A novel short course, low intensity blood-flow restricted exercise (BFRE) regimen to study satellite cell function in critical illness survivors with sustained muscle atrophy following Intensive Care Unit Acquired Weakness (ICUAW)

Sunita Mathur¹Natalia Maia Parente²Manoela De Paula Ferreira²Christian Martin²Christina Doherty³Judy Correa³Caterina Di Ciano-Oliveira³Pamela J Plant³Jane Batt^3,4*

• ¹School of Rehabilitation Therapy, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada
• ²Department of Physical Therapy, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
• ³Keenan Research Center for Biomedical Science, St Michael’s Hospital Unity Health Toronto, Toronto, Canada
• ⁴Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Introduction: ICU Acquired Weakness (ICUAW) develops in critically ill patients and can persist after hospital discharge, resulting in physical disability. Decreased satellite cell content is reported in the atrophic muscle of critical illness survivors, suggesting that the sustained muscle wasting results from satellite cell dysfunction and impaired muscle regeneration. Intense resistance exercise stimulates satellite cell proliferation and can be used to study the satellite cell role in persisting muscle atrophy following ICU discharge, but the intensity of exercise required can be in-tolerable for older or frail ICU survivors. This study tested the capacity of a novel low intensity, short duration blood flow restricted exercise (BFRE) regimen, de-signed to accommodate the physical exercise limitations of critical illness survivors, to stimulate the satellite cell. . Methods: Eight healthy controls (5 males, 3 females ; ages 20 - 64 years) underwent five consecutive daily sessions of quadriceps BFRE consisting of eight sets of eight knee extensions at 30% isometric peak torque followed by imaging and vastus lat-eralis (VL) biopsy to determine quadriceps size, strength, VL satellite cell content, and transcript expression levels of regulators of muscle proteolysis, autophagy and myogenic regulatory factors pre- and post-BFRE training. The BFRE regimen was piloted in 3 ICUAW survivors (54 - 62 years) five years post-ICU discharge, Results: All study participants tolerated and completed the BFRE regimen. In con-trols, satellite cell content and MuRF1 transcript expression were higher (1.53+/-0.30 and 1.34+/-0.31 fold difference respectively) and myostatin transcript expression lower (0.58+/-0.31 fold difference) in BFRE-trained vs. untrained VL. Two survivors with low quadriceps mass compared to sex- and age- matched population-based norms and study controls, showed no difference in satellite cell content in trained vs. untrained VL. In the survivor with quadriceps mass comparable to population norms and controls, satellite cell content was higher in the BFRE trained vs. un-trained VL. Conclusions: This study demonstrates training with a novel short duration, low intensity BFRE regimen results in a higher satellite cell content in healthy muscle and can be completed by ICUAW survivors. Pilot data suggest that sustained satel-lite cell dysfunction may impede muscle mass reconstitution after ICU discharge.