Prospective Observational Study of Trimetazidine Influence on Mitochondrial Metabolism in Human Heart Ventricle

Study Overview
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Brief Summary
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Trimetazidine (1-[2,3,4-trimethoxybenzyl] piperazine dihydrochloride) is a clinically effective antianginal agent. Despite these clinical successes, the understanding of trimetazidine's mechanism of action remains incomplete, particularly influence of trimetazidine on mitochondrial function in isolated human cardiomyocytes. The investigators will perform this study to seek possible differences in mitochondrial respiration related to standard preoperative enrolled trimetazidine therapy.

Detailed Description
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Background: Different types of medication are used for treatment of ischemic heart disease. One of recently developed drugs is trimetazidine. Although it clinical benefits are clear, mechanism by which this occurs is as yet undefined. In few animal studies authors try to define what effects trimetazidine has on both fatty acid and glucose metabolism in heart. Data collected from human cardiomyocytes are rare. Available data suggest that trimetazidine may act as a potent inhibitor of beta oxidation, with no significant effect on glucose oxidation. Objective: Primary objective: collection of mitochondrial respiration data using human heart ventricular samples. Secondary objective: define possible differences in mitochondrial respiration depending on preoperative trimetazidine usage. Methods: Regularly scheduled patients for coronary artery bypass grafting surgery who accept to participate in study will be enrolled in further protocol. Patients with inclusion criteria and without exclusion criteria will be enrolled in the study. At the end of operation, surgeon will take biopsy sample of left ventricle for mitochondrial function and metabolic activity analysis.

Official Title
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Myocardial Energetics as a Target for Treatment of Ischemic Heart Disease: A Translational Approach From Patient to Mitochondria

Conditions
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Coronary Artery Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with coronary artery disease who are candidates for coronary artery bypass graft (CABG) surgery. Exclusion Criteria: Emergency patients, patients who already had heart surgery, patients with acute coronary syndrome in last 2 months, patients with inability to understand patient information and informed consent.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Trimetazidine<br>Patients for coronary artery bypass grafting surgery who had preoperative trimetazidine usage in standard ischemic coronary disease therapy. | |
| Control<br>Patients for coronary artery bypass grafting surgery who had standard therapy for ischemic coronary disease without trimetazidine. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in rate of myocardial oxygen consumption expressed in pmolO2/min/units of citrate synthase activity. | Investigators will obtain left ventricular biopsy samples from patients suffering from ischemic heart disease. Samples will be prepared in the laboratory for the purpose of assessment of mitochondrial respiration. Using the specific substrates from either fatty acid or carbohydrate metabolic pathways will enable investigation of the effect of trimetazidine on cardiac tissue metabolism. | Within 24 hours after tissue biopsy |