Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis

Hiroyuki Muranaka, Akira Marui*, Masaki Tsukashita, Jian Wang, Jota Nakano, Tadashi Ikeda, Ryuzo Sakata

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: Left ventricular assist devices are used in patients with end-stage dilated cardiomyopathy as a "bridge to recovery." However, physiologic and histologic changes under prolonged mechanical unloading have not been elucidated. Thus, we investigated these changes in the rat heart with dilated cardiomyopathy under mechanical unloading after heterotopic transplantation. Methods: Six weeks after induction of autoimmunized dilated cardiomyopathy in Lewis rats, 2 types of hearts were compared (n = 6 each): (1) an unloaded dilated cardiomyopathy heart (DCM-UL) and (2) a dilated cardiomyopathy heart (DCM). The hearts were evaluated 2 and 4 weeks after transplantation. Results: Four weeks after transplantation, developed tension of the papillary muscle (indicator of myocardial contractility) and β-adrenergic response to isoproterenol were better in DCM-UL than in DCM (P = 0.0025 and P <0.0001, respectively). However, half-relaxation time of the papillary muscle (indicator of myocardial relaxation) was worse in the DCM-UL group (P < .0001). The ratio of the fibrotic area of the myocardium and the number of terminal dUTP nick end-labeling-positive myocytes (indicator of myocardial apoptosis) were higher in DCM-UL than in DCM (P = .0072 and P = .0039, respectively). The mRNA expression of collagen Ia was also higher in DCM-UL. Conclusions: Mechanical unloading preserved myocardial contractility and β-adrenergic response but worsened myocardial relaxation. Furthermore, prolonged mechanical unloading has a tendency to increase the ratio of the fibrotic area and myocardial apoptosis. These unfavorable responses, although secondary to prolonged mechanical unloading, may have a negative impact on the bridge to recovery in patients with dilated cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)916-922
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume140
Issue number4
DOIs
StatePublished - Oct 1 2010

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Dilated Cardiomyopathy
Apoptosis
Papillary Muscles
Adrenergic Agents
Transplantation
Heterotopic Transplantation
Heart-Assist Devices
Isoproterenol
Muscle Cells
Myocardium
Collagen

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

@article{85385e01693f4c12812efbee97e105a0,
title = "Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis",
abstract = "Objective: Left ventricular assist devices are used in patients with end-stage dilated cardiomyopathy as a {"}bridge to recovery.{"} However, physiologic and histologic changes under prolonged mechanical unloading have not been elucidated. Thus, we investigated these changes in the rat heart with dilated cardiomyopathy under mechanical unloading after heterotopic transplantation. Methods: Six weeks after induction of autoimmunized dilated cardiomyopathy in Lewis rats, 2 types of hearts were compared (n = 6 each): (1) an unloaded dilated cardiomyopathy heart (DCM-UL) and (2) a dilated cardiomyopathy heart (DCM). The hearts were evaluated 2 and 4 weeks after transplantation. Results: Four weeks after transplantation, developed tension of the papillary muscle (indicator of myocardial contractility) and β-adrenergic response to isoproterenol were better in DCM-UL than in DCM (P = 0.0025 and P <0.0001, respectively). However, half-relaxation time of the papillary muscle (indicator of myocardial relaxation) was worse in the DCM-UL group (P < .0001). The ratio of the fibrotic area of the myocardium and the number of terminal dUTP nick end-labeling-positive myocytes (indicator of myocardial apoptosis) were higher in DCM-UL than in DCM (P = .0072 and P = .0039, respectively). The mRNA expression of collagen Ia was also higher in DCM-UL. Conclusions: Mechanical unloading preserved myocardial contractility and β-adrenergic response but worsened myocardial relaxation. Furthermore, prolonged mechanical unloading has a tendency to increase the ratio of the fibrotic area and myocardial apoptosis. These unfavorable responses, although secondary to prolonged mechanical unloading, may have a negative impact on the bridge to recovery in patients with dilated cardiomyopathy.",
author = "Hiroyuki Muranaka and Akira Marui and Masaki Tsukashita and Jian Wang and Jota Nakano and Tadashi Ikeda and Ryuzo Sakata",
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Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis. / Muranaka, Hiroyuki; Marui, Akira; Tsukashita, Masaki; Wang, Jian; Nakano, Jota; Ikeda, Tadashi; Sakata, Ryuzo.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 140, No. 4, 01.10.2010, p. 916-922.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis

