Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment

Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible

Isokinetic Muscle Strength and Fatigue Evaluation Following a Combined Aerobic and Resistance Training Program on a Gravity Independent Flywheel Device

Exposure to microgravity imposes changes on the musculoskeletal and cardiovascular systems leading to decreases in aerobic capacity, muscular strength, and muscular fatigue (1). Anti-gravity muscles, those that play a postural role in a standard gravity environment such as the soleus and quadriceps, are most affected by microgravity (2) with nearly all musculature affected with extended spaceflight (3). The multi-mode exercise device (M-MED) is a gravity independent device that provides both high force resistance type and low force aerobic type modes of exercise. Consequently, the M-MED has the ability to enhance both skeletal muscle function through resistance training exercises as well as cardiovascular function with aerobic training

Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment.

Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible

Skeletal muscle unweighting: spaceflight and ground-based models

Long-term manned spaceflight requires that flight crews be exposed to extended periods of unweighting of antigravity skeletal muscles. This exposure will result in adaptations in these muscles that have the potential to debilitate crew members on return to increased gravity environments. Therefore, the development of countermeasures to prevent these unwanted adaptations is an important requirement. The limited access to microgravity environments for the purpose of studying muscle adaptation and evaluating countermeasure programs has necessitated the use of ground-based models to conduct both basic and applied muscle physiology research. In this review, the published results from ground-based models of muscle unweighting are presented and compared with the results from related spaceflight research. The models of skeletal muscle unweighting with a sufficient body of literature included bed rest, cast immobilization, and unilateral lower limb suspension. Comparisons of changes in muscle strength and size between these models in the context of the limited results available from spaceflight suggest that each model may be useful for the investigation of certain aspects of the skeletal muscle unweighting that occur in microgravity. </jats:p

Maintenance of slow type I myosin protein and mRNA expression in overwintering prairie dogs (\u3ci\u3eCynomys leucurus\u3c/i\u3e and \u3ci\u3eludovicianus\u3c/i\u3e) and black bears (\u3ci\u3eUrsus americanus\u3c/i\u3e)

Hibernating mammals have the remarkable ability to withstand long periods of fasting and reduced activity with dramatic maintenance of skeletal muscle function and protein composition. We investigated several hindlimb muscles of white-tailed prairie dogs (Cynomys leucurus) and black bears (Ursus americanus), two very different hibernators who are dormant and fasting during winter. The black-tailed prairie dog (C. ludovicianus) remains active during winter, but suffers minor skeletal muscle atrophy; nevertheless, they also demonstrate apparent skeletal muscle adaptations. Using SDS-PAGE, we measured myosin protein isoform profiles before and after the hibernation season. All species maintained or increased levels of slow myosin, despite the collective physiological challenges of hypophagia and reduced activity. This contrasts markedly with standard mammalian models of skeletal muscle inactivity and atrophy predicting significant loss of slow myosin. A mechanism for changes in myosin isoforms was investigated using reverse-transcription PCR, following partial sequencing of the adult MHC isoforms in C. leucurus and U. americanus. However, mRNA expression was not well correlated with changes in MHC protein isoforms, and other synthesis and degradation pathways may be involved besides transcriptional control. The muscles of hibernating mammals demonstrate surprising and varied physiological responses to inactivity and atrophy with respect to slow MHC expression

Cellular and molecular responses to increased skeletal muscle loading after irradiation

Irradiation of rat skeletal muscles before increased loading has been shown to prevent compensatory hypertrophy for periods of up to 4 wk, possibly by preventing satellite cells from proliferating and providing new myonuclei. Recent work suggested that stem cell populations exist that might allow irradiated muscles to eventually hypertrophy over time. We report that irradiation essentially prevented hypertrophy in rat muscles subjected to 3 mo of functional overload (OL-Ir). The time course and magnitude of changes in cellular and molecular markers of anabolic and myogenic responses were similar in the OL-Ir and the contralateral nonirradiated, overloaded (OL) muscles for the first 3–7 days. These markers then returned to control levels in OL-Ir muscles while remaining elevated in OL muscles. The number of myonuclei and amount of DNA were increased markedly in OL but not OL-Ir muscles. Thus it appears that stem cells were not added to the irradiated muscles in this time period. These data are consistent with the theory that the addition of new myonuclei may be required for compensatory hypertrophy in the rat.</jats:p