Document Detail


Time course of coronary endothelial dysfunction in acute untreated rejection after heterotopic heart transplantation.
MedLine Citation:
PMID:  9229295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
L P Perrault; J P Bidouard; P Janiak; N Villeneuve; P Bruneval; J P Vilaine; P M Vanhoutte
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  1997-09-18     Completed Date:  1997-09-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  643-57     Citation Subset:  IM    
Affiliation:
Cardiovascular Division, Institut de Recherches Servier, Suresnes, France.
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MeSH Terms
Descriptor/Qualifier:
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:
10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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