Prostacyclin in experimental myocardial ischemia: Effects on hemodynamics, regional myocardial blood flow, infarct size and mortality

Abstract

To determine the actions of prostacyclin in acute myocardial ischemia, the left anterior descending coronary artery was ligated in 26 anesthetized dogs. At 15 and 45 minutes after coronary ligation, regional myocardial blood flow (ml/min per 100 g) and cardiac output (ml/min) were measured by the radiolabeled microsphere technique (strontium-85 or cerium-141 18 to 10μ]). The dogs were randomly allocated 17 minutes after coronary ligation to a control group (n = 17) or to treatment with prostacyclin infusion at 0.32 μg/kg per min for 6 hours (n = 9). Heart rate and cardiac output were unchanged (p > 0.05) by prostacyclin; mean systemic arterial pressure decreased from 121 ± 8 to 90 ± 3 mm Hg (mean ± standard error of the mean) (p < 0.01) and systemic vascular resistance from 2,690 ± 339 to 2,372 ± 398 dynes · s · cm −5 (p < 0.05). Prostacyclin reduced blood flow in nonischemic myocardium from 116 ± 12 to 80 ± 3 ml/min (p < 0.01); flow in the ischemic zone was unchanged (p > 0.05) from 22 ± 5 to 20 ± 4 ml/min. Thus, the ratio of ischemic to nonischemic flow was increased by prostacyclin from 0.20 ± 0.03 to 0.25 ± 0.05 (p < 0.05); neither the ischemic nor the nonischemic endocardial/epicardial flow ratio was altered (p > 0.05). In the control dogs, all variables remained constant (p > 0.05) from 15 to 45 minutes. Mortality to 6 hours after coronary ligation was 0 of 9 in prostacyclin-treated versus 6 of 17 (35 percent) in control dogs (p < 0.06). Surviving dogs were killed 24 hours after ligation and infarct size, determined by planimetry and weight techniques, was 18 ± 2 percent of left ventricle in prostacyclin-treated dogs versus 22 ± 2 percent in control dogs (p > 0.05). Thus, prostacyclin in acute myocardial ischemia decreases myocardial oxygen demands, maintains ischemic myocardial blood flow while decreasing nonischemic flow, and greatly reduces early mortality.