Cour 2011 Eur Heart J

Cour M, Loufouat J, Paillard M, Augeul L, Goudable J, Ovize M, Argaud L (2011) Inhibition of mitochondrial permeability transition to prevent the post-cardiac arrest syndrome: a pre-clinical study. Eur Heart J 32:226-35.

» PMID: 20430770

Cour M, Loufouat J, Paillard M, Augeul L, Goudable J, Ovize M, Argaud L (2011) Eur Heart J

Abstract: Resuscitated cardiac arrest (CA), leading to harmful cardiovascular dysfunction and multiple organ failure, includes a whole-body hypoxia-reoxygenation phenomenon. Opening of the mitochondrial permeability transition pore (mPTP) appears to be a pivotal event in ischaemia-reperfusion injury. We hypothesized that pharmacological inhibition of mPTP opening may prevent the post-CA syndrome.

Anaesthetized New Zealand White rabbits underwent a 15 min primary asphyxial CA and 120 min of reperfusion following resuscitation. At reflow, animals received an intravenous bolus of either cyclosporine A (CsA, 5 mg/kg) or NIM 811 (2.5 mg/kg), two potent inhibitors of mPTP opening, or the CsA vehicle (control). Short-term survival, haemodynamics, regional (sonomicrometry), and global cardiac function (dP/dt and aortic flow) were assessed. We measured markers of cellular injuries and/or organ failure, including troponin Ic release, lacticodehydrogenase, lactate, creatinine, and alanine aminotransferase. Cyclosporine A and NIM 811 significantly improved short-term survival, post-resuscitation cardiac function, as well as liver and kidney failure (P < 0.05). CsA and NIM 811 both attenuated in vitro mPTP opening (calcium retention capacity by spectrofluorimetry) and restored oxidative phosphorylation when compared with controls (P < 0.05).

These data suggest that pharmacological inhibition of mPTP opening, added to basic life support, attenuates the post-CA syndrome and improves short-term outcomes in the rabbit model. • Keywords: Cyclosporine A, Cardiac arrest, Cardiopulmonary resuscitation, Ischaemia, Reperfusion, Pharmacological post-conditioning

• O2k-Network Lab: FR Lyon Ovize M

Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology 

Stress:Ischemia-reperfusion, Permeability transition  Organism: Rabbit  Tissue;cell: Heart  Preparation: Isolated mitochondria 

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

An Oroboros O2k was used in this publication, whereas the Anton Paar/Oroboros Oxygraph was the first-generation instrument for high-resolution respirometry, which was replaced by the O2k in 2002.

• Further details: Gnaiger 2012 Abstract Bioblast-Gentle Science