While
therapeutic hypothermia improves the outcomes of individuals in
cardiac arrest, the hemodynamic responses and mechanisms which underlie
hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which
induced hypothermia preserves cardiac function and protects against mitochondrial damage following
cardiac arrest.
Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following
resuscitation, the animals were randomly assigned to a
hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after
resuscitation was significantly better in rats treated with
hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the
hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after
cardiac arrest and
resuscitation, the degree of injury was ameliorated by
hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at
tyrosine 705 and its expression in mitochondria were significantly higher under
hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of
hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated
ischemia and reperfusion.
Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity.