Moderate hypothermia ameliorates enterocyte mitochondrial dysfunction in severe shock and reperfusion.

BACKGROUND

Hypothermia can ameliorate ischemia-reperfusion-induced intestinal injury; however, whether the therapeutic mechanism of hypothermia on hemorrhagic shock, a severe condition of ischemia-reperfusion, is associated with mitochondrial protection in enterocytes is rarely reported. We aimed to evaluate the effects of hypothermia on mitochondria after shock-induced intestinal injury.

MATERIALS AND METHODS

A severe hemorrhagic shock model was constructed in Sprague-Dawley rats at induced hypothermic (32°C or 34°C) or normothermic temperatures (37°C), followed by resuscitation with whole shed blood and Ringer lactate (15 mg/kg body weight). After 2 h, 24 rats were killed and their intestinal tissue was collected; the remaining animals were returned to the normothermic environment to observe the survival time.

RESULTS

There was severe mitochondrial dysfunction in the normothermia group, as well as increased oxidative stress and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling apoptotic index. As expected, hypothermia treatment decreased mitochondrial permeability transition pore opening and restored the mitochondrial membrane potential and intracellular adenosine triphosphate content. Furthermore, hypothermia elevated mitochondrial-reduced glutathione and decreased mitochondrial malondialdehyde; consistent with the restored mitochondrial function, intestinal cell apoptosis and intestinal histopathologic injury were attenuated, the systemic inflammatory response was mitigated, and survival time was significantly prolonged. Additionally, moderate-induced hypothermia (32°C) had better therapeutic effects than mild hypothermia (34°C).

CONCLUSIONS

The results suggest that moderate hypothermia resuscitation is an effective treatment for shock-induced intestinal injury, and its therapeutic mechanism may be related to mitochondrial protection.