Small extracellular vesicles (sEVs) are increasingly recognized as crucial mediators of cell-cell communication. This study aims to determine the influence of sEV mediation on cardiomyocytes (CMs) under hypoxic conditions and identify the molecular modifications induced by hypoxia-derived sEVs (H-sEVs). Using a preconditional approach, we administered hypoxic AC16 CM-derived sEVs to recipient AC16 CMs before hypoxic stimulation. Molecular and biochemical analyses were performed to evaluate the biological effects of H-sEVs, e.g., cell viability assay, caspase assays, Western blotting, and quantitative sandwich ELISA. Our results showed a significant decrease in CM viability following hypoxic stimulation, as well as elevated caspase-3 and caspase-8 activity, and increased Bcl-2-associated X protein (BAX) translocation to the mitochondria followed by an increased release of Cytochrome C from mitochondria to cytosol. Preconditioning with H-sEVs further exacerbated caspase-3 and caspase-8 activation, which was explained by aggravated translocation of BAX to the mitochondria with consequences of cytochrome C release and increased apoptotic signaling. Our research indicates that sEVs secreted by hypoxic AC16 CMs negatively impact the biological properties of recipient CMs exposed to hypoxic stress. Thus, these findings widen our current understanding of sEV-mediated cellular communication during hypoxic events and provide insights into potential therapeutic targets for cardiac ischemic injury.

The military population relies on being mentally and physically healthy to perform well during operations. Recent studies indicate that multiple stressors during combat training influence both acute and chronic stress responses in soldiers, ultimately affecting their performance and health. This study investigated the physiological effects of strenuous physical activity, mental strain, sleep deprivation, and energy deficits during four days of simulated combat training (SCT) by analyzing changes in body composition and blood biomarkers, focusing on metabolic changes. This cohort study with a pre- and post-design included 48 cadets (12 females and 36 males) from the Royal Norwegian Air Force Academy, aged 20–29 years, who participated in mandatory SCT. Body composition was measured using bioelectrical impedance (InBody 770), and blood biomarkers were collected through blood samples and capillary blood gas. We observed a significant decrease in total body weight following SCT, including reductions in total body water, muscle mass, and fat mass. Metabolic markers such as pH, pCO2, and base excess were significantly decreased, while the anion gap significantly increased. Lactate levels showed no significant change following SCT. All electrolyte and nutritional markers (triglyceride, glucose, sodium, calcium, and chloride) significantly decreased, except for potassium, which showed no change. These findings support the necessity for comprehensive monitoring and management of metabolic acidosis, electrolyte imbalances, and hydration status in soldiers undergoing SCT. Ensuring sufficient nutrition, hydration, and recovery time is crucial to reduce negative health effects and maintain optimal performance during and following SCT.