| Time course of coronary endothelial dysfunction in acute untreated rejection after heterotopic heart transplantation. | |
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MedLine Citation:
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PMID: 9229295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Endothelial dysfunction is one of the early events leading to atherosclerosis. It occurs early after orthotopic heart transplantation and precedes the appearance of accelerated graft coronary artery disease believed to stem from chronic rejection of the endothelium. Acute rejection may contribute to the development of graft vasculopathy. METHODS: To assess the time course and specific mechanisms of coronary endothelial dysfunction in acute untreated rejection, a swine model of retroperitoneal heterotopic heart transplantation was used. Large white swine (age 10 +/- 2 weeks, weight 25 +/- 5 kg) were serum-typed for class I antigen of the swine leukocyte antigen system and selected to ensure a similar degree of incompatibility. Donor hearts were preserved with normothermic blood cardioplegia and regional hypothermia; the mean ischemic time was 64 +/- 15 minutes. Myocardial contractility decreased from day 5 (normal) to day 14 (weak), but electrical activity was preserved. All coronary arteries were patent, and International Society for Heart and Lung Transplantation grade 4 rejection was present in all hearts beyond 5 days. The endothelial function of epicardial coronary arterial rings of native and transplanted hearts was studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution and compared 1, 5, 9, and 14 days after transplantation. RESULTS: Maximal endothelium-independent relaxations were unaffected at all stages. Endothelium-dependent relaxations to serotonin and alpha 2-adrenergic agonist UK 14304 (which activate receptors coupled to Gi-proteins) and to sodium fluoride (a direct G-protein activator) deteriorated progressively over time. At 14 days maximal relaxations to the calcium ionophore A23187, adenosine diphosphate, and bradykinin were also reduced, but to a lesser degree than those to serotonin and sodium fluoride. Histomorphometric studies of the allograft coronary artery rings showed progressive intimal hyperplasia from day 5 to day 14, with an increase in the incidence from 29% +/- 8.3% to 61.5% +/- 12%. CONCLUSIONS: These studies show that endothelial dysfunction in untreated acute rejection after heart transplantation develops beyond 5 days and initially involves G-proteins; the dysfunction worsens over time to finally affect all endothelial mechanisms and vascular smooth muscle. The progression of the associated intimal hyperplasia parallels the alteration in endothelial function, suggesting a permissive role of the dysfunction in the development of this acute form of coronary graft vasculopathy. |
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Authors:
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L P Perrault; J P Bidouard; P Janiak; N Villeneuve; P Bruneval; J P Vilaine; P M Vanhoutte |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Volume: 16 ISSN: 1053-2498 ISO Abbreviation: J. Heart Lung Transplant. Publication Date: 1997 Jun |
Date Detail:
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Created Date: 1997-09-18 Completed Date: 1997-09-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9102703 Medline TA: J Heart Lung Transplant Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 643-57 Citation Subset: IM |
Affiliation:
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Cardiovascular Division, Institut de Recherches Servier, Suresnes, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Disease / pathology, physiopathology Coronary Vessels / pathology, physiology* Electrocardiography Endothelium, Vascular / pathology, physiopathology* Female Fibromuscular Dysplasia / pathology, physiopathology Graft Rejection / pathology, physiopathology* Heart Transplantation / pathology, physiology* Male Nitric Oxide / physiology Nitric Oxide Synthase / physiology Swine Transplantation, Heterotopic / pathology, physiology* Vasodilation / physiology |
| Chemical | |
Reg. No./Substance:
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10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase |
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