AU - Muranaka, Hiroyuki

AU - Marui, Akira

AU - Tsukashita, Masaki

AU - Wang, Jian

AU - Nakano, Jota

AU - Ikeda, Tadashi

AU - Sakata, Ryuzo

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Objective: Left ventricular assist devices are used in patients with end-stage dilated cardiomyopathy as a "bridge to recovery." However, physiologic and histologic changes under prolonged mechanical unloading have not been elucidated. Thus, we investigated these changes in the rat heart with dilated cardiomyopathy under mechanical unloading after heterotopic transplantation. Methods: Six weeks after induction of autoimmunized dilated cardiomyopathy in Lewis rats, 2 types of hearts were compared (n = 6 each): (1) an unloaded dilated cardiomyopathy heart (DCM-UL) and (2) a dilated cardiomyopathy heart (DCM). The hearts were evaluated 2 and 4 weeks after transplantation. Results: Four weeks after transplantation, developed tension of the papillary muscle (indicator of myocardial contractility) and β-adrenergic response to isoproterenol were better in DCM-UL than in DCM (P = 0.0025 and P <0.0001, respectively). However, half-relaxation time of the papillary muscle (indicator of myocardial relaxation) was worse in the DCM-UL group (P < .0001). The ratio of the fibrotic area of the myocardium and the number of terminal dUTP nick end-labeling-positive myocytes (indicator of myocardial apoptosis) were higher in DCM-UL than in DCM (P = .0072 and P = .0039, respectively). The mRNA expression of collagen Ia was also higher in DCM-UL. Conclusions: Mechanical unloading preserved myocardial contractility and β-adrenergic response but worsened myocardial relaxation. Furthermore, prolonged mechanical unloading has a tendency to increase the ratio of the fibrotic area and myocardial apoptosis. These unfavorable responses, although secondary to prolonged mechanical unloading, may have a negative impact on the bridge to recovery in patients with dilated cardiomyopathy.

AB - Objective: Left ventricular assist devices are used in patients with end-stage dilated cardiomyopathy as a "bridge to recovery." However, physiologic and histologic changes under prolonged mechanical unloading have not been elucidated. Thus, we investigated these changes in the rat heart with dilated cardiomyopathy under mechanical unloading after heterotopic transplantation. Methods: Six weeks after induction of autoimmunized dilated cardiomyopathy in Lewis rats, 2 types of hearts were compared (n = 6 each): (1) an unloaded dilated cardiomyopathy heart (DCM-UL) and (2) a dilated cardiomyopathy heart (DCM). The hearts were evaluated 2 and 4 weeks after transplantation. Results: Four weeks after transplantation, developed tension of the papillary muscle (indicator of myocardial contractility) and β-adrenergic response to isoproterenol were better in DCM-UL than in DCM (P = 0.0025 and P <0.0001, respectively). However, half-relaxation time of the papillary muscle (indicator of myocardial relaxation) was worse in the DCM-UL group (P < .0001). The ratio of the fibrotic area of the myocardium and the number of terminal dUTP nick end-labeling-positive myocytes (indicator of myocardial apoptosis) were higher in DCM-UL than in DCM (P = .0072 and P = .0039, respectively). The mRNA expression of collagen Ia was also higher in DCM-UL. Conclusions: Mechanical unloading preserved myocardial contractility and β-adrenergic response but worsened myocardial relaxation. Furthermore, prolonged mechanical unloading has a tendency to increase the ratio of the fibrotic area and myocardial apoptosis. These unfavorable responses, although secondary to prolonged mechanical unloading, may have a negative impact on the bridge to recovery in patients with dilated cardiomyopathy.

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U2 - 10.1016/j.jtcvs.2010.02.006

DO - 10.1016/j.jtcvs.2010.02.006

M3 - Article

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VL - 140

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SN - 0022-5223

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