Effects of a new forskolin derivative, NKH477, on canine ventricular arrhythmia models.
Using two-stage coronary ligation-, digitalis- and epinephrine-induced canine ventricular arrhythmia models, we examined whether a new positive inotropic agent, NKH477, 6-(3-dimethylaminopropionyl)forskolin hydrochloride, a water-soluble derivative of forskolin, had deleterious effects on arrhythmias. NKH477 increased heart rate (HR) and decreased blood pressure (BP) in dogs with all the arrhythmia models. Unexpectedly, NKH477 suppressed digitalis- and epinephrine-induced arrhythmias, but did not suppress two-stage coronary ligation arrhythmia or aggravate it. These results indicate that NKH477, unlike other new positive inotropic agents such as amrinone, milrinone, sulmazole and vesnarinone, did not worsen these arrhythmias; thus, NKH477 may be a useful positive inotropic agent with little arrhythmogenic effect.
Hirasawa
A
A
Department of Pharmacology, Yamanashi Medical University, Japan.
Awaji
T
T
Hosono
M
M
Haruno
A
A
Hashimoto
K
K
D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects*; D005576:Colforsin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D014665:Vasodilator Agents; D005576:Colforsin; D010042:Ouabain; D004837:Epinephrine