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Preconditioning with PKC and the ATP-sensitive potassium channels: a codependent relationship
G R Gaudette1, I B Krukenkamp, A E Saltman
1Division of Cardiothoracic Surgery, University Hospital at Stony Brook and the State University of New York, USA.
The Annals of Thoracic Surgery
|September 2, 2000
Summary
This study reveals that both protein kinase C and potassium channels are essential and interdependent for the heart
Area of Science:
- Cardiovascular Physiology
- Myocardial Preconditioning
- Pharmacology
Background:
- Potassium channel openers and protein kinase C independently induce myoprotective preconditioning.
- The in vivo relationship between these two pathways remains unclear.
Purpose of the Study:
- To investigate the in vivo dependency between potassium channels and protein kinase C in myocardial preconditioning.
- To determine if these pathways are codependent for the protective effect.
Main Methods:
- Thirty-seven sheep were assigned to groups receiving pinacidil (potassium channel opener), 4beta-phorbol-12,13-dibutyrate (PDBu, protein kinase C activator), specific blockers, or combinations.
- Animals underwent 60 minutes of regional ischemia followed by 180 minutes of reperfusion.
- Infarct size and regional function were assessed.
Main Results:
- Both pinacidil and PDBu significantly reduced infarct size compared to controls.
- Blockade of either pathway abolished the preconditioning effect.
- Regional function showed no significant differences across groups.
Conclusions:
- Protein kinase C and potassium channels are necessary for in vivo myocardial preconditioning.
- These two pathways are codependent for eliciting the myoprotective response.