Back to Search
Start Over
Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection
- Source :
- Cardiovascular research. 47(1)
- Publication Year :
- 2000
-
Abstract
- Background: Recent studies have postulated that mitochondrial ATP-sensitive potassium (mitoKATP) channel activation may modulate mitochondrial function with the resultant induction of a preconditioning phenotype in the heart. We hypothesized that the modulation of mitochondrial homeostasis might confer preconditioning-like cardioprotection. Methods: We used a model of regional ischemia in Langendorff-perfused isolated rat hearts. Short-term administration of 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation and cyclosporin A (CSA), an inhibitor of mitochondrial respiration, was used in an attempt to elicit preconditioning-like cardioprotection. The anti-ischemic drug trimetazidine, known to attenuate CSA-induced disruption in mitochondrial function, and the mitoKATP channel blocker 5-hydroxydecanoic acid (5-HD) were used to inhibit the effects of DNP and CSA. Finally, we studied the effect of trimetazidine on adenosine-induced and ischemic preconditioning. Risk zone and infarct size were measured and expressed as a percentage of the risk zone (I/R ratio). Results: DNP, CSA and adenosine pretreatment reduced infarct size (I/R ratio: DNP 9.0±2.4%, CSA 12.5±1.4%, adenosine 11.9±3.6%, all P
- Subjects :
- Male
Physiology
Trimetazidine
Ischemia
Myocardial Ischemia
Pharmacology
Mitochondrion
Mitochondria, Heart
Physiology (medical)
Cyclosporin a
medicine
Animals
Homeostasis
Rats, Long-Evans
Enzyme Inhibitors
Cardioprotection
business.industry
Uncoupling Agents
medicine.disease
Adenosine
Rats
Perfusion
Anesthesia
Ischemic Preconditioning, Myocardial
Cyclosporine
Ischemic preconditioning
Cardiology and Cardiovascular Medicine
business
Hydroxy Acids
Anti-Arrhythmia Agents
Decanoic Acids
Ion channel blocker
Dinitrophenols
medicine.drug
Subjects
Details
- ISSN :
- 00086363
- Volume :
- 47
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cardiovascular research
- Accession number :
- edsair.doi.dedup.....b61c6c610b2d0ab0c08ea1af6a8a75f3