Journal article
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
The Journal of thoracic and cardiovascular surgery, v 144(1), pp 250-255
01 Jul 2012
PMID: 22329983
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 mu M of erythro-9 (2-hydroxy-3-nonyl)-adenine and 25 mu M 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. (J Thorac Cardiovasc Surg 2012;144:250-5)
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Details
- Title
- 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
- Creators
- Anwar Saad Abd-Elfattah - Virginia Commonwealth University Medical CenterHamdy Aly - Ain Shams University Faculty of MedicineScott Hanan - Virginia Commonwealth University Medical CenterAndrew S. Wechsler - Drexel University
- Publication Details
- The Journal of thoracic and cardiovascular surgery, v 144(1), pp 250-255
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- R01 HL05 1090 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL051090 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000305412200041
- Scopus ID
- 2-s2.0-84862596156
- Other Identifier
- 991019168321304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Respiratory System
- Surgery