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. |
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. β’ Keywords: Cyclosporine A, Cardiac arrest, Cardiopulmonary resuscitation, Ischaemia, Reperfusion, Pharmacological post-conditioning
β’ 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