The effects of chronic alcohol ingestion in mice on contractile properties of cardiac and skeletal muscle: A comparison with normal and dehydrated-malnourished controls

Berk, Steven L.; Block, Paul; Toselli, Paul; Ullrick, William C.

doi:10.1007/bf01945792

Cited by 10 publications

(7 citation statements)

References 6 publications

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“…In addition to specific force measures being similar in EtOH and control mice, we also did not observe a reduction in the twitch‐to‐tetanic torque. These results are similar to reports that observed ex vivo or in situ specific force did not change after mice consumed high concentrations of EtOH for at least 14 weeks (Berk et al, 1975 ; Crowell et al, 2019 ). Furthermore, Crowell et al (2019) demonstrated the ex vivo twitch‐tetanic force ratio assessed in extensor digitorum longus muscle was similar, regardless of treatment (chronic EtOH intake vs. no EtOH) (Crowell et al, 2019 ).…”

Section: Discussionsupporting

confidence: 91%

“…Preclinical studies have largely focused on the molecular alterations associated with muscle atrophy rather than functional outcomes and pathophysiological mechanisms (Kimball & Lang, 2018 ; Lang et al, 2001 ; Simon et al, 2017 ; Slavin et al, 1983 ; Steiner & Lang, 2015 ). In fact, we are aware of only four preclinical studies over the past half century that measured the effects of excessive, long‐duration EtOH consumption on the muscle's force producing capacity (Berk et al, 1975 ; Crowell et al, 2019 ; Edmonds et al, 1987 ; Martyn & Munsat, 1980 ). Functional changes in these studies ranged from no change in the force generating capacity to ~20% deficits in force production during twitch or tetanic isometric contractions using ex vivo (also referred to as in vitro) or in situ physiology.…”

Section: Introductionmentioning

confidence: 99%

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Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy

Moser

Brown

Clark

et al. 2022

Alcoholism Clin & Exp Res

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Background Weakness is a common clinical symptom reported in individuals with chronic alcohol use disorder. However, it remains unclear whether low strength in these individuals is directly related to excessive ethanol intake, other deleterious factors (lifestyle, environment, genetics, etc.), or a combination of both. Therefore, we examined whether (and how) ethanol reduces the muscle’s force‐producing capacity using a controlled in vivo preclinical mouse model of excessive ethanol intake. Methods To establish whether chronic ethanol consumption causes weakness, C57BL/6 female mice consumed 20% ethanol for 40 weeks (following a 2‐week ethanol ramping period), and various measures of muscular force were quantified. Functional measures included all‐limb grip strength and in vivo contractility of the left ankle dorsiflexors and plantarflexors. Once confirmed that mice consuming ethanol were weaker than age‐matched controls, we sought to determine the potential neuromuscular mechanisms of muscle dysfunction by assessing neuromuscular excitation, muscle quantity, and muscle quality. Results Mice consuming chronic ethanol were 13 to 16% weaker (p ≤ 0.016) than controls (i.e., mice consuming 100% water) with the negative impact of ethanol on voluntary grip strength (ƞ2 = 0.603) being slightly larger than that of electrically stimulated muscle contractility (ƞ2 = 0.482). Relative to controls, lean mass and muscle wet masses were 9 to 16% lower in ethanol‐consuming mice (p ≤ 0.048, ƞ2 ≥ 0.268). No significant changes were observed between groups for indices of neuromuscular excitation at the level of the motor unit, neuromuscular junction, or plasmalemma (p ≥ 0.259, ƞ2 ≤ 0.097), nor was muscle quality altered after 40 weeks of 20% ethanol consumption (p ≥ 0.695, ƞ2 ≤ 0.012). Conclusions Together, these findings establish that chronic ethanol consumption in mice induces a substantial weakness in vivo that we interpret to be primarily due to muscle atrophy (i.e., reduced muscle quantity) and possibly, to a lesser degree, loss of central neural drive.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy

