Author(s): McFadden EP, Clarke JG, Davies GJ, Kaski JC, Haider AW,
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Abstract BACKGROUND: Serotonin, a major product of platelet activation, has potent vasoactive effects in animal models, but its role in human coronary artery disease remains largely speculative. METHODS: Using quantitative coronary angiography, we compared the effects of the intracoronary infusion of graded concentrations of serotonin (10(-7) to 10(-4) mol per liter) on coronary vessels in two groups of patients with different clinical presentations of coronary disease (nine with stable angina and five with variant angina), with the effects in a control group of eight subjects with normal vessels on angiography. RESULTS: Normal coronary vessels had a biphasic response to intracoronary serotonin: dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4) mol per liter. Vessels in patients with stable angina constricted at all concentrations, with mean (+/- SEM) maximal decreases in diameter of 23.9 +/- 3.6, 33.1 +/- 3.9, and 41.7 +/- 3.1 percent from base line in proximal, middle, and distal segments at a serotonin concentration of 10(-4) mol per liter. Smooth segments constricted more than irregular segments (42.0 +/- 4.6 vs. 21.1 +/- 1.6 percent). Four patients with stable angina had a marked reduction in collateral filling. All the patients with stable angina had angina during the intracoronary infusion of serotonin, and electrocardiographic changes were noted in six. All the patients with variant angina had angina, electrocardiographic changes, and localized occlusive epicardial coronary-artery spasm at concentrations of 10(-6) (n = 2) or 10(-5) (n = 3) mol per liter. CONCLUSIONS: Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels. Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina. These findings suggest that serotonin, released after the intracoronary activation of platelets, may contribute to or cause myocardial ischemia in patients with coronary artery disease.
This article was published in N Engl J Med
and referenced in Anatomy & Physiology: Current Research