Document Detail

Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post-ischaemic functional recovery in rats in vivo.
MedLine Citation:
PMID:  17031386     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: The mitochondrial permeability transition pore (mPTP), an energy-dissipating channel activated by calcium, contributes to reperfusion damage by depolarizing the mitochondrial inner membrane potential. As mitochondrial Ca(2+) overload is a main inductor of mPTP opening, we examined the effect of Ru(360), a selective inhibitor of the mitochondrial calcium uptake system against myocardial damage induced by reperfusion in a rat model.
EXPERIMENTAL APPROACH: Myocardial reperfusion injury was induced by a 5-min occlusion of the left anterior descending coronary artery, followed by a 5-min reperfusion in anaesthetized open-chest rats. We measured reperfusion-induced arrhythmias and functions indicative of unimpaired mitochondrial integrity to evaluate the effect of Ru(360) treatment.
KEY RESULTS: Reperfusion elicited a high incidence of arrhythmias, haemodynamic dysfunction and loss of mitochondrial integrity. A bolus intravenous injection of Ru(360) (15-50 nmol kg(-1)), given 30-min before ischaemia, significantly improved the above mentioned variables in the ischaemic/reperfused myocardium. Calcium uptake in isolated mitochondria from Ru(360)-treated ventricles was partially diminished, suggesting an interaction of this compound with the calcium uniporter.
CONCLUSIONS AND IMPLICATIONS: We showed that Ru(360) treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru(360) administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mPTP. We conclude that myocardial damage could be a consequence of failure of the mitochondrial network to maintain the membrane potential at reperfusion. Hence, it is plausible that Ru(360) could be used in reperfusion therapy to prevent the occurrence of arrhythmia.
G de J García-Rivas; K Carvajal; F Correa; C Zazueta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-09
Journal Detail:
Title:  British journal of pharmacology     Volume:  149     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-27     Completed Date:  2007-02-02     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  829-37     Citation Subset:  IM    
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México DF, México.
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MeSH Terms
Aconitate Hydratase / metabolism
Blood Pressure / drug effects
Calcium / metabolism*
Calcium Channel Blockers / metabolism,  pharmacology*,  therapeutic use
Calcium Channels / drug effects*,  metabolism
Cell Respiration / drug effects
Coronary Circulation / drug effects
Cyclosporine / pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Heart Rate / drug effects
Mitochondria, Heart / drug effects*,  metabolism
Mitochondrial Membrane Transport Proteins / drug effects,  metabolism
Myocardial Reperfusion / adverse effects*
Myocardial Reperfusion Injury / drug therapy*,  metabolism,  physiopathology
Myocytes, Cardiac / drug effects,  metabolism
Rats, Wistar
Ruthenium Compounds / metabolism,  pharmacology*,  therapeutic use
Ruthenium Red / pharmacology
Time Factors
Ventricular Fibrillation / metabolism,  prevention & control
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels; 0/Mitochondrial Membrane Transport Proteins; 0/Ru 360; 0/Ruthenium Compounds; 0/mitochondrial calcium uniporter; 0/mitochondrial permeability transition pore; 11103-72-3/Ruthenium Red; 59865-13-3/Cyclosporine; 7440-70-2/Calcium; EC Hydratase
Comment In:
Br J Pharmacol. 2006 Dec;149(7):811-3   [PMID:  17031384 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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