Protective effects of mitochondrial fission inhibitor, Mdivi-1, on traumatic shock rats at high altitude

Abstract

Objective To observe the early therapeutic effects of a mitochondrial fission inhibitor, mitochondrial division inhibitor 1 (Mdivi-1), on the traumatic shock rats at high altitude. Methods SD rats were rapidly transported (airlift) from the plain (Chongqing) to the plateau (Lhasa, 3 600 m altitude). After 72 h, the traumatic shock model of rats at high altitude was prepared by free bleeding from splenic artery disconnection until mean arterial pressure (MAP) fell to 40 mmHg. The animals were divided into 5 groups: sham-operation group, shock group, Lactate Ringer's (LR) solution control group, and LR combined with 0.1 and 0.5 mg/kg Mdivi-1 groups. Then the experiments were designed as 2 parts. The rats in the first part were resuscitated with mere LR solution or combined with 0.1 or 0.5 mg/kg Mdivi-1 without hemostatic treatment. With the MAP maintained at 50-60 mmHg, the changes of MAP, bleeding volume, fluid infusion volume and survival rate were observed in each group. In the second part, bleeding control was performed by ligation of the spleen artery after 1 h of low-pressure resuscitation, and definitive resuscitation was continuously given. The changes of blood loss, infusion volume, organ functions, tissue oxygen partial pressure, lung and brain water content and animal survival were subsequently investigated. Results When LR solution was used for low-pressure resuscitation without hemostatic treatment, the MAP of rats was maintained at 50-60 mmHg for about 1 h, and then began to drop gradually rather than rise after increasing the amount of fluid input, with the bleeding volume soared obviously. Whereas Mdivi-1 combination treatment maintained MAP at 50-60 mmHg for about 3 h, and significantly reduced the bleeding volume and fluid infusion. Further studies showed that in the hemostatic resuscitation treatment, the rats of the LR control group still had a rather low level of tissue oxygen partial pressure, with elevated water contents in the lung and brain, and seriously impaired functions of vital organs such as the heart, liver and kidney. However, Mdivi-1 (0.1 or 0.5 mg/kg) treatment remarkably improved the damage, increased the tissue oxygen partial pressure, reduced the water contents in the lung and brain, alleviated the impairment of the heart, liver and kidney, and greatly prolonged the survival time of shock animals. Conclusion Mdivi-1 is suitable for the early treatment of traumatic shock at high altitude, which can improve organ functions and extend the golden time of treatment.

Keywords

• shock
• high altitude
• mitochondrial fission inhibitor
• mdivi-1