Effects of trimetazidine on metabolic and functional recovery of postischemic rat hearts

Sonia Allibardi, Sergio L. Chierchia, Vittoria Margonato, Giampiero Merati, Gabriella Neri, Giacomof Dell'Antonio, Michele Samaja

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)543-549
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume12
Issue number6
DOIs
Publication statusPublished - 1998

Keywords

  • ATP metabolism
  • Bioenergetics
  • Low-flow ischemia
  • Reperfusion
  • Trimetazidine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)
  • Pharmacology

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