Effects of Mdivi‐1 on Extending the Golden Treatment Time following Hemorrhagic Shock in Hot Environment in Rats

Abstract It is found that a hot environment aggravates hemorrhagic shock‐induced internal environment and organ dysfunction. Meanwhile mitochondria show over‐fission. Whether inhibition of mitochondrial fission benefits from the early treatment of hemorrhagic shock under a hot environment is unclear. An uncontrolled hemorrhagic shock model in rats is used, and the effects of mitochondrial fission inhibitor mdivi‐1 on mitochondrial function, organ function, and survival rate of rats are measured. The results show that 0.1–3 mg/kg mdivi‐1 antagonizes hemorrhagic shock‐induced mitochondrial fragment. In addition, mdivi‐1 improves mitochondrial function, and alleviates hemorrhagic shock‐induced oxidative stress and inflammation under a hot environment. Further studies show that 0.1–3 mg/kg Mdivi‐1 reduces blood loss, and maintains a mean artery pressure (MAP) of 50–60 mmHg before bleeding‐stops after hemorrhagic shock, compared with single Lactate Ringer's (LR) resuscitation. Notably, 1 mg/kg of Mdivi‐1 extends the time of hypotensive resuscitation to 2–3 h. During 1 or 2 h of ligation, Mdivi‐1 prolongs survival time and protects vital organ function by rescuing mitochondrial morphology and improving mitochondrial function. These results suggest Mdivi‐1 is suitable for the early treatment of hemorrhagic shock under a hot environment and can extend the golden treatment time to 2–3 hour for hemorrhagic shock under a hot environment.