Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate

• Published in: Cardiovascular research 1992-11, Vol.26 (11), p.1054-1062
• Main Authors: Auchampach, John A, Grover, Gary J, Gross, Garrett J
• Format: Article
• Language: English
• Subjects: Animals; Benzopyrans - pharmacology; Blood Glucose - metabolism; Blood Pressure - drug effects; Coronary Circulation - drug effects; Coronary Circulation - physiology; Coronary Vessels - physiology; Decanoic Acids - pharmacology; Dihydropyridines - pharmacology; Dogs; glibenclamide; Glyburide - pharmacology; Heart Rate - drug effects; Hydroxy Acids - pharmacology; infarct size; ischaemic preconditioning; KATP channels; myocardial ischaemia; Myocardial Ischemia - metabolism; Myocardium - metabolism; Potassium - antagonists & inhibitors; Potassium Channels - metabolism; sodium 5-hydroxydecanoate; Vasodilator Agents - pharmacology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/26.11.1054

Objective: The aims were (1) to determine if a new ischaemia selective ATP dependent potassium (KATP) channel antagonist, sodium 5-hydroxydecanoate (5-HD), blocks ischaemic preconditioning in dogs; (2) to determine whether a small intracoronary dose of glibenclamide, a classical sulphonylurea KATP channel antagonist, could block ischaemic preconditioning independent of systemic metabolic effects. Methods: Barbitone anaesthetised dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 5 h of reperfusion. Preconditioning was produced by a single 5 min left circumflex occlusion followed by 10 min of reperfusion prior to the 60 min occlusion period. 5-HD (150 μg·kg−1·min−1) or vehicle was given by intracoronary infusion into the ischaemic region over 20 min, beginning 15 min prior to the 60 min occlusion period in the presence or absence of preconditioning. Glibenclamide (3 μg·kg−1·min−1) was given by intracoronary infusion into the left circumflex artery during the 5 min preconditioning period or during the first 5 min of occlusion in preconditioned or non-preconditioned dogs. Transmural myocardial blood flow was measured by radioactive microspheres and infarct size determined by triphenyltetrazolium staining and expressed as a percent of the area at risk. Results: There were no differences in haemodynamic variables, myocardial blood flow, area at risk, or blood glucose between groups. Infarct size was markedly reduced in preconditioned dogs compared to control animals, at 7(SEM 2)% v 29(4)%, p