EFFECTS OF HYPERCHOLESTEROLEMIA ON PHYSIOLOGICAL RECRUITMENT OF CORONARY VASCULAR RESERVE IN SWINE

1. 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 th e hypothesis that hypercholesterolaemia impairs coronary vascular rese rve in an intact animal. 2. Domestic swine, maintained on a regular (n =9) off a 2% high-cholesterol (n=9) diet for 3 months were instrumente d with a catheter in the left atrium for microsphere injection, a cath eter in the anterior interventricular vein for venous sampling and an 82% stenosis in the left anterior descending artery, Papaverine was us ed to determine coronary vascular reserve, Regional coronary flow as r eflected 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+/-50mg/dl versus 99+/-10 mg/dl, P<0.001), Baseli ne haemodynamics were similar between groups, Baseline transmural flow and its augmentation with papaverine were comparable in the two group s in the control (circumflex) and stenosed (left anterior descending a rtery) zones, In both groups, perfusion increased in the control zone in response to increased oxygen demand, whereas in the stenosis zone n o increase was observed in either group (P not significant for normal versus high cholesterol diet), Endocardial flow reserve in the stenosi s zone was exhausted in both groups, Epicardial flow in the stenosis z one increased significantly in the normal (P<0.02) but not in the hype rcholesterolaemic animals (P not significant). 4. The endocardial/epic ardial ratio in the control zone at baseline revealed greater endocard ial dominance in the normal compared with the hypercholesterolaemic an imals (1.35 versus 1.10, P<0.01), With papaverine, similar ratios indi cated a similar reserve potential in both groups, During increased oxy gen demand, normal animals continued to demonstrate endocardial domina nce whereas it diminished in the hypercholesterolaemic group, In the s tenosis zone, endocardial blood flow dominated at baseline in the norm al animals and to a lesser extent in the hypercholesterolaemic animals (1.30 versus 1.10, P=0.10), During increased oxygen demand, endocardi al dominance decreased significantly in both groups of animals; howeve r, it remained greater than 1.0 only in the normal animals. 5. Exposur e to elevated cholesterol levels did not impair an animal's ability to augment coronary blood flow in response to an increase in oxygen dema nd, In contrast to this lack of effect on recruitment of coronary rese rve, regional coronary blood flow was altered In the hypercholesterola emic animals.