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S R Powell

Publications and source records attributed to S R Powell.

6 recordsLinked to original sources
PubMed1992

Mediatory role of copper in reactive oxygen intermediate-induced cardiac injury.

In this report the mediatory role of copper in cardiac injury produced by reactive oxygen intermediates was examined. Isolated rat hearts were perfused with Krebs-Henseleit buffer containing 0.25 mM ascorbate plus varying concentrations of copper-bis-histidial for up to 60 min. Using salicylate as a probe, OH generation by this system was demonstrated. Copper or ascorbate alone had minimal effect on cardiac function as determined by heart rate, coronary flow, left ventricular systolic pressure development, end diastolic pressure and +/- dP/dtmax. Copper, from 0.5 microM to 20 microM, and ascorbate, 0.25 mM, resulted in concentration-dependent decreases in all of the experimental variables. Treatment with 5 or 20 microM copper resulted in complete loss of cardiac function within 40 and 30 min, respectively. By 30 min, 5 microM copper had resulted in increased end diastolic pressure to greater than 40 mmHg. By 60 min, perfusion with 1 microM copper resulted in almost 100% loss of function and end diastolic pressure greater than 25 mmHg. Copper, 0.5 microM, also decreased cardiac function, but to a lesser degree. Catalase, 100 units/ml, was effective in preventing the copper-ascorbate induced cardiac damage while superoxide dismutase, 25 units/ml, was ineffective. Observations by light and electron microscopy demonstrated patchy regions with vacuolization corresponding to swollen mitochondria. These results clearly demonstrate that copper-catalyzed redox reactions can induce cardiac injury via a mechanism which appears to be related to the production of OH.

Animals↗
PubMed1992

Recent advances in the role of reactive oxygen intermediates in ischemic injury. I. Evidence demonstrating presence of reactive oxygen intermediates; II. Role of metals in site-specific formation of radicals.

This article has attempted to bring the reader up to date on advances in selected facets of the area of reactive oxygen intermediate-induced ischemic injury. Specifically, we have discussed the more recent reports that provide evidence for the presence of these species in reperfused ischemic tissue. In addition, we have attempted to introduce the reader to the relatively new concept of "site-specific" formation of radicals and how the use of "push-pull" techniques, such as chelation by high-affinity chelators or displacement by non-redox-active metals such as zinc, may decrease postischemic reperfusion injury. Finally, we have identified a class of compounds that affect the oxidation state of redox-active metals, and have demonstrated how these compounds may also represent a new therapeutic modality. In conclusion, both academic and nonacademic surgeons should have profited from reading this article. For the academic surgeon, who may do research, several new cytoprotectants requiring further study in both in vitro and in vivo models have been identified. For the nonacademic surgeon in clinical practice the realization that there are several promising areas of research that may yield new therapies to mitigate postischemic reperfusion injury should have been gained.

Animals↗
PubMed1991

Cardiac reperfusion damage prevented by a nitroxide free radical.

Experimental evidence is presented that directly links ischemia/reperfusion injury to the formation of oxygen-derived free radicals. 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO)--a stable nitroxide radical that disproportionates superoxide radicals and oxidizes reduced metal ions required for OH. formation--was tested for its ability to prevent reperfusion damage in the isolated rat heart subjected to regional ischemia. Severe reperfusion arrhythmia--ventricular fibrillation and ventricular tachycardia--were prominent in control hearts, and their duration was significantly reduced by the presence of 0.4 or 1 mM TEMPO. TEMPO also repressed both postischemic release of lactate dehydrogenase and OH. formation. TEMPO slowed the heart rate, but compensatory pacing did not alter the dramatic effect of the nitroxide on reperfusion arrhythmia. TEMPO was partially protective when introduced at the end of ischemia but had no effect when added 1 min into reperfusion. It was concluded that both reperfusion arrhythmia and cell damage were directly related to oxidative damage incurred during the critical first minute of reperfusion. TEMPO strongly protected against reperfusion injury by preventing the formation of OH. and not by decreasing heart rate or by direct suppression of arrhythmia.

Animals↗
PubMed1991

The effect of chronic administration of doxorubicin on the rat cardiac and hepatic glutathione redox system.

The effect of chronic administration of doxorubicin on the rat heart and liver glutathione redox system was studied. Rats were administered doxorubicin, 1 mg/kg, ip., three times a week, on Monday, Wednesday and Friday. One week was skipped and then the cycle repeated for a total of one, four, seven or ten doses. It was determined that treatment in this manner had no effect on rat heart glutathione, glutathione peroxidase or glucose-6-phosphate dehydrogenase, at any of the time intervals tested. However, hepatic glutathione content was found to be moderately increased after the fourth dose and glucose-6-phosphate dehydrogenase activity was found to be markedly increased after the seventh and tenth doses. Hepatic glutathione peroxidase was not affected. These results suggest that the cardiac glutathione redox system does not respond to chronic administration of doxorubicin. In contrast, the hepatic systems do respond, which may explain the apparent resistance of this organ to doxorubicin toxicity.

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