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Effects of Trimetazidine on Metabolic and Functional Recovery of Postischemic Rat Hearts

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Abstract

The objective of this study was to test the hypothesis that the beneficial effect of trimetazidine during reflow of ischemic hearts is mediated by energy sparing and ATP pool preservation during ischemia. Isolated rat hearts (controls and rats treated with 10−6 M trimetazidine, n = 17 per group) underwent the following protocol: baseline perfusion at normal coronary flow (20 minutes), low-flow ischemia at 10% flow (60 minutes), and reflow (20 minutes). We measured contractile function, O2 uptake, lactate release, venous pH and PCO2, and the tissue content of high-energy phosphates and their metabolites. During baseline, trimetazidine induced higher venous pH and lower PCO2 without influencing performance and metabolism. During low-flow ischemia, trimetazidine reduced myocardial performance (P = 0.04) and ATP turnover (P = 0.02). During reflow, trimetazidine improved performance (91 ± 6% versus. 55 ± 6% of baseline), prevented the development of diastolic contracture and coronary resistance, and reduced myocardial depletion of adenine nucleotides and purines. ATP turnover during low-flow ischemia was inversely related to recovery of the rate-pressure product (P = 0.002), end-diastolic pressure (P = 0.007), and perfusion pressure (P = 0.05). We conclude that trimetazidine-induced protection of ischemic-reperfused hearts is also mediated by energy sparing during ischemia, which presumably preserves the ATP pool during reflow.

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Authors and Affiliations

  1. Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Milano, Italy

    Sonia Allibardi, Vittoria Margonato, Gabriella Neri & Michele Samaja

  2. Istituto Scientifico San Raffaele, Italy

    Sergio L. Chierchia & Giacomo Dell’Antonio

  3. Cattedra di Fisiologia, Università degli Studi di Brescia, Italy

    Giampiero Merati

Authors
  1. Sonia Allibardi
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  2. Sergio L. Chierchia
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  3. Vittoria Margonato
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  4. Giampiero Merati
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  5. Gabriella Neri
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  6. Giacomo Dell’Antonio
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  7. Michele Samaja
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Allibardi, S., Chierchia, S.L., Margonato, V. et al. Effects of Trimetazidine on Metabolic and Functional Recovery of Postischemic Rat Hearts. Cardiovasc Drugs Ther 12, 543–549 (1998). https://doi.org/10.1023/A:1007731219206

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  • DOI: https://doi.org/10.1023/A:1007731219206

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