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Jahandiez 2017 Basic Res Cardiol

From Bioblast
Publications in the MiPMap
Jahandiez V, Cour M, Bochaton T, Abrial M, Loufouat J, Gharib A, Varennes A, Ovize M, Argaud L (2017) Fast therapeutic hypothermia prevents post-cardiac arrest syndrome through cyclophilin D-mediated mitochondrial permeability transition inhibition. Basic Res Cardiol 112:35.

ยป PMID: 28492973

Jahandiez V, Cour M, Bochaton T, Abrial M, Loufouat J, Gharib A, Varennes A, Ovize M, Argaud L (2017) Basic Res Cardiol

Abstract: The opening of the mitochondrial permeability transition pore (PTP), which is regulated by the matrix protein cyclophilin D (CypD), plays a key role in the pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated PTP inhibition in both heart and brain. In addition, we investigated whether specific pharmacological PTP inhibition would confer additive protection to cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by 120 min of reperfusion. Five groups (n = 10-15/group) were studied: control group (CA only), hypothermia group (HT, hypothermia at 32-34 ยฐC induced by external cooling at reperfusion), NIM group (injection at reperfusion of 2.5 mg/kg NIM811, a specific CypD inhibitor), HT + NIM, and sham group. The following measurements were taken: hemodynamics, echocardiography, and cellular damage markers (including S100ฮฒ protein and troponin Ic). Oxidative phosphorylation and PTP opening were assessed on mitochondria isolated from both brain and heart. Acetylation of CypD was measured by immunoprecipitation in both the cerebral cortex and myocardium. Hypothermia and NIM811 significantly prevented cardiovascular dysfunction, pupillary areflexia, and early tissue damage. Hypothermia and NIM811 preserved oxidative phosphorylation, limited PTP opening in both brain and heart mitochondria and prevented increase in CypD acetylation in brain. There were no additive beneficial effects in the combination of NIM811 and therapeutic hypothermia. In conclusion, therapeutic hypothermia limited post-CA syndrome by preventing mitochondrial permeability transition mainly through a CypD-dependent mechanism. โ€ข Keywords: Cardiac arrest; Cardiopulmonary resuscitation; Mitochondria; Mitochondrial permeability transition pore; Therapeutic hypothermia โ€ข Bioblast editor: Kandolf G โ€ข O2k-Network Lab: FR Lyon Ovize M


Labels: MiParea: Respiration  Pathology: Cardiovascular  Stress:Permeability transition, Temperature  Organism: Rabbit  Tissue;cell: Heart, Nervous system  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 

2017-08