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Sildenafil citrate augments myocardial protection in heart transplantation.
MedLine Citation:
PMID:  20098279     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Sildenafil citrate has been shown to induce myocardial protective effects in a variety of experimental settings. Whether these effects could be used to enhance myocardial protection afforded by crystalloid cardioplegia, volatile anesthesia and hypothermia during cardiac transplantation remains to be established. METHODS: We investigated the use of sildenafil-mediated cardioprotection in a rat model of heterotopic cardiac transplantation. Sildenafil citrate (0.7 mg/kg) was administered intravenously to the donor 30 min before onset of ischemia or 5 min before reperfusion in the recipient. In situ cardioplegic arrest was followed by an ischemic time of 3 or 6 hr, transplantation, and blood reperfusion. Myocardial functional recovery was studied in vivo by using a left ventricular balloon and cellular injury quantified by assay of troponin I release and apoptosis. RESULTS: Sildenafil preconditioning but not postconditioning significantly improved initial myocardial systolic and diastolic function after 3 hr of hypothermic cardioplegic arrest (114+/-4 mm Hg vs. 83+/-4 mm Hg generated pressure, [P<0.01]). The protective effect of sildenafil declined over a 3-hr period of reperfusion along with overall myocardial function, no longer reaching statistical significance at 3 hr. The protective effects of sildenafil were abolished by the putative blocker of the mitochondrial ATP sensitive potassium channel, 5-hydroxydecanoate, before sildenafil administration. Protein kinase C delta showed significant translocation after sildenafil administration in the donor. CONCLUSIONS: We conclude that sildenafil citrate pretreatment augments myocardial functional recovery after an ischemic time relevant to clinical cardiac transplantation. This effect is associated with protein kinase C activation/translocation and inhibited by 5-hydroxydecanoate.
Authors:
Phil Botha; Guy A MacGowan; John H Dark
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  89     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  169-77     Citation Subset:  IM    
Affiliation:
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. P.Botha@ncl.ac.uk
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