetrazolium chloride. Regional myocardial blood flow (RMBF) was measured by injecting tracer microspheres simultaneously with measurements of AR1 and AR2. In 11 saline-treated control dogs (group A), infarct size averaged 93 .+-. 8% of AR1, 96 .+-. 2% of AR2 and 75 .+-. 6% of AR3, respectively. In 10 dogs treated with CEI (0.25 mg/kg per h) between 30 min and 6 h after coronary occlusion (group B), infarct size was smaller and averaged 68 .+-. 5% of AR1 (P < 0.01), 79 .+-. 5% of AR2 (P < 0.005) and 57 .+-. 7% of AR3 (P < 0.05). RMBF in the ischemic zone remained constant in group A but increased by 62 .+-. 26% in group B (P < 0.025). In group B, mean arterial pressure decreased from 115 .+-. 6 to 103 .+-. 7 mmHg (P < 0.025) between 30 min and 6 h after coronary occlusion, and left atrial pressure decreased from 9.0 .+-. 1.8 to 5.7 .+-. 0.8 mmHg (P < 0.0025). These measurements did not change in group A. CEI is potent in reducing infarct size in the dog after coronary occlusion. It may act by increasing collateral flow to the ischemic zone and reducing afterload.