Effect of 8- (3-diethylaminopropyl) -6,6-dimethyl- (2-phenyl-1 H-imidazo (4,5 h) ) isoquinoline-7,9- (6H) -dione dihydrochloride (AR-LH31) on experimental cardiac arrhythmias in dogs
Kerr, M.J.; Harron, D.W.; Wilson, R.; Shanks, R.G.
Arzneimittel-Forschung 35(1a): 197-200
1985
ISSN/ISBN: 0004-4172 PMID: 3838674 Document Number: 264758
The effects of intravenously administered 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1H-imidazo (4,5H))-isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimentally induced ventricular tachycardia were studied in dogs. Ventricular tachycardia was produced in 6 anaesthetised dogs by the intravenous injection of ouabain (66.7 +/- 4.9 mg/kg). AR-LH31 administered by increasing bolus injections every 5 min completely suppressed the ventricular tachycardia with a return to sinus rhythm in 1 out of 6 dogs, with a partial return of sinus beats in a second dog. There was no return to sinus rhythm in the 4 remaining dogs after doses ranging from 1.75 to 15.75 mg/kg. Observations were made in 9 conscious dogs 22-24 hours after ligation of the anterior descending branch of the left coronary artery when a ventricular tachycardia was present. The administration of AR-LH31 by bolus intravenous injection in 4 dogs did not abolish the arrhythmia in any dog but increased the number of sinus beats. In 3 out of 4 dogs after a cumulative dose of 7.75 mg/kg, 60% of ventricular beats were of sinus origin. The effects of larger doses could not be studied be cause of adverse effects. In 5 dogs the administration of AR-LH31 by constant intravenous infusion at 16 mg/kg/h restored sinus rhythm in all dogs after a mean dose of 9.9 +/- 0.9 mg/kg. These studies indicate that AR-LH31 has anti-arrhythmic activity in dogs and highlight the importance of the method of administration in determining the effects of a drug.