MYOCARDIAL PROTECTION BY A CARDIOSELECTIVE FREE-RADICAL SCAVENGER

Oxygen-derived free radicals are involved in myocardial reperfusion in jury. In the present study MDL 74,405 )-3,4-dihydro-6-hydroxy-N,N,N-2, 5,7,8-heptamethyl- 2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfo nate), a hydrophilic derivative of cu-tocopherol, has been shown to in hibit lipid peroxidation in rat brain homogenate, ex vivo lipid peroxi dation in mouse heart and to accumulate in myocardial tissue. Infused i.v. MDL 74,405 induced a dose-related reduction of myocardial infarct size in pentobarbitone-anaesthetised rats subjected to 60 min coronar y artery ligation followed by 30 min reperfusion. Similarly i.v. infus ion of MDL 74,405 beginning 10 min before coronary artery occlusion (6 0 min) until 30 min after the onset of reperfusion (8 days) caused a d ecrease of infarct size associated with an increase in aortic now. Pla sma levels of creatine phosphokinase were significantly reduced. In is olated infarcted hearts, obtained from MDL 74,405-treated rats after 8 days of reperfusion and perfused according to the Langendorff techniq ue, an increase in the contractility index (+) and (-) dP/dt(max) was apparent. In isolated non-infarcted rat hearts subjected to 30 min no- flow global ischaemia, perfusion with MDL 74,405 resulted in an increa se in heart rate and the contractility indices (+) dP/dt(max) and left ventricular systolic pressure during reperfusion. In conclusion MDL 7 4,405, is a cardioselective free radical scavenger, that reduces myoca rdial infarct size and attenuates post-ischaemic dysfunction.