Abstract 255: Therapeutic Hypothermia Ameliorates Sepsis-Induced Myocardial Mitochondrial Dysfunction

Abstract

Introduction: Mitochondrial dysfunction play an important roles during the sepsis induce organ failure. Therapeutic hypothermia can protect mitochondrial dysfunction during injury. How the therapeutic hypothermia acts on septic myocardial mitochondria is still not well explored. Hypothesis: Therapeutic hypothermia is beneficial sepsis induced myocardial mitochondrial dysfunction and survival. Methods: Sepsis was induced in 10-12 week specific-pathogen-free bred male adult Sprague-Dawley rats by cecal ligation and tube insertion. Rats were randomized into controlled normothermia (36-37.5°C) or therapeutic hypothermia (32-34°C) at sepsis induced 6 hours later. The animal heart was harvested at 1 hour after temperature control and mitochondrial was isolated by differential centrifugation. Results: Therapeutic Hypothermia group (n=18) can significantly improve 72 hours survival than the Normothermia group (n=20, p= 0.0031< 0.05). Mitochondrial membrane potential has trend to deteriorat in sepsis (n=13) compared to Sham.( n=18, p=0.062 >0.05). Temperature management did not maintained the membrane potential (Normothermia n= 7, Hypothermia n=5, sepsis vs. normothermia p= 0.98; sepsis vs. hypothermia p=0.88). Myocardial mitochondria oxidative phosphorylation complexes activity including Complex I+III, Complex II+III and Complex IV were worse in sepsis (n=9) compared to Sham (n=14) group. Temperature control can significantly improved the activity either in therapeutic hypothermia ( n=4) and normothermia groups (n=6) except Complex I+II in therapeutic hypothermia group. (Figure) Conclusion: Therapeutic hypothermia preserves mitochondrial oxidative phosphorylation complexes activity in sepsis myocardium and indeed benefit for sepsis prognosis.