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This Article Full Text Full Text (PDF) All Versions of this Article: 91/3/591    most recent expphysiol.2005.032615v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meng, D. Articles by Zhang, J.-N. Search for Related Content PubMed PubMed Citation Articles by Meng, D. Articles by Zhang, J.-N. Related Collections Cardiovascular control

¹ Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China² Research Institute of Cardiovascular Disease, First Affiliated Hospital and Human Functional Genetics Laboratory of Jiangsu province of Nanjing Medical University, Nanjing, 210029, China

Dysregulation of intracellular Ca²⁺ homeostasis plays an important role in mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve intracellular Ca²⁺ handling in myocardial injury of rats. The control group received saline only (10 ml kg^–1 day^–1, I.P.) for 7 days. In a second group, isoprenaline (ISO; 5 mg kg^–1 day^–1, S.C.) was administered to rats for 2 days to induce an acute injury of the myocardium. In a third group, treatment with TMZ (10 mg kg^–1 day^–1, I.P.) was initiated 1 day before ISO administration and continued for 7 days (n= 7 rats in each group). Histopathological evaluation showed that TMZ prevented ISO-induced myocardial damage. TMZ preserved the ATP levels and decreased the maleic dialdehyde (MDA) content in the hearts compared with ISO-treated rats. The diastolic [Ca²⁺]_i measured by loading with fura-2 AM in isolated cardiomyocytes was increased significantly in ISO-treated rats compared to the control animals. TMZ prevented the rise of diastolic [Ca²⁺]_i and the depression of caffeine-induced Ca²⁺ transients caused by ISO administration. The reduction in sarcoplasmic reticulum (SR) Ca²⁺ content in the heart cells and in cardiac SR Ca²⁺-ATPase activity in ISO-treated rats was abolished by TMZ, although there were no differences in SR Ca²⁺-ATPase protein levels between the control, ISO and ISO + 7 mz-treated rats. In addition, TMZ prevented the reduction in sarcolemmal L-type Ca²⁺ current density in the heart cells induced by ISO treatment. These results demonstrate that the treatment of rats with TMZ inhibited the increase of diastolic [Ca²⁺]_i and prevented the decrease of SR Ca²⁺ content, SR Ca²⁺-ATPase activity and L-type Ca²⁺ current density in cardiomyocytes in ISO-mediated myocardial injury of rats. These changes in Ca²⁺ handling could help to explain the favourable action of TMZ in myocardial injury.

(Received 17 October 2005; accepted after revision 3 February 2006; first published online 9 February 2006)
Corresponding author D. Meng: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. Email: dmeng{at}sibs.ac.cn

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				Corrigendum. Exp Physiol, July 1, 2006; 91(4): 799 - 799. [Full Text] [PDF]