Number 23, 2004
Hibernation preconditioning

Metabolic cardioprotection in patients undergoing revascularization

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P. Meurin, T. Hénane
Centre de rééducation cardiaque de la Brie, Villetaneuse St Denis, France
Correspondence: T. Hénane, 192 av. Charles de Gaulle, 92200 Neuilly sur Seine, France. E-mail: thierry.henane@fr.netgrs.com

Introduction
The rationale of the manipulation of cardiac metabolism for the effective treatment of ischemic heart disease is now well demonstrated [1]. Trimetazidine (Vastarel MR) is the first twice-daily 3-ketoacyl coenzyme A thiolase (3-KAT) inhibitor to become available for clinical use worldwide. It acts by switching cardiac metabolism away from fatty acids to glucose oxidation, secondary to the selective inhibition of the mitochondrial enzyme, 3-KAT [2]. This novel and innovative approach proved efficient in relieving the symptoms of angina and improving exercise performance in various subsets of patients with coronary disease [3], while being free of any hemodynamic impact [4].
In patients undergoing a revascularization procedure, myocardial damage during the intervention is an important determinant of clinical outcome [5]. This article aims to show how the metabolic effect of trimetazidine can translate into cardioprotective benefits for patients who are referred for a revascularization procedure and in whom it is crucial to limit reperfusion damage.

Cardioprotective effect of trimetazidine during percutaneous transluminal coronary angioplasty
As a result of its experimentally demonstrated anti-ischemic properties [6], the efficacy and acceptability of trimetazidine were tested in clinical settings in patients with coronary disease who were undergoing percutaneous transluminal coronary angioplasty (PTCA). Trimetazidine was given before or after PTCA. The main clinical findings are summarized in Table I.

Table I. Clinical trials of trimetazidine in percutaneous transluminal coronary angioplasty: (Adapted from Marzilli [6], with permission.)

Cardioprotective effect of trimetazidine during coronary artery bypass grafting surgery
A double-blind, randomized, placebo-controlled study was carried out in Turkey to evaluate the anti-ischemic benefits of trimetazidine in 30 patients [10]. Vastarel was given orally for 3 weeks before a coronary artery bypass grafting (CABG) procedure. Plasma concentrations of the highly sensitive cardiac marker, troponin T, were measured 5min after the bypass operation, at 12, 24, and 48h postoperatively. As shown in Figure 2, troponin T concentrations in the trimetazidine group were significantly reduced in comparison with those in the placebo group, reflecting the cardioprotection triggered by the metabolic effect of trimetazidine. These results confirm previous data obtained in patients undergoing elective CABG in two or three vessels [11]. They were given a 3-week pretreatment with oral trimetazidine, then trimetazidine was added to the cardioplegic solution. Ventricular function was improved by the drug as shown by the stroke work index. Metabolic measurements showed a less important increase in malondialdehyde concentrations after trimetazidine (P=0.01).

Conclusion
Optimizing the energy metabolism of the heart under ischemic conditions such as those encountered during a revascularization procedure (PTCA or CABG surgery) is a novel and effective approach to protect the myocardium from the deleterious consequences of ischemia-reperfusion injury. The use of metabolically active agents, such as trimetazidine (Vastarel MR), to switch energy substrate preference from fatty acid oxidation to glucose oxidation, secondary to the inhibition of the 3-KAT enzyme, improves the production and utilization of energy at the cellular level. This metabolic effect translates into clinical benefits that are reflected by a delayed ischemic threshold or an improved ventricular function in patients undergoing bypass surgery or angioplasty. Promising clinical findings suggest that trimetazidine, the first 3-KAT inhibitor, is a treatment of choice before any intervention. ▪

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REFERENCES

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