The endothelium participates in the regulation of coronary vascular tone. As evidence exists from studies performed on epicardial vessels that hypercholesterolaemia impairs endothelial function, we tested the hypothesis that hypercholesterolaemia impairs coronary vascular reserve in an intact animal. 2. Domestic swine, maintained on a regular (n = 9) or a 2% high-cholesterol (n = 9) diet for 3 months were instrumented with a catheter in the left atrium for microsphere injection, a catheter in the anterior interventricular vein for venous sampling and an 82% stenosis in the left anterior descending artery. Papaverine was used to determine coronary vascular reserve. Regional coronary flow as reflected by perfusion (microsphere measurement), lactate consumption, oxygen consumption and haemodynamics were obtained at baseline, after 10 mg of papaverine and after atrial pacing at a rate of 120 beats/min and 150 beats/min. 3. Cholesterol was elevated in animals on the high cholesterol diet (350 +/- 50 mg/dl versus 99 +/- 10 mg/dl, P < 0.001). Baseline haemodynamics were similar between groups. Baseline transmural flow and its augmentation with papaverine were comparable in the two groups in the control (circumflex) and stenosed (left anterior descending artery) zones. In both groups, perfusion increased in the control zone in response to increased oxygen demand, whereas in the stenosis zone no increase was observed in either group (P not significant for normal versus high cholesterol diet). Endocardial flow reserve in the stenosis zone was exhausted in both groups. Epicardial flow in the stenosis zone increased significantly in the normal (P < 0.02) but not in the hypercholesterolaemic animals (P not significant). 4. The endocardial/epicardial ratio in the control zone at baseline revealed greater endocardial dominance in the normal compared with the hypercholesterolaemic animals (1.35 versus 1.10, P < 0.01). With papaverine, similar ratios indicated a similar reserve potential in both groups. During increased oxygen demand, normal animals continued to demonstrate endocardial dominance whereas it diminished in the hypercholesterolaemic group. In the stenosis zone, endocardial blood flow dominated at baseline in the normal animals and to a lesser extent in the hypercholesterolaemic animals (1.30 versus 1.10, P = 0.10). During increased oxygen demand, endocardial dominance decreased significantly in both groups of animals; however, it remained greater than 1.0 only in the normal animals. 5. Exposure to elevated cholesterol levels did not impair an animal's ability to augment coronary blood flow in response to an increase in oxygen demand. In contrast to this lack of effect on recruitment of coronary reserve, regional coronary blood flow was altered in the hypercholesterolaemic animals.
