Long-term therapy with trimetazidine in cardiomyopathic Syrian hamster BIO 14:6

D'hahan, Nathalie; Taouil, Karima; Dassouli, Abdelilah; Morel, Jean E.

doi:10.1016/s0014-2999(97)83042-7

Cited by 30 publications

(27 citation statements)

References 34 publications

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“…Long-term oral treatment was more efficient than the Ca 2+ blocker verapamil [25]. Trimetazidine increased the median survival time by 57%, cardiac hypertrophy was reduced and the total Ca 2+ level reverted to that of normal hamsters [25]. This finding would be in accordance with studies showing that cardiomyopathic hamsters exhibit a reduced pyruvate dehydrogenase activity [28].…”

Section: Trimetazidinesupporting

confidence: 83%

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The Use of Partial Fatty Acid Oxidation Inhibitors for Metabolic Therapy of Angina Pectoris and Heart Failure

Rupp

Zarain‐Herzberg

Maisch

2002

Herz

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Partial fatty acid oxidation inhibitors have raised great interest since they are expected to counteract a dysregulated gene expression of hypertrophied cardiocytes. Some of these compounds have been developed for treating non-insulin-dependent diabetes mellitus and stable angina pectoris. A shift from fatty acid oxidation to glucose oxidation leads to a reduced gluconeogenesis and improved economy of cardiac work. An increased glucose oxidation can be achieved with the following enzyme inhibitors: etomoxir, oxfenicine, methyl palmoxirate, S-15176, metoprolol, amiodarone, perhexiline (carnitine palmitoyltransferase-1); aminocarnitine, perhexiline (carnitine palmitoyltransferase-2); hydrazonopropionic acid (carnitine-acylcarnitine translocase); MET-88 (gamma-butyrobetaine hydroxylase); 4-bromocrotonic acid, trimetazidine, possibly ranolazine (thiolases); hypoglycin (butyryl-CoA dehydrogenase); dichloroacetate (pyruvate dehydrogenase kinase). CLINICAL TRIALS with trimetazidine and ranolazine showed that this shift in substrate oxidation has an antianginal action. Etomoxir and MET-88 improved the function of overloaded hearts by increasing the density of the Ca(2+) pump of sarcoplasmic reticulum (SERCA2). The promoters of SERCA2 and alpha-myosin heavy-chain exhibit sequences which are expected to respond to transcription factors responsive to glucose metabolites and/or peroxisome proliferator-responsive element (PPAR) agonists. Further progress in elucidating novel compounds which upregulate SERCA2 expression is closely linked to the characterization of regulatory sequences of the SERCA2 promoter.

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Section: Trimetazidinesupporting

confidence: 83%

“…Trimetazidine exhibited also a protective action in cardiomyopathic hamsters. Long-term oral treatment was more efficient than the Ca 2+ blocker verapamil [25]. Trimetazidine increased the median survival time by 57%, cardiac hypertrophy was reduced and the total Ca 2+ level reverted to that of normal hamsters [25].…”

Section: Trimetazidinementioning

confidence: 96%

The Use of Partial Fatty Acid Oxidation Inhibitors for Metabolic Therapy of Angina Pectoris and Heart Failure

Rupp

Zarain‐Herzberg

Maisch

2002

Herz

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“…Myocardial homogenates from cardiomyopathic Syrian hamster have a decreased capacity for mitochondrial oxidative metabolism (2,25), which is due to a defect in interfibrillar mitochondria (IFM) (21). Furthermore, these animals have a greater susceptibility to stress-induced MPT and respond to nutritional and metabolic therapies (4,10,11,21). We administered DHA and EPA at a clinically relevant dose (2.1% of energy intake; equivalent to ϳ4.7 g/day in humans).…”

mentioning

confidence: 99%

Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival

Galvão

Khairallah

Dabkowski

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Mitochondrial dysfunction in heart failure includes greater susceptibility to mitochondrial permeability transition (MPT), which may worsen cardiac function and decrease survival. Treatment with a mixture of the n3 polyunsaturated fatty acids (n3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is beneficial in heart failure patients and increases resistance to MPT in animal models. We assessed whether DHA and EPA have similar effects when given individually, and whether they prolong survival in heart failure. Male δ-sarcoglycan null cardiomyopathic hamsters were untreated or given either DHA, EPA, or a 1:1 mixture of DHA + EPA at 2.1% of energy intake. Treatment did not prolong survival: mean survival was 298 ± 15 days in untreated hamsters and 335 ± 17, 328 ± 14, and 311 ± 15 days with DHA, EPA, and DHA + EPA, respectively (n = 27-32/group). A subgroup of cardiomyopathic hamsters treated for 26 wk had impaired left ventricular function and increased cardiomyocyte apoptosis compared with normal hamsters, which was unaffected by n3 PUFA treatment. Evaluation of oxidative phosphorylation in isolated subsarcolemmal and interfibrillar mitochondria with substrates for complex I or II showed no effect of n3 PUFA treatment. On the other hand, interfibrillar mitochondria from cardiomyopathic hamsters were significantly more sensitive to Ca(2+)-induced MPT, which was completely normalized by treatment with DHA and partially corrected by EPA. In conclusion, treatment with DHA or EPA normalizes Ca(2+)-induced MPT in cardiomyopathic hamsters but does not prolong survival or improve cardiac function. This suggest that greater susceptibility to MPT is not a contributor to cardiac pathology and poor survival in heart failure.

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“…The cardiomyopathy is apparent at Ϸ10 weeks of age and becomes clinically apparent at 17 weeks of age. [13][14][15][16][17][18][19][20] Therefore, BIO 53.58 hamsters provide a good model of dilated cardiomyopathy. We used 4-week-old BIO 53.58 hamster cardiomyocytes as transplant donors.…”

Section: Discussionmentioning

confidence: 99%

Heart Cell Transplantation Improves Heart Function in Dilated Cardiomyopathic Hamsters

Yoo

Li²,

Weisel³

et al. 2000

Circulation

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Background-Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium.This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters. Methods and Results-Ventricular heart cells were isolated from 4-week-old BIO 53.58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4ϫ10 6 cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, nϭ12 each). Sham-operated hamsters (nϭ12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater (PϽ0.001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915Ϯ253 versus control 453Ϯ120 and sham 530Ϯ187 mm Hg/s, PϽ0.001, balloon volume of 15 L). No differences in ventricular function were found between control and sham-operated hamsters. Conclusions-The

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Long-term therapy with trimetazidine in cardiomyopathic Syrian hamster BIO 14:6

Cited by 30 publications

References 34 publications

The Use of Partial Fatty Acid Oxidation Inhibitors for Metabolic Therapy of Angina Pectoris and Heart Failure

The Use of Partial Fatty Acid Oxidation Inhibitors for Metabolic Therapy of Angina Pectoris and Heart Failure

Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival

Heart Cell Transplantation Improves Heart Function in Dilated Cardiomyopathic Hamsters

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