Date of Defense

Summer 7-18-1991


Biological Sciences

First Advisor

Fred Mandel, Upjohn Company

Second Advisor

Leonard Beuving, Biology

Third Advisor

Michael McCarville, Chemistry


The effect of free radicals formed during reperfusion therapy to an ischemic area was simulated by examining the effect of three free radical generating systems (h2O2, h2O2/FeCl3, cumene hydroperoxide/CuSO4) on membrane vesicles. The cumene hydroperoxide/copper system proved to be the most reliable of the three solutions in the production of free radicals and in decreasing the activity of both Na,K-APTase and the Na/Ca exchanger protein in a consistent dose-dependent manner. During the examination of calcium uptake in cardiac membrane vesicles it was observed that under experimental conditions, Na-independent uptake is not a function of free radical formation. However, Na-Dependent uptake and, therefore, the viability of the Na/Ca exchanger decreases with increased free radical production. These results indicate that inhibition of the exchanger occurs prior to damage done to the membrane itself. Both the Na, K-ATPase and the Na/Ca exchanger were partially protected from free radical damage in the presence of the Upjohn drug U78517F.

Access Setting

Honors Thesis-Campus Only