Abstract:
:HOE-642 has been shown to provide significant protection in a variety of models of cerebral and myocardial ischemia/reperfusion injury. In this study, we examined the impact of HOE-642, a selective Na+/H+ exchanger 1 inhibitor, with or without hypothermia on neuronal and neuronal mitochondrial function during resuscitation. Cardiac arrest was induced by 8 min of asphyxia in rats. Five groups were included in this study: sham; normothermia (N); HOE-642 (HOE, 1 mg/kg); hypothermia (Hypo, 33±0.5°C); and HOE-642 plus hypothermia (HOE+Hypo). Survival and neurological deficit scores (NDS) were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, mitochondrial complex I-IV activity, and ultrastructural changes of the hippocampal mitochondria were evaluated. Survival in the HOE+Hypo group (85.7%) was higher than in the N group (42.9%) and HOE group (31.8%), P<0.05. NDS in the Hypo and HOE+Hypo groups were lower than in the N and HOE groups, P<0.05. ΔΨm in the HOE group (2.7±0.9) were higher than in the N (1.3±0.3) and Hypo (1.4±0.4) groups, P<0.05. Mitochondrial swelling in the N group was severe than in the HOE and Hypo groups, P<0.05. The production of ROS in the HOE and HOE+Hypo groups were lower than in the N group, P<0.05. Complex I-IV activity in the HOE+Hypo group was higher than in the other groups. The ultrastructure of mitochondria in the N group was severely damaged. The mitochondria maintained structural integrity in the HOE, Hypo and HOE+Hypo groups. HOE-642 plus hypothermia during resuscitation was beneficial than HOE-642 or hypothermia alone.
journal_name
Am J Transl Resjournal_title
American journal of translational researchauthors
Wei L,Zhang P,Hu Y,Zhao W,Liu X,Wang X,Han Fsubject
Has Abstractpub_date
2020-05-15 00:00:00pages
2181-2191issue
5issn
1943-8141journal_volume
12pub_type
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