This Article Figures Only Full Text Full Text (PDF) 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 Takaseya, T. Articles by Aoyagi, S. Search for Related Content PubMed PubMed Citation Articles by Takaseya, T. Articles by Aoyagi, S.

Mechanical unloading improves intracellular Ca²⁺ regulation in rats with doxorubicin-induced cardiomyopathy

Tohru Takaseya, MD^*,*, Masaru Ishimatsu, MD, PhD, Eiki Tayama, MD, PhD^*, Akinori Nishi, MD, PhD, Takashi Akasu, MD, PhD and Shigeaki Aoyagi, MD, PhD^*

^* Department of Surgery, Kurume University School of Medicine, Kurume, Japan
Department of Physiology, Kurume University School of Medicine, Kurume, Japan

Manuscript received May 28, 2004; accepted August 23, 2004.

^* Reprint requests and correspondence: Dr. Tohru Takaseya, Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan (Email: takaseya{at}med.kurume-u.ac.jp).

OBJECTIVES: We sought to assess whether mechanical unloading has beneficial effects on cardiomyocytes from doxorubicin-induced cardiomyopathy in rats.

BACKGROUND: Mechanical unloading by a left ventricular assist device (LVAD) improves the cardiac function of terminal heart failure in humans. However, previous animal studies have failed to demonstrate beneficial effects of mechanical unloading in the myocardium.

METHODS: The effects of mechanical unloading by heterotopic abdominal heart transplantation were evaluated in the myocardium from doxorubicin-treated rats by analyzing the intracellular free calcium level ([Ca²⁺]_i) and the levels of intracellular Ca²⁺-regulatory proteins.

RESULTS: In doxorubicin-treated rats, the duration of cell shortening and [Ca²⁺]_i transients in cardiomyocytes was prolonged (432 ± 28.2% of control in 50% relaxation time; 184 ± 10.5% of control in [Ca²⁺]_i 50% decay time). Such prolonged time courses significantly recovered after mechanical unloading (114 ± 10.4% of control in 50% relaxation time; 114 ± 5.8% of control in 50% decay time). These effects were accompanied by an increase in sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a) protein levels (0.97 ± 0.05 in unloaded hearts vs. 0.41± 0.09 in non-unloaded hearts). The levels of other intracellular Ca²⁺-regulatory proteins (phospholamban and ryanodine receptor) were not altered after mechanical unloading in doxorubicin-treated hearts. These parameters in unloaded hearts without doxorubicin treatment were similar to normal hearts.

CONCLUSIONS: Mechanical unloading increases functional sarcoplasmic reticulum Ca²⁺ ATPase and improves [Ca²⁺]_i handling and contractility in rats with doxorubicin-induced cardiomyopathy. These beneficial effects of mechanical unloading were not observed in normal hearts.

Abbreviations and Acronyms   [Ca 2+]i = intracellular free Ca2+ level   GAPDH = glyceraldehyde-3-phosphate dehydrogenase   LV = left ventricle/ventricular   LVAD = left ventricular assist device   PLB = phospholamban   RT-PCR = reverse transcription-polymerase chain reaction   RyR = ryanodine receptor   SERCA2a = sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase)   SR = sarcoplasmic reticulum

This article has been cited by other articles:

				M. Pu, Z. Gao, X. Zhang, D. Liao, D. K. Pu, T. Brennan, and W. R. Davidson Jr. Impact of mitral regurgitation on left ventricular anatomic and molecular remodeling and systolic function: implication for outcome Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1727 - H1732. [Abstract] [Full Text] [PDF]

				J. Wang, A. Marui, T. Ikeda, and M. Komeda Partial left ventricular unloading reverses contractile dysfunction and helps recover gene expressions in failing rat hearts Interactive CardioVascular and Thoracic Surgery, February 1, 2008; 7(1): 27 - 31. [Abstract] [Full Text] [PDF]