Beyond acute kidney injury, traumatic rhabdomyolysis associated to hemorrhagic shock is responsible for multiple-organ failure in a rat model

ABSTRACT Introduction In severe trauma patients, rhabdomyolysis (RM) and hemorrhagic shock (HS) usually coexist but combined impact of RM and HS has rarely been analyzed. In this study, we aimed to explore simultaneous exposure to RM and HS to investigate our hypothesis that double insult is responsible for multi-organ failure leading to excess mortality. Methods 88 anesthetized male rats were subjected to glycerol-induced RM (three increasing doses of glycerol from 2 to 8 ml/kg) and/or controlled HS (target hypotension = 35 mmHg). Survival time and blood pressure were monitored. Analyses of serum biomarkers for the heart, brain, liver, and kidneys, along with cytokine measurements and histological examinations of the kidneys, liver, and intestine, were conducted. Results The co-occurrence of RM and HS led to precocious and dose-dependent mortality compared to groups with only one injury. This double insult was accompanied by severe, multi-organ damage marked by histological lesions in the kidneys, liver, and intestine, which were associated with elevated corresponding biological parameters. Moreover, biomarkers for the brain (NSE, protein S100) and heart were increased in cases of dual insult. Lastly, HS and RM association was responsible for intense lactic acidosis and an explosive secretion of pro-inflammatory cytokines. Conclusions We developed a rat model to study the synergistic effects of RM and HS, showing that combined injuries caused RM dose-dependent mortality, multi-organ damage and severe inflammation. Further research is needed to elucidate the underlying pathophysiological mechanisms of this synergy.