RESPONSE OF HUMAN CORONARY-ARTERIES TO SEROTONIN AFTER INJURY BY CORONARY ANGIOPLASTY

Background. Atheroslerotic stenoses that have exaggerated vasomotor responses are especially prone to restenosis after coronary angioplasty. Experimental studies show that vasomotor responses in normal vessels are altered by acute mechanical injury, an alteration that in part reflects changes in the functional characteristics of endothelium that has regenerated after injury. Methods and Results. We examined, by quantitative coronary arteriography, the response of dilated and control coronary segments to intracoronary infusions of graded doses of serotonin, an endothelium-dependent vasoactive agent, and to intracoronary injection of isosorbide dinitrate, an endothelium-independent smooth muscle dilator in 15 patients who had undergone a single percutaneous transluminal coronary angioplasty procedure and who had no clinical features of variant angina. Dose-dependent constriction to serotonin occurred at all measured sites. The mean+/-SEM diameter reductions, expressed as percent reduction in baseline diameter that was observed at proximal (18.1+/-2.9, 18.8+/-2.2) and distal (30.9+/-4.4, 35.4+/-5.3) control sites in the dilated and nondilated vessels, respectively, at the highest dose, were similar. The degree of constriction in distal segments was significantly (P<.01) greater than that in proximal segments. Total or subtotal occlusion occurred at the angioplasty site in 4 patients at the highest infused dose (10(-4) mol/L). The mean percent reduction in baseline diameter at previously dilated sites (53.8+/-5.9) at this dose was significantly (P<.05) greater than that observed at the adjacent proximal control sites and similar to that observed at distal control sites. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. Conclusions. In dilated and nondilated vessels, serotonin caused significantly more marked constriction in distal than in proximal vessel segments. In dilated vessels, the vessel segments that had been subjected to angioplasty had a constrictor response to serotonin that was more marked than at adjacent proximal control sites and equivalent to that in the distal vessel segments. This enhanced constrictor response could be related to changes in endothelial cell function after regeneration or to hyperreactivity of smooth muscle cells at the angioplasty site.