Abstract 10176: Serotonin Blockade with Ketanserin Attenuates ST-segment Depression and Myocardial Perfusion Defects Secondary to Collagen-induced Platelet Activation in Swine
Background: The exact pathophysiologic mechanism underlying ST-segment depression myocardial ischemia remains controversial. Whereas most authors traditionally attribute it to partial epicardial coronary occlusion, current research emphasizes the pivotal role of platelet activation, shifting our focus from the degree of stenosis to the underlying prothrombotic processes. We sought to study the effect of serotonin, as a platelet-derived vasoactive substance, on myocardial perfusion and ECG markers of ischemia, and to evaluate its potential as a therapeutic target.
Methods: Fifteen male Landrace pigs received 10-minute intracoronary infusions of collagen-activated platelet-rich plasma (PRP), before (PRP1) and after (PRP2) a 30-minute intravenous infusion of ketanserin (1 mg/kg) for serotonin blockade.
Results: Significant ST-segment depression was observed upon infusion of PRP1. Neutron-activated microspheres revealed the predominance of subendocardial ischemia after PRP1 through a marked decrease in regional myocardial blood flow (RMBF) in the endocardium of the ischemic territory, resulting in a significant decline in the endocardial/ epicardial flow ratio. After ketanserin infusion, ECG and RMBF defects occurred to a lesser extent with PRP2. However, in one control animal that did not receive ketanserin, ECG and perfusion defects were more pronounced with PRP2. No significant changes were observed in the left anterior coronary artery diameter measured by coronary angiography or in epicardial blood flow, which confirms the limited impact of epicardial lesions in ST-segment depression myocardial ischemia.
Conclusion: Platelet activation results in the release of vasoactive and pro-aggregatory substances that, even in absence of flow-limiting stenosis, may impair coronary microvascular perfusion leading to subendocardial ischemia and ST-segment depression. Serotonin blockade with ketanserin could attenuate ECG and perfusion defects resulting from platelet activation. These findings highlight the potential of platelet activation end-products, particularly serotonin, as novel pharmacotherapeutic targets for non-invasive management of non-ST-segment elevation acute coronary syndromes.
- © 2010 by American Heart Association, Inc.