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 posit ive inotropic agent, NKH477, 6-(3-dimethylaminopropionyl)forskolin hyd rochloride, a water-soluble derivative of forskolin, had deleterious e ffects on arrhythmias. NKH477 increased heart rate (HR) and decreased blood pressure (BP) in dogs with all the arrhythmia models. Unexpected ly, NKH477 suppressed digitalis- and epinephrine-induced arrhythmias, but did not suppress two-stage coronary ligation arrhythmia or aggrava te it. These results indicate that NKH477, unlike other new positive i notropic agents such as amrinone, milrinone, sulmazole and vesnarinone , did not worsen these arrhythmias; thus, NKH477 may be a useful posit ive inotropic agent with little arrhythmogenic effect.