Coronary vascular K+ATP channels contribute to the maintenance of myocardial perfusion in dogs with pacing-induced heart failure.
The functional role of coronary vascular ATP-sensitive potassium (K+ATP) channels in the regulation of coronary blood flow (CBF) has not been determined in chronic heart failure (CHF). To test the hypothesis that K+ATP channels contribute to myocardial perfusion in HF, we examined the effects of intracoronary infusion of glibenclamide, an inhibitor of K+ATP channels, on basal CBF in control and CHF dogs. CHF was produced in mongrel dogs by pacing the right ventricle for 4 weeks. Under anesthesia, CBF in the left anterior descending coronary artery, other hemodynamic and metabolic parameters, or regional myocardial blood flow were measured. Basal CBF was less in CHF dogs than in controls. Glibenclamide at the graded doses (5, 15 and 50 microg x kg(-1) x min(-1) decreased CBF in both control and CHF dogs. The percentage decrease in CBF with glibenclamide at 50 microg x kg(-1) x min(-1) was greater (p<0.01) in CHF dogs than in controls. The greater decrease in CBF with glibenclamide at 50microg x kg(-1) x min(-1) was associated with myocardial ischemia. Glibenclamide decreased myocardial blood flow in each sublayer of the myocardium in the 2 groups. These results suggest that the basal activity of coronary vascular K+ATP channels is increased in CHF dogs but not in controls. This may contribute to the maintenance of myocardial perfusion in CHF.
Yamamoto
M
M
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Egashira
K
K
Arimura
K
K
Tada
H
H
Shimokawa
H
H
Takeshita
A
A
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000737:chemistry / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000209:etiology; D019335:Nitroarginine / Q000494:pharmacology; D010138:Pacemaker, Artificial; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000494:pharmacology / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D019335:Nitroarginine; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D005905:Glyburide