| Modulation of the nitric oxide metabolism overcomes the unresponsiveness of the diabetic human myocardium to protection against ischemic injury. | |
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MedLine Citation:
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PMID: 20869072 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: We have demonstrated that diabetic human myocardium cannot be protected by ischemic preconditioning (IP) and identified a dysfunction of the mitochondria as the cause of the defect. Here we have investigated whether modulation of the nitric oxide (NO) metabolism can overcome the unresponsiveness of the diabetic myocardium to cardioprotection. METHODS: Myocardial slices (30-40 mg) obtained from the right atrial appendage of patients with diabetes undergoing elective cardiac surgery were randomized to the following protocol (n = 6/group): NO donor SNAP (100 μM), nonselective nitric oxide synthase (NOS) inhibitor L-NAME (100 μM), and selective neuronal NOS (nNOS) inhibitor TRIM (100 μM) for 20 min prior to 90 min ischemia followed by 120 min reoxygenation (37°C). Some preparations were subjected to ischemic/reoxygenation alone or to IP (5 min ischemia/5 min reoxygenation) to act as control. Tissue injury was assessed by creatine kinase (CK) released (IU/mg wet wt), and cell necrosis and apoptosis by propidium iodide and TUNEL (% of aerobic control). RESULTS: IP did not decrease CK release, cell necrosis or apoptosis in diabetic myocardium. However, NO donor SNAP, the nonspecific NOS inhibitor L-NAME, and the specific nNOS inhibitor TRIM significantly reduced CK leakage, cell necrosis, and apoptosis in diabetic myocardium. CONCLUSIONS: These results demonstrate that both the provision of exogenous NO and the suppression of endogenous NO production result in potent protection of diabetic human myocardium overcoming the unresponsiveness of these tissues to cardioprotective therapies. |
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Authors:
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Anupama Barua; Nicholas B Standen; Manuel Galiñanes |
Publication Detail:
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Type: Journal Article Date: 2010-08-15 |
Journal Detail:
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Title: The Journal of surgical research Volume: 171 ISSN: 1095-8673 ISO Abbreviation: J. Surg. Res. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: United States |
Other Details:
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Languages: eng Pagination: 452-6 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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