Document Detail


Myocardial protection in beating heart cardiac surgery: I: pre- or postconditioning with inhibition of es-ENT1 nucleoside transporter and adenosine deaminase attenuates post-MI reperfusion-mediated ventricular fibrillation and regional contractile dysfunction.
MedLine Citation:
PMID:  22329983     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine the role of the p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 (es-ENT1) in postmyocardial infarction reperfusion injury-mediated ventricular fibrillation and regional dysfunction. We used erythro-9 (2-hydroxy-3-nonyl)-adenine and p-nitrobenzylthioinosine to inhibit both adenosine deamination and transport in a canine model of off pump acute myocardial infarction.
METHODS: Anesthetized adult dogs (n = 37), instrumented to monitor the percentage of systolic segmental shortening and wall thickening using sonomicrometry, underwent 90 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Myocardial coronary blood flow, adenosine triphosphate pool, infarct size, and the incident of ventricular fibrillation and cardioversion were also measured. The dogs received an intravenous infusion of the vehicle (control) or 100 μM of erythro-9 (2-hydroxy-3-nonyl)-adenine and 25 μM p-nitrobenzylthioinosine before ischemia (preconditioning group) or just before reperfusion (postconditioning group).
RESULTS: In the control group, adenosine triphosphate depletion was associated with the accumulation of more inosine than adenosine during ischemia and washed out during reperfusion. Myocardial adenosine and inosine were the major nucleosides in the pre- and postconditioning groups during ischemia and remained detectable during reperfusion. In both groups, recovery of systolic segmental shortening and wall thickening and a reduction in the incidence of ventricular fibrillation (P < .05 vs the control group) coincided with retention of myocardial nucleosides. The infarct size in the 3 groups was not significantly different, independent of myocardial blood flow during ischemia.
CONCLUSIONS: Preconditioning or postconditioning with erythro-9 (2-hydroxy-3-nonyl)-adenine/p-nitrobenzylthioinosine significantly reduced the incidence of ventricular fibrillation and cardioversion and attenuated regional contractile dysfunction mediated by postmyocardial infarction reperfusion injury. It is concluded that p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 played a major role in these events.
Authors:
Anwar Saad Abd-Elfattah; Hamdy Aly; Scott Hanan; Andrew S Wechsler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-11
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  144     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-19     Completed Date:  2012-09-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  250-5     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Affiliation:
Division of Cardiothoracic Surgery, Department of Surgery, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0068, USA. aabdelfattah@mcvh-vcu.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Deaminase Inhibitors / pharmacology*
Adenosine Triphosphate / metabolism
Analysis of Variance
Animals
Coronary Circulation
Dogs
Equilibrative Nucleoside Transporter 1 / pharmacology*
Ischemic Preconditioning / methods*
Least-Squares Analysis
Myocardial Contraction / drug effects
Myocardial Infarction / metabolism,  physiopathology
Myocardial Reperfusion Injury / metabolism,  physiopathology,  prevention & control*
Myocardial Stunning / metabolism,  physiopathology,  prevention & control*
Thioinosine / analogs & derivatives*,  pharmacology
Ventricular Fibrillation / physiopathology,  prevention & control*
Grant Support
ID/Acronym/Agency:
R01 HL05-1090/HL/NHLBI NIH HHS; R01 HL051090-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adenosine Deaminase Inhibitors; 0/Equilibrative Nucleoside Transporter 1; 38048-32-7/4-nitrobenzylthioinosine; 56-65-5/Adenosine Triphosphate; 574-25-4/Thioinosine
Comments/Corrections

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