Effects of glyburide on ischemia-induced changes in extracellular potassium and local myocardial activation: a potential new approach to the management of ischemia-induced malignant ventricular arrhythmias.
The increase in extracellular potassium [K+]o levels during the early phase of myocardial ischemia may result in part from activation of adenosine triphosphate-sensitive K+ channels. Glyburide, a second-generation hypoglycemic sulfonylurea, is a potent blocker of these channels. We studied the effects of glyburide on [K+]o and on intramyocardial conduction delay during a 10-minute occlusion of the left anterior descending artery in the dog. K(+)-sensitive electrodes and bipolar plunge electrodes were introduced to record, respectively, [K+]o and local electrograms from close sites in midmyocardial regions in normal, border, and ischemic zones. Recordings were obtained before (control ischemia [CI]) and 20 minutes after intravenous administration of 0.15 mg/kg of glyburide (glyburide plus ischemia [G + I]). During G + I the extent of the increase in [K+]o was less compared to that during CI, and the difference was statistically significant during the first 7 minutes of ischemia in the ischemic zone and during the first 4 minutes of ischemia in the border zone. On the other hand, the degree of local intramyocardial conduction delay was significantly reduced during G + I compared to CI during the entire 10 minutes of ischemia in both the ischemic and border zones. In summary, our results have shown that glyburide significantly reduced the rise of [K+]o and intramyocardial delay during the early phase of acute ischemia and could thus attenuate the electrophysiologic consequences of ischemia that underlie the initial phase of malignant tachyarrhythmias. Although the effects of glyburide may result in part from a direct action of the drug on cardiac adenosine triphosphate-sensitive K+ channels, other metabolic antiischemic effects cannot be ruled out.
Bekheit
S S
SS
Department of Medicine, State University of New York, Brooklyn.
Restivo
M
M
Boutjdir
M
M
Henkin
R
R
Gooyandeh
K
K
Assadi
M
M
Khatib
S
S
Gough
W B
WB
el-Sherif
N
N
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004562:Electrocardiography; D005905:Glyburide / Q000097:blood / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*
D001786:Blood Glucose; D011188:Potassium; D005905:Glyburide