Ionic and metabolic imbalance as potential factors of ischemia reperfusion injury

Banani, H El; Bernard, Monique; Cozzone, Patrick J.; James, Françoise; Feuvray, D.

doi:10.1016/s0002-9149(98)00534-7

Cited by 11 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In other words, postischemic function of hypertrophied hearts was normalized by trimetazidine. Beneficial effects of trimetazidine during isch- (Rahman et al, 1989;Guarnieri and Muscari, 1993;Boucher et al, 1994;Allibardi et al, 1998;El Banani et al, 1998 and clinical (Anonymous, 2000;Steg et al, 2001) studies. That significant functional improvement after ischemia was only observed in hypertrophied hearts suggests that trimetazidine is especially beneficial to the hypertrophied heart.…”

Section: Discussionmentioning

confidence: 99%

Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts

Saeedi

Grist²,

Wambolt³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The fraction of glucose passing through glycolysis that is oxidized is low in hypertrophied hearts, a pattern of glucose use associated with poor postischemic contractile function. We tested the hypothesis that trimetazidine, a partial 3-ketoacyl coenzyme A thiolase inhibitor, would stimulate glucose oxidation and, thereby, improve fractional glucose oxidation and postischemic function of hypertrophied hearts. Function, glycolysis, and oxidation of glucose, lactate, and palmitate were measured before and after global no-flow ischemia in isolated working hearts from sham-operated (control) and aortic-constricted (hypertrophied) male Sprague-Dawley rats in the presence or absence of 1 M trimetazidine. Heart function was significantly improved by trimetazidine after ischemia, but only in hypertrophied hearts, with function improving to values in untreated control hearts. This effect occurred in association with relatively minor changes in oxidative metabolism. However, trimetazidine reduced glycolysis by ϳ30% but did so only in hypertrophied hearts, an unexpected novel action of this agent that resulted in a larger fractional oxidation of glucose, effectively normalizing it in hypertrophied hearts. Thus, trimetazidine normalizes postischemic function and fractional glucose oxidation in hypertrophied hearts, mainly by reducing glycolysis. These data extend the potential usefulness of trimetazidine and provide support for its use as a means to improve postischemic function of pressure overload hypertrophied hearts.

show abstract

Section: Discussionmentioning

confidence: 99%

Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts

Saeedi

Grist²,

Wambolt³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Glycolytic H + production would otherwise lead to increased Na + /H + exchange activity [35], increased intracellular Na + [36], increased intracellular Ca 2+ [37], mitochondrial dysfunction [38] and myocardial injury [37]. Consistent with this hypothesis, trimetazidine has been shown to decrease ischaemic H + production [32], decrease ischaemic Na + and Ca 2+ accumulation [39], protect ischaemic mitochondrial function [38] and preserve ischaemic ATP levels [40].…”

Section: Mechanism Of Actionmentioning

confidence: 97%

“…In the 6 week crossover study comparing trimetazidine to nifedipine in 39 Trimetazidine, at the standard dose of 20 mg t.i.d., has no effect on haematological or biochemical parameters [45,52].…”

Section: Adverse Effectsmentioning

confidence: 99%

Trimetazidine for stable angina pectoris

Cross

2001

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Stable angina pectoris, a symptom of coronary heart disease (CHD), manifests as stress-induced ischaemic episodes resulting in severe chest pain. Therapeutic aims are to improve quality of life by decreasing anginal attacks and to prevent myocardial infarction (MI) and death. Current anginal medications include beta-blockers and calcium antagonists, which decrease ischaemic severity by reducing cardiac workload, and nitrates, which increase coronary blood flow. A new therapeutic approach is the use of metabolic agents, such as trimetazidine, which are cytoprotective during ischaemia. Results of several clinical trials demonstrated that trimetazidine, at the standard dose of 20 mg t.i.d., increased exercise capacity, decreased anginal incidence and decreased left-ventricular (LV) dysfunction compared to placebo. Trimetazidine was also as effective as propranolol (120 - 160 mg/day) and nifedipine (40 mg/day) in decreasing anginal episodes and improving exercise parameters. Trimetazidine improved anginal frequency and symptoms in patients in which treatment with diltiazem, nifedipine, propranolol, pindolol, oxprenolol or long-acting nitrates had failed. Trimetazidine was also more effective than isosorbide dinitrate (30 mg/day) as an adjunct to propranolol. Despite efficacy being equivalent to that of beta-blockers and calcium antagonists, trimetazidine does not depress cardiac function and, correspondingly, is not contraindicated in any condition. Adverse effects of trimetazidine are mild and infrequent. In summary, clinical data indicate that trimetazidine is a safe, effective treatment for the symptoms of stable angina pectoris when used either as a monotherapy or an adjunctive therapy. Longer-term trials are necessary to determine whether trimetazidine will be effective in reducing rates of mortality and MI.

show abstract

“…The inhibitory effect of TMZ on fatty acid oxidation was further supported in ischemia‐reperfusion studies in rat hearts. Ischemia‐induced increase in acyl carnitine levels—an indicator of fatty acid utilization—was significantly decreased with acute TMZ treatment along with a lower reduction in the intracellular pH during ischemia (El Banani et al 1998). Also, TMZ increased glucose utilization in dogs undergoing open‐chest left anterior descending coronary artery (LAD) ligation, as imaged by quantitative positron emission tomography (PET) (Mody et al 1998).…”

Section: Pharmacological Effectsmentioning

confidence: 99%

Trimetazidine Revisited: A Comprehensive Review of the Pharmacological Effects and Analytical Techniques for the Determination of Trimetazidine

Onay-Beşi̇kçi̇

Özkan

2008

Cardiovascular Therapeutics

View full text Add to dashboard Cite

Trimetazidine (TMZ) is an effective and well‐tolerated antianginal drug that possesses protective properties against ischemia‐induced heart injury. Growing interest in metabolic modulation in recent years urged an up‐to‐date review of the literature on TMZ. This review consists of two major sections: (1) comprehensive and critical information about the pharmacological effects, mechanism of action, pharmacokinetics, side effects, and current usage of TMZ, and (2) developments in analytical techniques for the determination of the drug in raw material, pharmaceutical dosage forms, and biological samples.

show abstract

Ionic and metabolic imbalance as potential factors of ischemia reperfusion injury

Cited by 11 publications

References 15 publications

Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts

Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts

Trimetazidine for stable angina pectoris

Trimetazidine Revisited: A Comprehensive Review of the Pharmacological Effects and Analytical Techniques for the Determination of Trimetazidine

Contact Info

Product

Resources

About