monodehydroascorbate and Reperfusion-Injury

Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.

Topics: Animals; Antioxidants; Ascorbic Acid; Asphyxia; Brain; Dehydroascorbic Acid; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Glucose; Glutathione Peroxidase; Lactic Acid; Lectins; Oxygen; Pregnancy; Pregnancy, Animal; Reactive Oxygen Species; Regression Analysis; Reperfusion Injury; Risk; Sheep; Superoxide Dismutase; Time Factors

We investigated the influence of deep hypothermia (4 degrees C) during ischemia-reperfusion in the isolated rat heart model.. Isolated, perfused rat hearts underwent either 30 minutes of normothermic ischemia (control group) or 30 minutes of hypothermic ischemia (hypothermia-treated group), followed by 30 minutes of reperfusion in both groups. We recorded functional parameters and used electron spin resonance (ESR) spectroscopy to detect ascorbyl radicals, as markers of free-radical production, in samples of coronary effluents.. Functional parameters were stable in the 2 groups during pre-ischemic and ischemic periods. During reperfusion, coronary flow, left diastolic ventricular pressure, left ventricular developed pressure, and heart rate more rapidly recovered to values close to those obtained during the pre-ischemic period in the hypothermia-treated group than in the control group. Moreover, the post-ischemic contracture observed in the control group did not appear in the hypothermia-treated group. Finally, ESR analysis showed that the post-ischemic release of ascorbyl radicals decreased in the hypothermia-treated group.. These results demonstrate that the protective effect of hypothermia against functional injury caused by ischemia-reperfusion may decrease the free-radical burst at reperfusion.

Topics: Animals; Coronary Circulation; Dehydroascorbic Acid; Disease Models, Animal; Electron Spin Resonance Spectroscopy; Hypothermia, Induced; Myocardial Ischemia; Rats; Rats, Wistar; Recovery of Function; Reperfusion Injury; Ventricular Pressure