Clinical/Translational Research Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Rationale: Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion. Objective: To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action. Methods and Results: Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor (TNF) was measured. The response of rat mesenteric arteries with intact ( E) and denuded ( E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21 5% and the aspirate plasma after stenting induced 95 8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B2, and TNF release into aspirate plasma increased by 1.9 0.2 mol/L, 25.6 3.1 pg/mL, and 19.7 6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNF did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside ( E, 3.3 10 ; E, 1.9 10 8 mol/L) and verapamil ( E, 8.3 10 ; E, 7.8 10 8 mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker. Conclusion: Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNF somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium. (Circ Res. 2011;108:344-352.)