Moser

Brown

Clark

et al. 2022

Alcoholism Clin & Exp Res

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“…For example, ethanol (Berk et al, 1975) and the cytotoxic drug doxorubicin (Delgado et al, 2004) are known cardiotoxins in humans and have been used in mice to induce heart failure syndromes. Elevated levels of the non-protein amino acid homocysteine, suggested to be a risk factor for the development of heart failure in humans (Herrmann et al, 2006), have been induced in mice by heterozygous deletion of cystathionine--synthase (Vacek et al, 2009), again modelling a specific cause of heart failure.…”

Section: Toxin-induced Heart Failurementioning

confidence: 99%

Heart failure and mouse models

Breckenridge¹

2010

Disease Models &Amp; Mechanisms

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Heart failure is a common, complex condition with a poor prognosis and increasing incidence. The syndrome of heart failure comprises changes in electrophysiology, contraction and energy metabolism. This complexity, and the interaction of the clinical syndrome with very frequently concurrent medical conditions such as diabetes, means that animal modelling of heart failure is difficult. The current animal models of heart failure in common use do not address several important clinical problems. There have been major recent advances in the understanding of cardiac biology in the healthy and failing myocardium, but these are, as yet, unmatched by advances in therapeutics. Arguably, the development of new animal models of heart failure, or at least adaptation of existing models, will be necessary to fully translate scientific advances in this area into new drugs. This review outlines the mouse models of heart failure in common usage today, and discusses how adaptations in these models may allow easier translation of animal experimentation into the clinical arena.

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“…Until 2022, only four preclinical studies had examined the impact of excessive, chronic EtOH consumption on neuromuscular function (Berk et al, 1975; Crowell et al, 2019; Edmonds et al, 1987; Martyn & Munsat, 1980). Functional changes in these studies ranged from no change in the force‐generating capacity to ~20% deficits during twitch or tetanic isometric contractions using ex vivo or in situ physiology.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal assessment of strength and body composition in a mouse model of chronic alcohol‐related myopathy

Ganjayi

Brown

Baumann

2023

Alcohol: Clinical and Experimental Research

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BackgroundExcessive, chronic alcohol consumption can result in muscle atrophy and weakness (i.e., alcoholic myopathy) that impairs the quality of life. However, the precise mechanisms responsible for ethanol's detrimental impact on skeletal muscle have not been fully elucidated, in part due because the time course of disease development and progression are not well established. Therefore, we examined muscle strength and body composition longitudinally using an established preclinical mouse model of chronic alcoholic myopathy.MethodsTo establish a time course of chronic alcoholic myopathy, we fed High Drinking in the Dark (HDID) female mice (n = 7) 20% ethanol for ~32 weeks (following a 2‐week ethanol ramping period). We assessed in vivo isometric contractility of the left ankle dorsiflexor and lean mass via NMR every 4 weeks. Outcomes were compared with age‐matched control HDID mice that did not consume ethanol (n = 8).ResultsAt study completion, mice who consumed ethanol were 12% weaker than control mice (p = 0.015). Compared to baseline, consuming ethanol resulted in an acute transient reduction in dorsiflexion torque at Week 4 (p = 0.032) that was followed by a second, more sustained reduction at Week 20 (p < 0.001). Changes in lean mass paralleled those of dorsiflexor torque, with ~40% of the variance in dorsiflexor torque being explained by the variance in lean mass of the ethanol group (p < 0.001). Dorsiflexor torque normalized to lean mass (mN·m/g lean mass) did not differ between the ethanol and control groups from Weeks 4 to 32 (p ≥ 0.498).ConclusionsThese results indicate that reductions in muscle mass and strength due to chronic, excessive ethanol intake are dynamic, not necessarily linear, processes. Moreover, the findings confirm that ethanol‐induced weakness is primarily driven by muscle atrophy (i.e., loss of muscle quantity). Future studies should consider how chronic alcoholic myopathy develops and progresses rather than identifying changes after it has been diagnosed.

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The effects of chronic alcohol ingestion in mice on contractile properties of cardiac and skeletal muscle: A comparison with normal and dehydrated-malnourished controls

Cited by 10 publications

References 6 publications

Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy

Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy

Heart failure and mouse models

Longitudinal assessment of strength and body composition in a mouse model of chronic alcohol‐related myopathy

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