Improvement of Long-Term Preservation of the Isolated Arrested Rat Heart By Trimetazidine: Effects on the Energy State and Mitochondrial Function

Kay, Laurence; Finelli, Caterina; Aussedat, J.; Guarnieri, Carlo; Rossi, A.

doi:10.1016/s0002-9149(99)80462-7

Cited by 28 publications

(9 citation statements)

References 5 publications

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“…How trimetazidine maintains a constant V3 level is not known. It may interfere with metabolism (Guarnieri & Muscari, 1993; Kay et al , 1995) and preserve cell energy (Lavanchy et al , 1987). Favouring the expression of the myosin V3 form, which has lower ATPase activity and utilizes less energy, trimetazidine would bring the cells either to a reduced activity state or to a ‘normoxic’metabolic switch (Demaison et al , 1995).…”

Section: Discussionmentioning

confidence: 99%

Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype

D'hahan

Taouil

Janmot

et al. 1998

British J Pharmacology

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1 In this study we investigated whether long-term trimetazidine (anti-ischaemic drug) therapy alters the ventricular myosin heavy chain (MHC) isoform composition in a model of cardiomyopathy. 2 MHC isoforms were analysed in the native state by electrophoresis in a pyrophosphate buer. Myosin isoform patterns were studied in cardiac muscle from cardiomyopathic hamsters (CMH) of the BIO 14 : 6 strain during the time course of the disease and compared with those of healthy golden hamsters (F1B). The correlation between myosin pro®le and Ca 2+ -activated ATPase activity was determined from 220 days. 3 At the stage of insuciency (350 days), CMH presented the most abnormal phenotype with 53% V1-24% V3 compared to 79% V1-7% V3 (P50.001), in F1B. Trimetazidine was administered to cardiomyopathic hamsters from the early stage of active disease (30 days) to the congestive stages (220 ± 350 days). Within 65 days, trimetazidine treatment, in CMH and F1B, reduced V1 to a low level (53% and 62%, respectively), which remained constant throughout the treatment. This level was similar to that in 220 and 350 days-old untreated-CMH. In sharp contrast, a standard calcium blocker, verapamil, administered to CMH in the same conditions resulted in a higher V1 (about 70%) and higher global myosin ATPase activity from 220 days. 4 Previous results in terms of hypertrophy and survival, compared to these results, suggest that verapamil and trimetazidine treatments reveal a disssociation between ventricular hypertrophy and isomyosin distribution. In addition, the shift in favour of V3 may not necessarily be an aggravating factor of the disease but an adaptative compensatory event.

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Section: Discussionmentioning

confidence: 99%

Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype

D'hahan

Taouil

Janmot

et al. 1998

British J Pharmacology

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“…The beneficial effect of this agent has been attributed to preservation of intracellular concentrations of phosphocreatine and ATP7 8 and reduction of cell acidosis,9 10 calcium overload10 and free-radical-induced injury caused by ischaemia 11. More importantly, trimetazidine affects myocardial substrate utilisation by inhibiting oxidative phosphorylation and shifting energy production from free fatty acids (FFAs) to glucose oxidation 12 13. This effect appears to be predominantly caused by a selective block of long-chain 3-ketoacyl-CoA thiolase activity, the last enzyme involved in ß-oxidation 14.…”

Section: Introductionmentioning

confidence: 99%

Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure

Fragasso

Salerno

Lattuada³

et al. 2011

Heart

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“…To date, numerous studies have reported that adding TMZ to the perfusion fluid of ischaemic rat hearts significantly improves the energy state of the myocardial cells, and limits the neutrophil infiltration and the consequent membrane damage [ 6, 7]. Our group’s previous report has also shown that although administration of TMZ does not provoke any significant alterations in limiting oxyradical production, it preserves the tGSH levels of the cell, probably by improving the energy status [ 18].…”

