Evolution of free radical formation during low-flow ischemia and reperfusion in isolated rat heart

Abstract

Free radicals have been implicated in several aspects of cellular injury, both during ischemia and reperfusion of the myocardium. In this study, formation of free radicals in the isolated rat heart was measured a) directly using electron paramagnetic resonance (EPR) spectroscopy and b) indirectly using the generation of thiobarbituric acid reactants as an index of lipid peroxidation. EPR spectra of frozen heart powder recorded at 100 degrees K show several lines and consist of different components separated by temperature studies: signal C disappears after warming the sample 1 minute at 190 degrees K and is suggestive of a triplet signal g = 2.001, aN = 25 Gauss; signal B g parallel = 2.034, g perpendicular = 2.007, disappears after 1 min at 240 degrees K, and is similar to those previously reported for oxygen alkylperoxyl free radical; the remaining signal, signal A with g = 2.004 is identical to that of a carbon-centered ubiquinone free radical. The total free radical concentration in isolated rat heart perfused at a constant flow rate of 12 ml/min was increased by 44% compared with control (p less than 0.05) after 10 minutes of normothermic global ischemia with a 10% residual flow, and by only 31% compared with control after 20 seconds of reflow with oxygenated perfusate (p less than 0.05). Compared with the reperfused group, trimetazidine 10(-5) M administered 15 minutes before the ischemic period decreased the free radical concentration (-20%). However, this free radical generation in heart was not associated with a concomitant increase of lipid peroxides.

Protective effect of trimetazidine on myocardial mitochondrial function in an ex-vivo model of global myocardial ischemia

“…This enzyme-based mechanism could explain the antioxidant properties of trimetazidine already described by Maupoil et al (1990). The confirmation of our findings in future studies may make it possible to explain the molecular mechanisms involved in that antioxidant effect (until now mainly regarded as a mere consequence of the trimetazidine-induced bmetabolic shiftQ) (Kantor et al, 2000) and to fully explain the anti-ischemic effect of trimetazidine, as these new data clearly demonstrate that it goes far beyond the bmetabolic shiftQ (being also present in an experimental model in which the hearts were not exposed to free fatty acids).…”

“…This raises the hypothesis that trimetazidine acts on heart mitochondria, thus allowing a better use of the limited amount of O 2 available during ischemia, by mechanisms not yet fully understood, but which may involve a preferential use of glucose and/or a decrease in reactive oxygen species production (Maupoil et al, 1990). In ischemic hearts perfused with free fatty acids and trimetazidine, ATP levels have been shown to be preserved by some authors (Fantini et al, 1994) and decreased by others (Demaison et al, 1995).…”

Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion

“…A detectable burst of ROS is generated early in reperfusion (4,16,71,96,97,112). Early research led to the belief that during cardiac ischemia, oxygen content would rapidly decrease to complete anoxia, with all oxygen consumed by cytochrome oxidase.…”

The first histopathological evidence of trimetazidine for the prevention of contrast-induced nephropathy

“…26,27 TMZ was shown to have antioxidant properties. 28,29 Under ischemic conditions TMZ reduces the loss of intracellular K + induced by oxygen free radicals and protects cellular membrane. 30 It was shown that the plasma MDA level decreased in response to pretreatment with TMZ before coronary artery bypass surgery.…”