Evaluating skeletal muscle dysfunction and recovery in a zymosan model of critical illness in mice

Muscle wasting and weakness are common complications associated with critical illness and admission to the intensive care unit (ICU), which contribute to increased mortality and health deficits post discharge. The mechanisms underlying ICU-acquired muscle weakness (ICU-AW) are incompletely understood, and small-animal models can help address this shortfall and provide experimental platforms for devising therapeutic strategies. We used zymosan treatment to induce wasting and weakness in C57BL/6J mice and evaluated recovery of hindlimb muscles and diaphragm on day (D)4, D7, D14 and D28 after induction of critical illness, through extensive physiological and immunohistological analyses. Tibialis anterior muscles from zymosan-treated mice exhibited atrophy and functional impairment at D4 and D7, with recovery at D14. In contrast, the diaphragm exhibited a delay in wasting and recovery from critical illness, with muscle fibre atrophy at D28, despite inflammatory cell infiltration from D4 and transient impairments in respiratory function. The zymosan mouse model provides important insights into mechanisms underlying the recovery from wasting and weakness after critical illness to better understand and treat ICU-AW.