Efficacy of platelet depletion in counteracting the detrimental effect of acute hypercholesterolemia on infarct size and the no-reflow phenomenon in rabbits undergoing coronary artery occlusion-reperfusion

Abstract

It has recently been demonstrated that acute hypercholesterolemia per se, independently of its atherogenic effect, increases the extent of myocardial injury in rabbits undergoing coronary artery occlusion-reperfusion. Estimation of myocardial blood flow after reperfusion indicated that this deleterious effect was due to a vascular obstruction that limited the efficacy of reperfusion. The goal of this study was to evaluate the role played by platelets in contributing to the occurrence of this deleterious effect. Accordingly, New Zealand White rabbits were fed a standard laboratory chow diet (plasma cholesterol 67 +/- 12 mg/dl) or a 2% cholesterol-enriched diet for 3 days (plasma cholesterol 329 +/- 70 mg/dl). In a first series of experiments autologous platelets were labeled with 111In-oxine. After labeling, platelets were reinjected in the same animal and 30 min later coronary artery occlusion (CAO) was induced. CAO was maintained for 30 min followed by 5.5 hr of reperfusion. The animals were then killed, their hearts were excised, and each left ventricle was divided into ischemic and normally perfused samples. Myocardial samples were then counted in a gamma counter. Platelet accumulation ratio, i.e., 111In activity in the ischemic myocardium per gram of tissue divided by 111In activity in the normal myocardium per gram of tissue, was calculated. The ratio was 2.4 +/- 0.2 (mean +/- SEM) in controls (n = 7) and 10.3 +/- 1.0 in the cholesterol-fed group (n = 6, p less than .001), indicating that a marked accumulation of platelets occurs in the ischemic myocardium of hypercholesterolemic rabbits. To evaluate the importance of this phenomenon, another series of experiments was performed.(ABSTRACT TRUNCATED AT 250 WORDS)