Coronary hemodynamic determinants of epicardial artery vasomotor responses during sympathetic stimulation in humans.

Sympathetic stimulation by cold-pressor testing induces a complex interplay between adrenergic receptor stimulation, humoral and local metabolic factors, and alterations in coronary perfusion pressure. Since the endothelium importantly modulates the effect of neurohumoral stimulation, we evaluated the coronary hemodynamic determinants of epicardial artery vasomotor responses to cold-pressor testing in 12 normal patients with intact endothelial function, and in 20 patients with early atherosclerosis, demonstrating a dysfunctional endothelium. Endothelial function was assessed by intracoronary infusion of the endothelium-dependent dilator acetylcholine. Vasomotor responses were examined by quantitative coronary angiography and continuous intracoronary flow velocity measurements using a Doppler catheter. All coronary artery segments demonstrating a dilator response to intracoronary acetylcholine also vasodilated in response to cold-pressor testing by 19.7 +/- 8.2% (mean +/- 1 SD). In contrast, all arteries with evidence of atherosclerosis demonstrated a vasoconstrictor response during cold pressor testing with an area reduction by 18.4 +/- 7.5%. The systemic hemodynamic variables heart rate and mean aortic pressure increased by comparable amounts in both groups of patients during cold pressor testing, indicating comparable increases in myocardial workloads. There was a significant positive relation between increases in blood flow and changes in arterial luminal area. Increases in blood flow were closely related to increases in mean aortic pressure in normal epicardial vessels, but this relation was blunted in vessels with a dysfunctional endothelium. Estimated shear stress changes within the epicardial conductance vessels were significantly lower in normal compared to atherosclerotic arteries. Thus, the increase in coronary blood flow is an important hemodynamic determinant of epicardial artery dilation in normal arteries during cold pressor testing. On the other hand, the vasodilator response limits increases in shear stress for a given increase in blood flow. In contrast, the failure of atherosclerotic arteries to dilate, despite increased myocardial demands, exaggerates increases in local shear stress in relation to changes in flow.