Abstract Rationale Evidence from pre-clinical and clinical studies indicates that early mobility interventions during critical illness may improve patient outcomes, such as muscle wasting or brain injury; however, mechanisms driving these benefits remain insufficiently characterized. Extracellular vesicles (EVs), which are secreted by cells and enable intercellular communication, could be one mechanism of organ crosstalk that could be effectors of ICU mobility interventions. The purpose of this study was to examine patterns of circulating EVs in critically ill patients who received cycle ergometry exercise compared to those who received standard of care physical therapy. Methods We performed analysis on 16 participants (7 in the intervention and 9 in the control groups) from a single center randomized control trial, A Study Promoting Critical Illness Recovery in the Elderly (ASPIRE, NCT02963558) and 20 participants (10 in the intervention and 10 in the control groups) from a multicenter randomized control trial, Nutrition and Exercise in Critical Illness Trial (NEXIS, NCT03021902). Adults with acute respiratory failure requiring mechanical ventilation for 48 hours and who were previously physically active underwent in-bed ergometry; control participants received usual care physical therapy. Blood was collected prior to receiving the intervention and three days after study enrollment. EVs in plasma samples were isolated using ExoQuick. The diameter and concentration of EVs were quantified using nanoparticle tracking analysis. To analyze the percentage of skeletal muscle-associated EV, the EVs were labeled with an Alexa Fluor 647-labeled anti-α-sarcoglycan antibody and analyzed by flow cytometry. Statistical analyses with ANOVA or Wilcoxon rank test were performed using GraphPad Prism and data are presented as median IQR. Results There was no significant difference in mean size or concentration of total EV between day 3 and baseline in either control or intervention groups. The proportion of total EVs expressing α-sarcoglycan in the control group nearly doubled from baseline to day 3, increasing from a median of 0.6% to 1.1% (p = 0.01). When comparing the percent change from baseline to day 3, there was a trend toward a greater increase in α-sarcoglycan-positive EVs in the intervention (106% 12, 285) group versus the control group (27% -1, 100 (p = 0.065)) (Fig. 1). Conclusions These results suggest that the abundance of muscle-associated EV increases during critical illness, with a further increase following an early mobility intervention. Understanding the cargo carried by and function of these EVs could increase our understanding of skeletal muscle wasting, organ crosstalk, and the response to mobility interventions in critical illness. This abstract is funded by: NIH R01 HL143452, NIH R03 AG060076, and Wake Forest Claude D Pepper Older Americans Independence Center (OAIC) Pilot Grant
Krall et al. (Fri,) studied this question.