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

European Journal of Pharmacology
L LukovicW De Jong

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 alpha-tocopherol, was evaluated for its effects on infarct 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 < 0.02) the elevated serum levels of thiobarbituric acid reactive substances and plasma levels of creatine phosphokinase (P < 0.01). An increase in cardiac output and heart rate together with a decrease (P < 0.01) in infarct size was evident in rats that had received MDL 73404, 8 days previously. Isolated infarcted hearts obtained from rats after 8 days of reperfusion had greater (P < 0.01) + dP/dt max, -dP/dt max, left ventricular systolic pressure and coronary flow after MDL 73404 compared to saline-treated controls. Infusion of [14C]MDL 73404, during the time of occlusion resulted in a concentration of 14.5 +/- 2.2 mg eq/g in the non-ischaem...Continue Reading

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Citations

Apr 1, 1994·European Journal of Pharmacology·M A PettyW De Jong
Dec 14, 2002·The International Journal of Biochemistry & Cell Biology·Estrella Núñez-DelicadoAlvaro Sánchez-Ferrer
Aug 1, 1996·Clinical and Experimental Pharmacology & Physiology·C Y HongS K Tsai
Apr 1, 1997·Journal of Cardiovascular Pharmacology·R ForratR Ferrera
Jan 1, 1995·Clinical and Experimental Pharmacology & Physiology. Supplement·W de JongM A Petty
Oct 19, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Arnaldo PinelliRoberto Accinni
Oct 16, 2010·Journal of Cardiothoracic and Vascular Anesthesia·Thorsten M SmulFranz Kehl

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