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 aminonitrogen 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 × 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,PPP<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. Moreover, there was a higher mortality due to sudden cardiac death following coronary occlusion in the 2% cholesterol-fed rabbits—33% versus 0% for the 0.5% cholesterol-fed or control rabbits. Thus, atherosclerosis exacerbates the degree of ischemic damage independent of myocardial oxygen demand and increases mortality in rabbits following coronary artery occlusion.