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.