Protection of infarcted, chronically reperfused hearts by an α-tocopherol analogue

Abstract Free radicals may cause part of the irreversible injury which occurs during myocardial infarction and reperfusion. In the present study MDL 73404, a hydrophilic, cardioselective, free radical scavenger analogue of α-tocopherol, was evaluated for its effects on infract size as well as on indicators of reperfusion injury. A pentobarbitone-anaesthetised rat model of coronary artery ligation (60 min; followed by 8 days of reperfusion) was used. Intravenous infusion of MDL 73404 (3 mg/kg per h) began 10 min before occlusion until 30 min after the onset of reperfusion. MDL 73404 reduced (P dP / dt max , left ventricular systolic pressure and coronary flow after MDL 73404 compared to saline-treated controls. Infusion of [ 14 C]MDL 73404, during the time of occlusion resulted in a concentration of 14.5 ± 2.2 mg eq/g in the non-ischaemic ventricular tissue and a concentration of 3.0 ± 0.4 mg eq/g in the area at risk. After infusion for the 30 min of reperfusion, 6.4 ± 0.2 mg eq/g was detected in the non-ischaemic ventricular tissue but only 3.1 ± 0.5 mg eq/g in the area at risk. The present findings indicate that post-ischaemic dysfunction can be markedly attenuated by MDL 73404, as assessed after 8 days of reperfusion.