Protective effects of an alpha-tocopherol analogue against myocardial reperfusion injury in rats.

Free radicals may cause part of the irreversible injury which occurs during myocardial infarction and reperfusion. In the present study MDL 73404, an alpha-tocopherol analogue which is a free radical scavenger has been evaluated for its effects on infarct size in an anaesthetised rat model of coronary artery ligation (60 min) and reperfusion (30 min). Intravenous infusion of the compound began 10 min before occlusion until the end of reperfusion. MDL 73404 (0.3-3 mg/kg per h) reduced infarct size, although not in a dose-related manner. Infusion of MDL 73404 (3 mg/kg per h) commencing 30 min before reperfusion until the end of reperfusion also induced a significant reduction in infarct size. In the isolated rat heart (Langendorff technique) subjected to 30 min no-flow global ischaemia, pretreatment with MDL 73404 (0.03 and 0.1 mM) in the perfusion buffer and during 30 min of reperfusion resulted in a significant increase in the maximal pressure development (+dP/dt max) and relaxation (-dP/dt max), left ventricular systolic pressure and heart rate during reperfusion, whereas left ventricular diastolic pressure was significantly reduced. In contrast, only one control heart out of five exhibited signs of recovery. Replacement, for 2 min, with a cardioplegic solution before the 30 min period of ischemia resulted in an increased heart rate and contractility during reperfusion compared to hearts that did not receive the cardioplegic solution. The presence of MDL 73404 (0.03 and 0.1 mM) in the perfusion fluid induced an additional increase in left ventricular systolic pressure to the pre-ischaemic levels. MDL 73404 may have potential for cardioprotective use in acute reperfusion of the myocardium following ischaemia.