Date of Award

1995

Degree Type

Thesis

Degree Name

Master of Science in Pharmacology and Toxicology

Department

Pharmacology and Toxicology

First Advisor

Robert L. Rodgers

Abstract

The phenomena of cardiac ischemia and reperfusion involve substantial, multifactorial pathophysiologic derangements, the attenuation of which is vital for the functional recovery and viability of the heart. It has been proposed that methylene blue (MB) may decrease the damage associated with ischemia and reperfusion, in part by the suppression of oxyradical generation and by the enhancement of ATP recovery. In the present study, we tested the effect of pretreating isolated working rat hearts with MB prior to imposing ischemia and reperfusion. Hearts were treated for ten minutes with either 0.1 μM, 1.0 μM, or 10.0 μM MB, or given no treatment, prior to thirty-five minutes of zero flow, global ischemia and ten minutes of subsequent reperfusion. The mechanical performance and electrical activity of the hearts were monitored throughout the experiments. In addition, aliquots of coronary artery effluent were periodically collected for biochemical analyses. The cardiac tissue was frozen at the end of the experiments and subsequently assayed to estimate the extent of membrane phospholipid peroxidation. The ir:icidence and duration of ventricular fibrillation occurring during reperfusion in the MB-treated hearts were not significantly different from the untreated hearts. The measurement of coronary artery flow during reperfusion was similar in both untreated and treated groups. The appearance of lactate dehydrogeriase in the coronary artery effluent of treated hearts approximated those levels measured in untreated hearts. The calculated indices of electromechanical recovery did not differ significantly from the value obtained for the untreated pool. There were comparable levels of thiobarbituric acid reactive substances (TSARS) detected in the cardiac tissue from treated and untreated groups. Since MB did not exhibit significant protective effects during ischemia and reperfusion, we also conducted an experiment with 100 nM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor. Previous studies with EHNA pretreatment in our laboratory have demonstrated measurable cardioprotection, however this observation was not reproduced in the present study. In summary, we did not observe cardioprotective effects using several concentrations of MB in our isolated working rat heart model of global ischemia/reperfusion injury.

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