Mechanisms of Impaired Skeletal Muscle Growth in Intensive Care Unit Acquired Weakness (ICUAW)

Critical illness necessitating admission to an Intensive Care Unit causes a loss of muscle that in many people, is irreversible. The resulting weakness can compromise a person's ability to return to work and live independently. The changes in muscle cellular and molecular biology that result from an episode of critical illness to cause permanent muscle loss and weakness are not understood. Research studies to date have shown that muscle is aggressively broken down during critical illness. Our research group has found that this muscle degradation stops shortly after discharge from the ICU, and that muscle appears to be unable to grow to regain mass and function, as it would normally in health. We have discovered that there are fewer satellite cells, which are muscle progenitor cells responsible for regenerating injured muscle, in the muscle of critical illness survivors with sustained muscle wasting months after discharge from hospital. In this proposal we aim to determine whether this depletion of satellite cells contributes to muscle wasting seen long term after critical illness, and to understand the molecular mechanisms that underlie this impaired muscle growth. Using local freezing, we are able to easily perform a small biopsy of the muscle of individuals in the ICU, during their illness, and following discharge home. By studying the response of the muscle to stimulus provided to maximize its opportunity to grow and enlarge at a molecular level, we aim to identify the cellular signalling networks and biologic processes that are inhibiting muscle recovery long term.