Regional coronary perfusion and bioenergetics in experimental atherosclerosis

The effects of experimental coronary atherosclerosis on myocardial high energy phosphates and regional coronary perfusion and oxygen delivery were studied. Hypercholesterolemic (HC) New Zealand white rabbits developed mild to moderate coronary vascular disease in 4 months when serum cholesterol levels were maintained at 1500--2000 mg/dl. Resting left ventricular levels of creatine phosphate, adenosine triphosphate (ATP), and the cellular energy charge were unaltered after 2 months of diet but were decreased after 4 and 6 months. Tissue lactate and the lactate/pyruvate ratio were increased after 4 months, suggesting mild tissue ischemia. The regional blood flow rate was measured in rabbits given pentobarbital after 6 months of diet using labeled microspheres, and the response to stress was tested after 5 minutes of hypoxic ventilation (5% O2/N2). The percentage of cardiac output to subendocardium (endo) and subepicardium (epi) in HC rabbits and that in control animals were similar at rest, but unlike that of control animals, the endo perfusion did not increase significantly in HC animals during hypoxic stress. Baseline regional left ventricular oxygen deliveries were similar between groups, but the baseline endo/epi oxygen delivery ratio was reduced in HC rabbits. In control rabbits hypoxia did not alter total O2 delivery, and the endo/epi oxygen delivery ratio was constant, whereas hypoxia in HC animals produced a decrease in total oxygen delivery and a further decrease in the endo/epi oxygen delivery ratio. Thus, moderate long-term coronary occlusive disease produced alterations in the distribution of coronary perfusion that are similar to those after acute partial occlusion, ie, selective reductions in blood flow and oxygen delivery to subendocardium. These results may relate to the pathogenesis of subendocardial infarction in man, which often occurs in the absence of complete coronary occlusion.