Document Detail

8-Br-cyclic GMP given during reperfusion improves post-transplant lung edema and free radical injury.
MedLine Citation:
PMID:  10703694     Owner:  NLM     Status:  MEDLINE    
Substitution of the NO-pathway reduces ischemia/reperfusion injury following lung transplantation. 8-Br-cGMP is a membrane permeable analogue of cGMP, the second messenger of NO. In this study the effect of continuous administration of 8-Br-cGMP on early graft function was evaluated. METHODS: Unilateral left lung transplantation was performed in 10 weight-matched pigs (23-30 kg). Donor lungs were flushed with 1.51 cold (1 degree C) LPD solution and preserved for 20 hours. In Group I (n = 5), 8-Br-cGMP (0.2 mg/kg/h) was given continuously over the entire observation time starting 15 min before reperfusion. Group II served as control, no 8-Br-cGMP was administered. In both groups, 250 microg PGE1 was injected into the pulmonary artery (PA) before flush. One hour after reperfusion the recipients contralateral right PA and bronchus were ligated to assess isolated graft function only. Extravascular lung water index (EVLWI), pulmonary vascular resistance, mean PA pressure, mean systemic arterial pressure and gas exchange were assessed during a 5-hour observation period. Lipid peroxidation as indicator for free radical mediated injury and neutrophil migration to the allograft were measured at the end of the assessment. RESULTS: EVLWI was significantly reduced in animals treated with 8-Br-cGMP (overall difference P = 0.024) with a peak 2 hours after reperfusion (Group I, 8.2+/-0.3 mg/ml vs Group II, 10.1+/-0.6 mg/ml; P = 0.039). Also in Group I the free radical mediated tissue injury was significantly lower when compared to Group II (Group I, 61.8+/-12.3 pmol/g vs Group II, 120.7+/-7.2 pmol/g; P = 0.006). A tendency towards a reduced neutrophil migration after 8-Br-cGMP infusion was shown; however, the changes in comparison to the control animals were not statistically significant (Group I, 1.0+/-0.2 deltaOD/mg/min vs Group II, 1.7+/-0.3 deltaOD/mg/min; P = 0.13). Pulmonary- and systemic hemodynamics, and allograft gas exchange did not differ between groups. CONCLUSIONS: The results indicate that substitution of the NO pathway by administration of the second messenger cGMP at the time of reperfusion improves post-transplant lung allograft function.
P Sandera; S Hillinger; U Stammberger; G Schoedon; M Zalunardo; W Weder; R A Schmid
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  19     ISSN:  1053-2498     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-15     Completed Date:  2000-03-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  173-8     Citation Subset:  IM    
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
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MeSH Terms
Cyclic GMP / analogs & derivatives*,  therapeutic use
Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors*
Extravascular Lung Water
Free Radicals
Lipid Peroxidation
Lung Transplantation*
Postoperative Period
Pulmonary Edema / drug therapy*
Random Allocation
Reperfusion Injury / physiopathology,  prevention & control*
Thiobarbituric Acid Reactive Substances
Transplantation, Homologous
Reg. No./Substance:
0/Free Radicals; 0/Thiobarbituric Acid Reactive Substances; 31356-94-2/8-bromocyclic GMP; 7665-99-8/Cyclic GMP; EC GMP-Dependent Protein Kinases

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