Relation of Coronary Hypersensitivity to Serotonin in Cardiac Transplant Recipients to Vessel Wall Morphology and Effect of Vitamin C

Coronary hypersensitivity to serotonin promotes platelet aggregation, entailing the progression of the atherosclerotic process. This abnormality is a common finding in cardiac transplant recipients and may be triggered by reactive oxygen species, which plays a main role in the inflammatory process. Hence, this study aimed to determine the influence of intimal hyperplasia on this abnormality and its reversibility after acute supplementation with the superoxide anion scavenger vitamin C. Therefore, intracoronary injections of serotonin (3 μg), bradykinin (600 ng), and nitroglycerin (isosorbide dinitrate 200 μg) were administered to 21 cardiac transplant recipients (1 year after transplantation) with normal coronary angiographic results; the serotonin injections were repeated after intracoronary vitamin C supplementation (40 mg/min for 14 minutes). In the segments in which serotonin effects were the most pronounced, the diameter changes were measured by quantitative angiography, and vessel wall morphology was studied by intravascular ultrasound (IVUS). The IVUS examination revealed moderate to severe intimal thickening (total area − luminal area/total area) in 9 patients (group 1) of 25 ± 2%, compatible with the early stage of graft vasculopathy. In this group, hypersensitivity to serotonin remained unchanged after intracoronary vitamin C supplementation, from −21 ± 3% (percentage from baseline) to −25 ± 3%, whereas in the other 12 patients with mild intimal thickening (9 ± 1%; group 2), hypersensitivity to serotonin was attenuated from −20 ± 5% to −4 ± 6% (p <0.01). In contrast, the responses to bradykinin and isosorbide dinitrate were similar in the 2 groups. In group 1, plasma levels of high-sensitivity C-reactive protein and proinflammatory cytokines (interleukin-6 and -8) were significantly enhanced. For all the patients studied, the effect of vitamin C on the response to serotonin was significantly correlated with the intimal thickening. In conclusion, at 1 year after transplantation, morphologic changes compatible with the early stage of the graft vasculopathy are accompanied by hypersensitivity to serotonin unresponsive to vitamin C, despite a relatively preserved endothelial function (unaltered response to bradykinin).