Experimental animal models of muscle wasting in intensive care unit patients

Abstract

The muscle wasting and loss of muscle function associated with critical illness and intensive care have significant negative consequences for weaning from the respirator, duration of hospital stay, and quality of life for long periods after hospital discharge. There is, accordingly, a significant demand for focused research aiming at improving our understanding of the mechanisms underlying the impaired neuromuscular function in intensive care unit (ICU) patients. However, the study of generalized muscle weakness in critically ill ICU patients is further complicated by the coexistence of multiple independent factors, such as different primary diseases, large variability in pharmacologic treatment, collection of muscle samples several weeks after admission to the ICU, and exposure to causative agents. This has led to the design of specific animal models mimicking ICU conditions. These models have often been used to study the mechanisms underlying the paralysis and muscle wasting associated with acute quadriplegic myopathy in ICU patients. This short review aims at presenting existing and recently introduced experimental animal models mimicking the conditions in the ICU (i.e., models designed to determine the mechanisms underlying the muscle wasting associated with ICU treatment).

Nonsurgically induced disuse muscle atrophy and neuromuscular dysfunction upregulates alpha7 acetylcholine receptors

“…In pathological states or muscle-related genetic disorders, there is loss of muscle mass and decreased muscle strength (Elizabeth and Peter 2007). Muscle wasting can also occur in the absence of systemic or genetic disease states as in spaceflights, prolonged bed rest, limb unloading or plaster casting (Brunelli and Rovere-Querini 2008; Grosset and Onambele-Pearson 2008; Larsson 2007; Kortebein et al 2008; Ferrando et al 2006; Zhang et al 2007; Ferrando et al 1996; Frick et al 2008; Kong et al 2009). Immobilization changes the structure and function of the peripheral neuromuscular system and alters both protein synthesis and degradation (Robinson et al 1991).…”

Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model

“…All these experimental models induce muscle atrophy, but lack significant components of muscle wasting seen in ICU patients due to deep sedation or NMB, such as long-term mechanical ventilation and mechanical silencing caused by lack of weight bearing, and the internal strain produced by activation of contractile elements. There is accordingly a strong demand of an experimental ICU model mimicking ICU conditions, i.e., key factors essential for the muscle wasting and paralysis in ICU patients who develop AQM [23]. We have previously used a porcine ICU model, in which piglets are mechanically ventilated and exposed to NMB, corticosteroids and/or sepsis for 5 days [24].…”

Factors Underlying the Early Limb Muscle Weakness in Acute Quadriplegic Myopathy Using an Experimental ICU Porcine Model

“…There is therefore a compelling need for an experimental ICU model in which these different factors can be studied separately or in combination. Different experimental animal models have been introduced that have given valuable insights [8], but most of these animal models do not include concurrent ICU conditions such as prolonged mechanical ventilation, sedation, immobilization and sepsis together with common interventions used in modern anesthesiology and intensive care, i.e. systemic CS and NMBA administration [8].…”