Abstract 20679: Nonselective and Selective Cyclooxygenase Inhibition Improve Cardiovascular Function in a Hypercholesterolemic Swine Model of Chronic Ischemia
Objective: The cardiovascular effects of nonselective cyclooxygenase (COX) and selective COX-2 inhibition remain controversial. We assessed the hypothesis that COX-inhibition alters myocardial and endothelial function in a hypercholesterolemic swine model of chronic ischemia.
Methods: Yorkshire swine fed high-cholesterol diet were made chronically ischemic by ameroid constrictor placement on the left circumflex artery. Animals were divided into three groups and given either no drug (HCC, n=8), non-selective COX inhibitor (Naproxen 440 mg/day, HCNS, n=8), or selective COX-2 inhibitor (Celecoxib 200 mg/day, HCCX, n=8). After 7 weeks, myocardial function, perfusion and microvessel reactivity in the ischemic territory were assessed. Tissue was analyzed for protein oxidation, VEGF expression, and capillary density.
Results: Hemodynamics and global ventricular function were similar between groups, but regional function in the ischemic territory as measured by horizontal segmental shortening was improved in HCNS and HCCX swine compared to HCC. Myocardial perfusion in the ischemic territory was somewhat improved in HCNS animals and significantly improved in HCCX compared to HCC, both at rest and during pacing. Microvessel relaxation response to adenosine 5′-diphosphate, an endothelium-dependent vasodilator, was improved in both HCNS and HCCX compared to HCC, while endothelium-independent vasodilation response to sodium nitroprusside was similar between groups. Protein oxidation was decreased in HCNS and HCCX compared to HCC, while VEGF expression was increased in HCNS and HCCX compared to HCC. Capillary density as measured by CD31 staining was decreased in the both the HCNS and HCCX groups (see table).
Conclusions: Selective and nonselective COX inhibition improve myocardial perfusion and function in a hypercholesterolemic model of chronic ischemia by improving vasorelaxation, decreasing oxidative stress, and increasing VEGF expression.
- © 2010 by American Heart Association, Inc.