| Pre-treatment with trimetazidine increases sarcolemmal mechanical resistance in reoxygenated myocytes. | |
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MedLine Citation:
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PMID: 8881519 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Cytoskeletal and sarcolemmal fragility secondary to anoxia may contribute to sarcolemmal rupture and cell death during reoxygenation of cardiomyocytes. This study investigated the influence of trimetazidine (TMZ), a drug with effects on lipid metabolism and cell membranes, on reoxygenation-induced sarcolemmal rupture. METHODS: Isolated adult rat myocytes were submitted to 60 min of metabolic inhibition and 5 min of hypo-osmotic reoxygenation to simulate reperfusion edema in situ. Cells were allocated to 3 groups of treatment: in one group, TMZ 100 mumol/l was added to both the metabolic inhibition and reoxygenation buffers (group TMZ); another group was submitted to the same treatment but cells had previously been incubated with TMZ 100 mumol/l for 3 h (group TMZ-Pre); a control group underwent metabolic inhibition and hypo-osmotic reoxygenation without any treatment. Cell morphology was monitored throughout the experiment and sarcolemmal integrity was assessed by quantification of LDH activity and trypan blue exclusion test. RESULTS: After 60 min of metabolic inhibition most cells (83.1 +/- 2%) presented rigor contracture without between-group differences. Reoxygenation resulted in hypercontracture of 84.2 +/- 2.3, 91.2 +/- 1.4 and 84.1 +/- 2.1% of cells in TMZ, TMZ-Pre and control groups, P = NS. The trypan blue exclusion test revealed a higher proportion of cells with sarcolemmal integrity in TMZ and TMZ-Pre groups than in controls (12.7 +/- 2.0, 10.0 +/- 1.5 and 6.3 +/- 0.8%, respectively, P = 0.002). No between-group differences in LDH activity in the extracellular medium were observed at the onset or at the end of metabolic inhibition. However, LDH release was significantly lower (P = 0.002) in the TMZ-Pre group (1.6 +/- 0.1 IU/1000 cells) than in the TMZ and control groups (1.9 +/- 0.2 and 2.2 +/- 0.1 IU/1000 cells). CONCLUSION: Preincubation of cardiomyocytes with TMZ does not prevent rigor contracture induced by metabolic inhibition or hypercontracture during subsequent reoxygenation, but does improve sarcolemmal resistance to reoxygenation-induced mechanical stress. This could help to explain the beneficial effect of TMZ on infarct size. |
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Authors:
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M Ruiz-Meana; D Garcia-Dorado; M Juliá; M A González; J Inserte; J Soler-Soler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cardiovascular research Volume: 32 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 1996 Sep |
Date Detail:
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Created Date: 1996-12-16 Completed Date: 1996-12-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 587-92 Citation Subset: IM; S |
Affiliation:
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Servicio de Cardiología, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Heart / drug effects Male Myocardial Ischemia / metabolism* Myocardial Reperfusion Injury / prevention & control Myocardium / metabolism* Osmotic Pressure Oxygen / metabolism* Rats Rats, Sprague-Dawley Sarcolemma / drug effects, metabolism* Stress, Mechanical Trimetazidine / pharmacology* Video Recording |
| Chemical | |
Reg. No./Substance:
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5011-34-7/Trimetazidine; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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