Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1.
BACKGROUND
Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats.


METHODS
The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed.


RESULTS
Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (CcO), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 (P<0.05).


CONCLUSIONS
The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression.
Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, China.
Long
L
Yang
Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, China.
Peng
P
Xie
Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, China.
Jianjiang
J
Wu
Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, China.
Jin
J
Yu
Guizhou Key Laboratory of Anesthesia and Organ Protection, Department of Anesthesiology, Zunyi Medical College Zunyi, Guizhou, China.
Tian
T
Yu
Guizhou Key Laboratory of Anesthesia and Organ Protection, Department of Anesthesiology, Zunyi Medical College Zunyi, Guizhou, China.
Haiying
H
Wang
Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, China.
Jiang
J
Wang
Department of Anesthesiology, The University of Hong Kong Pokfulam, Hong Kong, China.
Zhengyuan
Z
Xia
Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, China.
Hong
H
Zheng
Sevoflurane postconditioning; hypoxia-inducible factor-1; mitochondrial respiratory function; myocardial protective effect; respiratory enzyme activity