Increased severity of acute myocardial ischemia in experimental atheroscelerosis

Abstract

We investigated the effects of acute myocardial ischemia (MI) in a rabbit model of atherosclerosis to determine whether atherosclerosis augments the severity of damage produced in the ischemic myocardium. Normal rabbits were fed a control rabbit chow diet or a diet enriched with either 2% cholesterol or 0.5% cholesterol for 10-12 weeks prior to induction of MI. Plasma cholesterol concentrations in the cholesterol-fed rabbits were 1697 +/- 70 mg/dl (2%) and 1056 +/- 51 mg/dl (0.5%) vs. 61 +/- 12 mg/dl for the non-cholesterol-fed rabbits. All rabbits were observed for 5 h following induction of MI or sham MI. At the conclusion of the experiment, tissue biopsies from the MI region and non-MI (NMI) regions were taken and analyzed for two indicators of the severity of MI--myocardial creatine kinase (CK) activity and free amino-nitrogen concentration. Atherosclerosis was confirmed histologically in coronary artery and aortic specimens. No difference was found among any group with respect to heart rate (HR), mean arterial blood pressure (MABP), or pressure-rate index (HR x MABP/1000, a measure of myocardial oxygen demand). Myocardial CK loss (NMI - MI) was significantly greater for the 2% and 0.5% cholesterol groups (7.3 +/- 1.3 and 4.9 +/- 0.7 IU/mg protein, respectively, P less than 0.05) than in the nonatherosclerotic group (2.5 +/- 0.4 IU/mg protein; P less than 0.001 for 2% and P less than 0.01 for 0.5%). Increased severity of MI was confirmed by a significantly greater myocardial loss of free amino-nitrogen (NMI - MI) in the two atherosclerotic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment.

“…In those animals undergoing MI, the ligature remained tied tightly for the entire 5-h observation period. This procedure allowed us to achieve a consistent ischemic zone in the MI rabbits (1,20). The pressure-rate index (PRI), calculated as the product ofMABP and HR divided by 1,000, was used as an index of myocardial oxygen demand.…”

“…Hypercholesterolemia and ensuing atherosclerosis have been implicated in the pathophysiology of coronary artery disease and myocardial ischemia (MI)' (1)(2)(3). Elevated plasma cholesterol concentrations may be important in the initiation ofischemia and also in the subsequent propagation ofischemic damage (1, 2, 4).…”

“…Elevated plasma cholesterol concentrations may be important in the initiation ofischemia and also in the subsequent propagation ofischemic damage (1, 2, 4). There is also evidence that elevated plasma cholesterol concentrations may act to inhibit the ability of the 1. Abbreviations used in this paper: ACh, acetylcholine; CK, creatine kinase; CPP, coronary perfusion pressure; EDRF, endothelium-derived relaxing factor; HMGCoA, 3-hydroxy-3-methylglutaryl-coenzyme A; MABP, mean arterial blood pressure; PAF, platelet-activating factor; PRI, pressure-rate index; KH, Krebs-Henseleit solution; MI, myocardial ischemia.…”

“…We have recently developed a model of acute myocardial ischemia in cholesterol-fed rabbits (1). The rabbits are chronically fed a cholesterol-enriched diet that produces several of the pathophysiologic sequelae which occur during atherosclerosis.…”

Effects of Hypercholesterolemia on Myocardial Ischemia-Reperfusion Injury in LDL Receptor–Deficient Mice

“…Previous studies investigating the effects of MI-R in the setting of hypercholesterolemia have focused primarily on rabbit models of ischemia alone 4,5 or on I-R. 6 -8 Osborne et al 4 reported that creatine kinase release after 5 hours of regional ischemia was significantly greater in rabbits fed a high-cholesterol diet (HCD) for 10 to 12 weeks. Furthermore, a subsequent study 5 of MI in hypercholesterolemic rabbits reported an increased severity of myocardial tissue injury that was significantly reversed by treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor lovastatin.…”