Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits

Background: Hypercholesterolemia predisposes to coronary artery disease and causes endothelial dysfunction; some reports suggest that endothelial derived substances are involved in ischemic preconditioning. Objective: Our aim was to examine the possibility that preconditioning maybe attenuated in a clinically relevant animal model of hypercholesterolemia with atherosclerosis. Methods: Male rabbits were fed with cholesterol enriched diet and then divided into two groups (A and B) without and with preconditioning, respectively. A second series of rabbits fed a normal diet were similarly divided into two groups (C and D) without and with preconditioning, respectively. All the animals were subjected to 30 min ischemia and 180 min reperfusion. Blood samples were collected for cholesterol assessment; arterial and heart samples were harvested at the end for histopathological examination. Infarct (I) and risk areas (R) were delineated with Zn-Cd particles and TTC staining. Results: Cholesterol in groups A and B was 58.3 +/- 8.7 mg% at baseline and 1402 +/- 125 mg% at 8 weeks (P < 0.0001) and in groups C and D 57.5 +/- 5.8 mg% before the surgical procedure. I/R% was 39.3 +/- 6.3% in group A, 16.7 +/- 3.9% in B (P < 0.01), 41.4 +/- 7.5% in C and 10.8 +/- 3.3% in D (P < 0.01). Conclusion: We conclude that preconditioning is unlikely to be attenuated by hypercholesterolemia. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.