We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino-atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148+/-11 to 103+/-20 beats/min, p<0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136+/-22 beats/min), animals were separated into a low-heart-rate (LHR) group (111+/-16 beats/min, n=12) and a high-heart-rate (HHR) group (150+/-16 beats/min, n=5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross-sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01+/-1.19 compared with 0.76+/-0.42 mm2 for lesion area [p<0.02] and 30.7+/-4.4% compared with 15.2+/-7.3% for stenosis [p<0.002]). When the single section with the largest lesion at each bifurcation was considered, all in the HHR group but only half of those in the LHR group had greater than 25% stenosis (p<0.03). Artery size, as indicated by the area encompassed by the internal elastic lamina, increased with plaque area. For the sections with little or no plaque immediately proximal or distal to the bifurcation, the internal elastic lamina area was similar for both groups. We conclude that axial and circumferential plaque distribution about the cynomolgus monkey carotid bifurcation is similar to that observed in humans, that plaque formation induced compensatory artery enlargement, and that plaque progression was retarded by lowered heart rate. The findings suggest that the conditions that determine plaque location and adaptive modeling in human atherogenesis also prevail in the cynomolgus monkey.
