Skeletal Muscle Regeneration in Survivors of Critical Illness: How to Prevent Satellite Cell Failure?
Trial Parameters
Brief Summary
Modern intensive care enables patients to survive insults that in the past would have been supralethal. Nonetheless, increased number of survivors suffer from failed functional outcomes associated with prolonged muscle weakness and fatiguability. Whilst alterations of skeletal muscle biology that occur during critical illness slowly disappear over the period of months, muscle weakness remains. Recent pilot studies have shown that muscle weakness is associated with loss and alteration of satellite skeletal muscle cells, which are supposed to proliferate and repair damaged muscle tissue. The pathogenesis of this phenomenon has not been fully understood. In this grant project, we will study function and structure of satellite cells and their organelles (particularly mitochondria) using both classical bioenergetics and advanced microscopic techniques. Satellite cells will be isolated from biopsies taken from critically ill patients with developed muscle weakness in the acute and protracted phase of a disease and after 6 months. In time points, an ultrasound examination of muscle mass will be performed, and metabolism will be assessed using insulin clamps. In an in vitro experiments, we will test also effect of nutritional and anabolic factors and drugs, commonly used in ICU, on satellite cells. In a control branch, cells will be isolated from skeletal muscle of volunteers undergoing elective hip replacement surgery. Results of this study could significantly contribute to understanding of mechanisms leading to ICU acquired muscle weakness and to identify therapeutic strategy in future.
Eligibility Criteria
Eligibility Criteria for group of Critically ill patients: Inclusion Criteria: * Critically ill patients receiving mechanical ventilation, to be enrolled within 72 hours of admission, who are likely to need 7 days or more of ICU stay * Sudden onset of disease, which can be determined in time (such as trauma, stroke, sudden cardiac arrest etc.) * Informed consent signed by patient or patient's representative Exclusion Criteria: * Unlikely to survive 6 months * Premorbid downslope functional trajectory or poor performance status (ECOG Gr. 3 or worse) or baseline functional status unknown * Bleeding disorder (INR≥1.5 or PLT\< that would preclude muscle biopsies) * Known mitochondrial disease * Endocrine crisis as a reason for admission * Pregnant women Eligibility Criteria for a control group: Elective hip surgery patients with a very good to excellent performance status, only limited to joint pain (ECOG 0)