5-hydroxydecanoate fails to attenuate ventricular fibrillation in a conscious canine model of sudden cardiac death.
The electrophysiologic and antifibrillatory properties of 5-hydroxydecanoate, a KATP channel antagonist, were studied in a conscious canine model of sudden cardiac death. After a surgically induced myocardial infarction, animals were subjected to programmed electrical stimulation to identify those at risk for sudden cardiac death. 5-Hydroxydecanoate was administered as a bolus (10 mg/kg i.v.) followed by an infusion, 10 mg/kg/h (group 1, n = 12) or 30 mg/kg bolus followed by an infusion, 30 mg/kg/h (group 2, n = 8) i.v., while vehicle treated animals received a 0.9% sodium chloride solution (group 3, n = 11). The administration of 5-hydroxydecanoate did not alter the ventricular effective refractory period or the QTc interval. Anterior wall myocardial infarcts, expressed as a percentage of the left ventricle, did not differ among groups. Infusions of 5-hydroxydecanoate did not confer significant protection from sudden cardiac death (death within 60 min of posterolateral ischemia) due to ventricular fibrillation: group 1, 50%; group 2, 38%; and group 3, 18%. The data demonstrate that a continuous infusion of 5-hydroxydecanoate (10 and 30 mg/kg/h, i.v.) does not provide protection from ischemia-induced ventricular fibrillation in the postinfarcted conscious canine.
Friedrichs
G S
GS
University of Michigan Medical School, Department of Pharmacology, Ann Arbon 48109-0632, USA.
Abreu
J N
JN
Black
S C
SC
Chi
L
L
Lucchesi
B R
BR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D003652:Decanoic Acids / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007511:Ischemia / Q000139:chemically induced; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; C052853:5-hydroxydecanoic acid