Section: Discussionmentioning

confidence: 99%

“…This study was undertaken to investigate the possible protective effects of pretreatment with such a new agent, trimetazidine (TMZ; 1‐[2,3,4‐trimethoxy‐benzyl] piperazine HCl), on the oxidant–anti‐oxidant balance in ethanol‐ and acetic acid‐induced colonic damage in rats. TMZ was chosen because of its various cytoprotective features (preserving cellular ATP levels, limiting intracellular acidosis and limiting inorganic phosphate, Na + and Ca 2+ accumulation) on ischaemic cardiac injury, although it was originally introduced only as an anti‐anginal compound [ 6, 7]. Through recent research on TMZ it was noted that these effects were independent of alterations in oxygen supply or demand, since neither systemic haemodynamics nor coronary blood flow were altered by the compound [ 8].…”

Section: Introductionmentioning

confidence: 99%

Effects of trimetazidine in ethanol‐ and acetic acid‐induced colitis: oxidant/anti‐oxidant status

et al. 1999

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There is overwhelming evidence in favour of a significant role of reactive oxygen metabolites (ROM) in the pathophysiology of inflammatory bowel disease (IBD) in man and in experimental animal models. This study was undertaken to investigate the possible protective effects of pretreatment with trimetazidine (TMZ) on the oxidant-anti-oxidant balance in ethanol- and acetic acid-induced colonic damage in rats. TMZ was chosen because of its various cytoprotective features (preserving cellular ATP levels, limiting intracellular acidosis and limiting inorganic phosphate, Na(+) and Ca(2+) accumulation) and anti-oxy characteristics which were previously reported. A total of 80 rats were randomized into eight major groups each consisting of 10 animals. Animals in groups 1, 2 and 3 served as models of ethanol-induced colitis (0.25 ml of 30% (v/v) ethanol), while group 4 served as their control. Animals in groups 5, 6 and 7 served as models of acetic acid-induced colitis (1 ml of 4% (v/v) acetic acid), while group 8 served as their control. TMZ was administered 5 mg/kg by intrarectal (i.r.) and intraperitoneal (i.p.) routes to groups 1, 2, 5 and 6. Intraperitoneal administration of TMZ was used in order to evaluate its systemic effect while i.r. administration was used to determine its local effect. After decapitation, colon mucosa samples were obtained and evaluated macroscopically and microscopically. Myeloperoxidase (MPO) activities as markers for inflammation, malondialdehyde (MDA) levels as markers for oxidant stress and reduced glutathione (GSH) and oxidized glutathione (GSSG) levels as markers for anti-oxidant status were determined. Acute colitis was observed in macroscopic and microscopic evaluation in ethanol- and acetic acid-administered groups compared with controls (P = 0.000). The macroscopic and microscopic scores in colitis groups were correlated with MPO activities (r = 0.5365, P = 0.000 and r = 0.5499, P = 0.000, respectively). MDA and GSSG levels in the acetic acid-induced colitis group were higher compared with ethanol-induced colitis group (P < 0.008 and P < 0.005, respectively), while GSH levels were significantly lower (P < 0.05). While TMZ pretreatment did not improve the oxidant state, it preserved the GSH levels significantly (P < 0.05). In conclusion, ethanol- and acetic acid-induced colitis models are appropriate experimental colitis models which in many ways manifest the characteristics seen in tissue injury related to colitis in humans. Of these two, the acetic acid-induced colitis model proved more suitable than the ethanol model for investigating the alterations in long-term and in more severe tissue injury. While TMZ pretreatment via i.p. or i.r. route did not improve the oxidative-inflammative state in either of these models, it did contribute significantly to the preservation of the anti-oxidant pool via the conservation of intracellular GSH levels. This conserving effect of TMZ was substantially more pronounced in the i.p. route compared with the i.r. route. Based on our results, we concl...

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Improvement of Long-Term Preservation of the Isolated Arrested Rat Heart By Trimetazidine: Effects on the Energy State and Mitochondrial Function

Cited by 28 publications

References 5 publications

Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype

Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype

Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure

Effects of trimetazidine in ethanol‐ and acetic acid‐induced colitis: oxidant/anti‐oxidant status

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