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Ubiquitous protective effects of cyclosporine A in preventing cardiac arrest-induced multiple organ failure.
MedLine Citation:
PMID:  25213634     Owner:  NLM     Status:  Publisher    
Opening of the mitochondrial permeability transition pore (mPTP) appears to be a pivotal event in myocardial ischemia-reperfusion (I/R) injury. Resuscitated cardiac arrest (CA) leads to the post-CA syndrome that encompasses, not only myocardial dysfunction, but also brain injury, failure of other organs (kidney, liver or lung), and systemic response to I/R. We aimed to determine whether cyclosporine A (CsA) might prevent multiple organ failure following CA through a ubiquitous mPTP inhibition in each distant vital organ. Anesthetized NZW rabbits were subjected to 15 minutes of CA and 120 minutes of reperfusion. At the onset of resuscitation the rabbits received CsA, its non-immunosuppressive derivative NIM811, or vehicle (controls). Survival, hemodynamics, brain damage, organ injuries and systemic I/R response were analyzed. Fresh mitochondria were isolated from the brain, heart, kidney, liver and lung to assess both oxidative phosphorylation and permeability transition. CsA-analogs significantly improved short-term survival and prevented multiple organ failure, including brain damage and myocardial dysfunction (p<0.05 vs controls). Susceptibility of mPTP opening was significantly increased in heart, brain, kidney, and liver mitochondria isolated from controls, while mitochondrial respiration was impaired (p<0.05 vs Sham). CsA-analogs prevented these mitochondrial dysfunctions (p<0.05 vs controls). These results suggest that CsA and NIM811 can prevent the post-CA syndrome through a ubiquitous mitochondrial protective effect at the level of each major distant organ.
Martin Cour; Maryline Abrial; Vincent Jahandiez; Joseph Loufouat; Elise Belaïdi; Abdallah Gharib; Annie Varennes; Guillaume Monneret; Hélène Thibault; Michel Ovize; Laurent Argaud
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-11
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  -     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, Journal of Applied Physiology.
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