Exploration of the optimal dose of HOE-642 for the protection of neuronal mitochondrial function after cardiac arrest in rats
| Autor: | Xintong Liu, Fei Han, Lanying Wei, Pengjiao Zhang, Yanan Hu, Xifan Wang, Wenshuai Zhao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Resuscitation Cardiotonic Agents education Diastole Improved survival RM1-950 Mitochondrion Guanidines 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine Animals Sulfones Rats Wistar HOE-642 Pharmacology Asphyxia chemistry.chemical_classification Neurons Reactive oxygen species Dose-Response Relationship Drug business.industry Ischemia-reperfusion General Medicine Ischemic Contracture Hypothermia Cardiac arrest humanities Heart Arrest Rats Mitochondria 030104 developmental biology Endocrinology chemistry 030220 oncology & carcinogenesis CPR Therapeutics. Pharmacology medicine.symptom business Reactive Oxygen Species Anti-Arrhythmia Agents |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 110, Iss, Pp 818-824 (2019) |
| ISSN: | 0753-3322 |
| Popis: | Introduction It has been demonstrated HOE-642 ameliorates ischemic contracture, prevents post-resuscitation diastolic dysfunction, and favors the earlier return of contractile function. This study is the first report to explore the optimal dose of HOE-642 in protecting the neuronal mitochondrial function after cardiac arrest. Methods Cardiac arrest was induced by 8 min asphyxia in rats. There were Sham (S), Normothermic (NORM), and Hypothermic (HYPO) groups. The NORM or HYPO groups consist of four subgroups: NORM/HYPO + HOE-642 0, 1, 3, and 5 mg/kg. Survival and NDS were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, and mitochondrial complex I IV activity of the hippocampus were detected. Results Survival in the HYPO + 1 mg group was the best and significantly higher than in the NORM + 0 mg and NORM + 1 mg groups. NDS in the HYPO + 0 mg, HYPO + 1 mg, and HYPO + 3 mg groups was significantly lower than in the NORM + 0 mg group. ΔΨm in the NORM + 1 mg (n = 5) group was significantly higher than in the NORM + 0 mg (n = 8), NORM + 3 mg (n = 5), and NORM + 5 mg (n = 5) groups. The ROS production in the NORM + 1 mg and NORM + 3 mg groups were significantly lower than in the NORM + 0 mg and NORM + 5 mg groups. Complex I and III activities in the HYPO + 1 mg (n = 5) group were significantly higher than in the HYPO + 3 mg (n = 5), and HYPO + 5 mg (n = 5) groups. Complex II and IV activities in the NORM + 3 mg and HYPO + 3 mg groups were significantly higher than in the NORM + 0 mg, NORM + 1 mg, and HYPO + 0 mg (n = 4)groups. Conclusions HOE-642 1 or 3 mg/kg showed benefits compared to HOE-642 5 mg/kg used when initiating resuscitation. When combined with hypothermia after cardiac arrest, HOE-642 1 or 3 mg/kg improved survival and neurological function compared with hypothermia or HOE-642 alone, however, HOE-642 5 mg/kg plus hypothermia did not. |
| Databáze: | OpenAIRE |
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