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

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.