The effects of phospholipase A 2 inhibition on experimental infarct size, left ventricular hemodynamics and regional myocardial blood flow

Abstract

It has been reported that activation of phospholipase A 2 and the subsequent degradation of membrane phospholipids are responsible for irreversible myocardial injury. Thus, we examined whether a phospholipase A 2 inhibitor 1-(benzylmethyl-amino)-3-[(α,α,α-trifluoro-m-tolyl)oxy]-2-propanol hydrochloride, can reduce myocardial necrosis after coronary artery occlusion. In 14 anesthetized dogs, 1 minute after coronary occlusion, 99mTc-labeled albumin microspheres (8 mCi) were injected into the left atrium for future assessment of the hypoperfused zone. After 15 minutes, the dogs were randomized to a control group ( n = 7) and a treated group ( n = 7, 2 mg/kg i.v.). After 6 hours, infarct size and hypoperfused zones were measured using triphenyltetrazolium chloride staining and autoradiography, respectively. The hypoperfused zone, as a percentage of the left ventricle, was 26 ± 3% and 23 ± 1% in the control and the treated groups (NS), respectively. The percentage of the hypoperfused zone that evolved to necrosis was 98 ± 4% in the control group and 45 ± 10% in the treated group ( P < 0.001) showing a reduction of 54%. By weight, in the control group, necrosis involved 26 ± 4 g of the left ventricle while in the treated group it was 9 ± 2 g ( P < 0.005). In 6 additional dogs, left ventricular hemodynamics and regional myocardial blood flow were studied before and after treatment i.e., 15 and 30 minutes after coronary occlusion, respectively. Phospholipase A 2 inhibitor did not acutely change heart rate, aortic pressure, left ventricular end-diastolic and systolic pressures, left ventricular dP dt and regional myocardial blood flow. Thus, phospholipase A 2 inhibitor salvaged the acutely ischemic myocardium, reducing necrosis by over 50% in the canine model. It is postulated that since this effect was not related to the studied hemodynamic parameters and regional myocardial blood flow, it may be related to the preservation of membrane integrity.