Myocardial infarct size-limiting and anti-arrhythmic effects of mildronate orotate in the rat heart

Reinis Vilskersts, Edgars Liepinsh, Janis Kuka, Helena Cirule, Maris Veveris, Ivars Kalvinsh, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Purpose: Mildronate and orotic acid act as modulators of energy metabolism and are considered as cardioprotective agents. This study was performed to compare the cardioprotective effects of mildronate, orotic acid and mildronate orotate. Methods: Male Wistar rats received mildronate, orotic acid or mildronate orotate for 14 days. The isolated rat heart infarction and isoproterenol-induced ischemia models were used to test the cardioprotective effects of compounds studied. Experimental arrhythmias were induced by the ligation of the left anterior descending coronary artery for 10 min with subsequent reperfusion or by administration of calcium chloride or aconitine at arrhythmogenic doses. Results: The data obtained showed a statistically significant decrease of necrotic area in 25% of infarcted rat hearts after 14 days of treatment with mildronate and orotic acid, whereas mildronate orotate decreased the infarct size by 50%. Moreover, we found that the administration of mildronate and its orotate salt decreased the duration and incidence of arrhythmias in experimental arrhythmia models. Conclusions: The study provides experimental evidence that the combination of orotic acid and mildronate possesses additive pharmacological effects and that mildronate orotate might be considered as a powerful therapeutic agent facilitating recovery from ischemia-reperfusion injury.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume23
Issue number4
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

Keywords*

  • Experimental arrhythmia
  • Metabolic therapy
  • Mildronate
  • Myocardial nfarction
  • Orotate
  • Rats

Field of Science*

  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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