Key result
mPTP inhibition improves short-term post-resuscitation survival, cardiac function, and multiorgan injury.
Why the study?
Opening of the mitochondrial permeability transition pore is a pivotal event in ischaemia-reperfusion injury after cardiac arrest, and its inhibition may prevent post-cardiac arrest syndrome.
Does pharmacological inhibition of mPTP opening with cyclosporine A or NIM 811 improve short-term survival and cardiac function in a rabbit model of resuscitated cardiac arrest?
Does pharmacological inhibition of mPTP opening with cyclosporine A or NIM 811 improve short-term survival and cardiac function in a rabbit model of resuscitated cardiac arrest?
p-value: p=<0.05
Pharmacological inhibition of mPTP opening with cyclosporine A or NIM 811 attenuates post-cardiac arrest syndrome and improves short-term outcomes in a preclinical rabbit model.
Should not yet change post-arrest care; hypothesis-generating for mPTP inhibition and requires clinical trials.
AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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.
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Cour et al. (2010) studied Post-cardiac arrest syndrome. Cyclosporine A or NIM 811 vs. Vehicle control was evaluated on Short-term survival, haemodynamics, regional and global cardiac function, and markers of cellular injuries and organ failure (p=<0.05). Pharmacological inhibition of mPTP opening with Cyclosporine A or NIM 811 significantly improved short-term survival, post-resuscitation cardiac function, and liver and kidney failure (P<0.05).
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