Date of Defense
William Jackson, Biological Sciences
Leonard Beuving, Biological Sciences
J. Craig Hartman, Upjohn Company
The role of the enzyme nitric oxide synthase in myocardial ischemic preconditioning was investigated in an anesthetized, open-chest rabbit model of acute coronary occlusion. The nitric oxide synthase inhibitor, L-NAME, was administered to determine the effect of reduced endogenous nitric oxide production on the cardioprotective effects of myocardial preconditioning. Rabbits weighing 2.5-3.5 kg of either sex were instrumented for measurement of left ventricular pressure and systemic hemodynamics. Animals were then subjected to 30 minutes of coronary occlusion by temporary ligation of a branch of the left main coronary artery. Temporary ischemia was produced, followed by 120 minutes of reperfusion, after which the extent of myocardial necrosis (infarct size as a percent of area at risk) was determined by tetrazolium staining. Animals were selected to receive either L-NAME (animals were pretreated for 90 minutes with 100 ug/kg/min), L-NAME + ischemic preconditioning (5 minute occlusion followed by 10 minute reperfusion), a saline vehicle or ischemic preconditioning alone. While systemic hemodynamis of the saline control animals and those receiving preconditioning or L-NAME alone were stable throughout the experiments, the treatment group receiving L-NAME + myocardial ischemic preconditioning experienced a decrease in MAP, and a decrease in left ventricular +dP/dtmax during reperfusion. Myocardial infarct size of the treatment group receiving preconditioning alone (12 ± 2% *) was reduced as compared to that of the saline control rabbits (39 ± 2%), while infarct size for those rabbits receiving L-NAME + preconditioning (40 ± 2%) approached the control value (Mean ± SEM, * = p < 0.05). Myocardial area at risk for all treatment groups did not differ significantly from that of the saline control. The results obtained in this study indicate that inhibition of nitric oxide synthase with L-NAME abolishes the protective effect of myocardial preconditioning, and therefore nitric oxide may play an important role in the preconditioning phenomena.
Leva, Stacey, "Inhibition of Nitric Oxide Synthase with L-NAME Prevents Myocardial Ischemic Preconditioning" (1995). Honors Theses. 210.
Honors Thesis-Campus Only