Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model

Masami Sugihara, Fuminori Odagiri, Takeshi Suzuki, Takashi Murayama, Yuji Nakazato, Kana Unuma, Ken Ichi Yoshida, Hiroyuki Daida, Takashi Sakurai, Sachio Morimoto, Nagomi Kurebayashi

Research output: Contribution to journalArticle

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Abstract

Background: Inherited dilated cardiomyopathy (DCM) is a progressive disease that often results in death from congestive heart failure (CHF) or sudden cardiac death (SCD). Mouse models with human DCM mutation are useful to investigate the developmental mechanisms of CHF and SCD, but knowledge of the severity of CHF in live mice is necessary. We aimed to diagnose CHF in live DCM model mice by measuring voluntary exercise using a running wheel and to determine causes of death in these mice. Methodology/Principal Findings: A knock-in mouse with a mutation in cardiac troponin T (ΔK210) (DCM mouse), which results in frequent death with a t1/2 of 70 to 90 days, was used as a DCM model. Until 2 months of age, average wheel-running activity was similar between wild-type and DCM mice (approximately 7 km/day). At approximately 3 months, some DCM mice demonstrated low running activity (LO: <1 km/day) while others maintained high running activity (HI: >5 km/day). In the LO group, the lung weight/body weight ratio was much higher than that in the other groups, and the lungs were infiltrated with hemosiderin-loaded alveolar macrophages. Furthermore, echocardiography showed more severe ventricular dilation and a lower ejection fraction, whereas Electrocardiography (ECG) revealed QRS widening. There were two patterns in the time courses of running activity before death in DCM mice: deaths with maintained activity and deaths with decreased activity. Conclusions/Significance: Our results indicate that DCM mice with low running activity developed severe CHF and that running wheels are useful for detection of CHF in mouse models. We found that approximately half of ΔK210 DCM mice die suddenly before onset of CHF, whereas others develop CHF, deteriorate within 10 to 20 days, and die.

Original languageEnglish
Article numbere55514
JournalPloS one
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 31 2013

Fingerprint

cardiomyopathy
Dilated Cardiomyopathy
heart failure
wheels
Running
Wheels
Heart Failure
animal models
death
mice
Sudden Cardiac Death
Hemosiderin
Echocardiography
Troponin T
lungs
hemosiderin
troponin T
mutation
Electrocardiography
electrocardiography

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Sugihara, M., Odagiri, F., Suzuki, T., Murayama, T., Nakazato, Y., Unuma, K., ... Kurebayashi, N. (2013). Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model. PloS one, 8(1), [e55514]. https://doi.org/10.1371/journal.pone.0055514

Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model. / Sugihara, Masami; Odagiri, Fuminori; Suzuki, Takeshi; Murayama, Takashi; Nakazato, Yuji; Unuma, Kana; Yoshida, Ken Ichi; Daida, Hiroyuki; Sakurai, Takashi; Morimoto, Sachio; Kurebayashi, Nagomi.

In: PloS one, Vol. 8, No. 1, e55514, 31.01.2013.

Research output: Contribution to journalArticle

Sugihara, M, Odagiri, F, Suzuki, T, Murayama, T, Nakazato, Y, Unuma, K, Yoshida, KI, Daida, H, Sakurai, T, Morimoto, S & Kurebayashi, N 2013, 'Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model', PloS one, vol. 8, no. 1, e55514. https://doi.org/10.1371/journal.pone.0055514
Sugihara, Masami ; Odagiri, Fuminori ; Suzuki, Takeshi ; Murayama, Takashi ; Nakazato, Yuji ; Unuma, Kana ; Yoshida, Ken Ichi ; Daida, Hiroyuki ; Sakurai, Takashi ; Morimoto, Sachio ; Kurebayashi, Nagomi. / Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model. In: PloS one. 2013 ; Vol. 8, No. 1.
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AU - Nakazato, Yuji

AU - Unuma, Kana

AU - Yoshida, Ken Ichi

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AB - Background: Inherited dilated cardiomyopathy (DCM) is a progressive disease that often results in death from congestive heart failure (CHF) or sudden cardiac death (SCD). Mouse models with human DCM mutation are useful to investigate the developmental mechanisms of CHF and SCD, but knowledge of the severity of CHF in live mice is necessary. We aimed to diagnose CHF in live DCM model mice by measuring voluntary exercise using a running wheel and to determine causes of death in these mice. Methodology/Principal Findings: A knock-in mouse with a mutation in cardiac troponin T (ΔK210) (DCM mouse), which results in frequent death with a t1/2 of 70 to 90 days, was used as a DCM model. Until 2 months of age, average wheel-running activity was similar between wild-type and DCM mice (approximately 7 km/day). At approximately 3 months, some DCM mice demonstrated low running activity (LO: <1 km/day) while others maintained high running activity (HI: >5 km/day). In the LO group, the lung weight/body weight ratio was much higher than that in the other groups, and the lungs were infiltrated with hemosiderin-loaded alveolar macrophages. Furthermore, echocardiography showed more severe ventricular dilation and a lower ejection fraction, whereas Electrocardiography (ECG) revealed QRS widening. There were two patterns in the time courses of running activity before death in DCM mice: deaths with maintained activity and deaths with decreased activity. Conclusions/Significance: Our results indicate that DCM mice with low running activity developed severe CHF and that running wheels are useful for detection of CHF in mouse models. We found that approximately half of ΔK210 DCM mice die suddenly before onset of CHF, whereas others develop CHF, deteriorate within 10 to 20 days, and die.

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