A comparison of therapeutic hypothermia and genetic mitochondrial permeability transition pore inhibition in a murine model of cardiac arrest - 26/03/18
Résumé |
Introduction |
Recent evidence suggests that therapeutic hypothermia limits the severity of the post-cardiac arrest syndrome by inhibiting mitochondrial permeability transition pore (mPTP) opening through a Cyclophilin-D (CypD) dependent mechanism.
Objective |
We sought to compare the effects of genetic loss of CypD (CypD-KO) and therapeutic hypothermia on resuscitability and survival after cardiac arrest (CA).
Method |
Adult mice underwent 5minutes of asphyxial CA followed by resuscitation. Animals were assigned to one of the 5 following groups: Sham, Control (Ctrl): normothermic CA in wild-type mice, CypD-KO: normothermic CA in CypD-KO mice, therapeutic hypothermia (TH): CA in wild-type mice with fast hypothermia induced by external cooling at the onset of cardiac massage (33°C for 1hour) and CypD-KO+TH. Two hours after CA, left ventricle-shortening fraction, blood levels of S100B protein (a marker of brain injury) and troponin Ic, were assessed. Additional mice were included in the same 5 groups for survival follow-up.
Results |
Baseline characteristics and characteristics of CA were similar among groups. Rate of restoration of spontaneous circulation (ROSC) was significantly higher in CypD-KO and TH groups compared to controls (P<0.05). Time to ROSC was significantly shorter in CypD-KO mice versus wild-type mice (P<0.05). Genetic loss of CypD and therapeutic hypothermia prevented to a similar extent CA-induced myocardial dysfunction, increase in S100B, troponin Ic and death within 24hours after CA (P<0.05 versus Ctrl). Only therapeutic hypothermia applied to either wild-type or CypD-KO animals improved survival at day 7 (P<0.05 versus non-hypothermic groups). There were no additive beneficial effects in the combination of genetic loss of CypD and therapeutic hypothermia.
Conclusion |
In our CA model, genetic inhibition of CypD improved resuscitability and early cardiac dysfunction but, unlike therapeutic hypothermia, failed to improve 7-day survival.
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Vol 10 - N° 2
P. 184 - avril 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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