Abstract 2315: Markedly Enhanced Activity of Endothelin-1 in Transplant Coronary Arteriosclerosis
| Autor: | Eric Larose, Dominik Behrendt, Scott Kinlay, Andrew Selwyn, Peter Ganz, James Fang |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Circulation. 116 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.116.suppl_16.ii_506-a |
| Popis: | Background: Coronary arteriosclerosis is the principal complication limiting long-term survival after heart transplantation. In humans, the mediators responsible for vascular proliferation and vasoconstriction typical of TCA are unknown. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen derived primarily from endothelial and mononuclear cells. We tested the hypothesis that ET-1’s biological activity is increased in TCA and that it may contribute to the pathogenesis and manifestations of TCA. We inhibited the ET A receptor by administering a specific antagonist BQ-123 into the coronary arteries in heart transplant recipients undergoing routine annual cardiac catheterization. We compared the coronary vasomotor responses to BQ-123 in subjects with angiographic evidence of TCA and subjects free of angiographic evidence of TCA. Methods: BQ-123 was infused into one proximal coronary artery (40nmol/min for 60min) of 18 subjects, age 18 –75, 6 +/− 4 years after transplantation. In each patient 3 coronary segments were studied in both the infused and in a non-infused control coronary artery (Total 108 segments). Changes from baseline in diameters of the infused arterial segments were compared to those of non-infused arterial segments at 15 minute intervals. Contribution of ET-1 to coronary constrictor tone was assessed by comparing vasodilation from BQ-123 infusion to dilation from intracoronary nitroglycerin (200μg bolus). Results: BQ-123 induced dilation in coronary arteries of transplanted patients (8.4% at 60 minutes, vs. −0.4% in noninfused arteries, p Conclusions: The endogenous biological activity of ET-1 is markedly increased in humans with TCA compared to those without evidence of TCA. This supports a role for ET-1 in the pathogenesis of TCA and suggests that therapeutic targeting of ET-1 may slow the development and manifestations of TCA in cardiac transplant recipients. |
| Databáze: | OpenAIRE |
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