Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors

A brief period of myocardial ischemia can result in an increased resistance to subsequent, more severe episodes of ischemia. Recent studies have indicated that activation of adenosine A1-receptors may mediate this preconditioning effect. It is also known that A1-activation can lead to ATP-sensitive...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1992-10, Vol.86 (4), p.1310-1316
Main Authors: GROVER, G. J, SLEPH, P. G, DZWONCZYK, S
Format: Article
Language:English
Subjects:
Adaptation, Physiological - drug effects
Adenosine Triphosphate - pharmacology
Animals
Biological and medical sciences
Cardiology. Vascular system
Coronary Disease - physiopathology
Coronary heart disease
Dogs
Female
Heart
Heart - drug effects
Heart - physiopathology
Male
Medical sciences
Myocardial Reperfusion
Myocardium - metabolism
Phenylisopropyladenosine - pharmacology
Potassium Channels - drug effects
Potassium Channels - physiology
Purinergic Antagonists
Receptors, Purinergic - physiology
Space life sciences
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Summary:A brief period of myocardial ischemia can result in an increased resistance to subsequent, more severe episodes of ischemia. Recent studies have indicated that activation of adenosine A1-receptors may mediate this preconditioning effect. It is also known that A1-activation can lead to ATP-sensitive potassium channel (KATP) opening via a G(i) protein-mediated effect. Thus, we determined whether the KATP blocker glyburide could abolish preconditioning or the protective effects of A1-receptor activation. Anesthetized dogs were subjected to 5 minutes of left circumflex coronary artery (LCx) occlusion (or sham) followed by 10 minutes of reperfusion. The hearts were then subjected to 60 minutes of LCx occlusion and 5 hours of reperfusion. Glyburide (5 micrograms/kg/min) or vehicle was given directly into the LCx 20 minutes before preconditioning or sham preconditioning. Preconditioning resulted in a significantly reduced infarct size compared with nonpreconditioned animals. Glyburide abolished the protective effect of preconditioning. To establish a link between KATP and A1-receptor activation, the effect of the A1-agonist R-PIA with or without glyburide on infarct size was determined. R-PIA (0.4 microgram/kg/min, directly into the LCx) significantly reduced infarct size, and this protective effect was abolished by glyburide. None of the treatments described above had a significant effect on peripheral hemodynamic status or myocardial blood flow. Preconditioning may be mediated by KATP activation, and this may be linked to A1-receptor stimulation.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.86.4.1310