Role of excessive mitochondrial fission in seawater immersion aggravated hemorrhagic shock-induced cardiac injury and the protective effect of Mdivi-1.

Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment are still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders, whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction were observed. Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mito-chondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure, activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure, hemodynamic disorders, and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor Mdivi-1 can signifi-cantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy and apoptosis, and then protecting circulation and vital organ functions, prolonging animal survival. Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction, due to the mitochondrial structure and bioenergetics impairment.