Effect of NKH477, a New Water-Soluble Forskolin Derivative, on Arterial-Ventricular Coupling and Mechanical Energy Transduction in Patients with Left Ventricular Systolic Dysfunction

Abstract

We examined the effects of a novel water-soluble forskolin derivative, NKH477 (0.5 microgram/kg/min), on arterial-ventricular (A-V) coupling and mechanical energy transduction from heart to circulatory bed in comparison with those of dobutamine (3 micrograms/kg/min) in 8 patients with left ventricular (LV) systolic dysfunction using a conductance catheter method. A-V coupling was assessed as the ratio of the effective arterial elastance (E(a)) to the slope of the end-systolic pressure-volume relation (ESPVR) (E(max), left ventricular contractility index), and the ratio of mechanical energy transduction was obtained as the fraction of PV area (PVA) comprised of stroke work (SW). E(max) (2.59 mm Hg/ml/m2), E(a)/E(max) (1.62), and SW/PVA (0.58) were impaired in control contractile state. NKH477 increased Emax to the same extent as dobutamine. E(a) decreased with NKH477 but not with dobutamine. As a consequence, the decrease in E(a)/E(max) with NKH477 was greater than that with dobutamine (52 vs. 47%, p < 0.05); the increase in SW/PVA with NKH477 was also greater than that with dobutamine (28 vs. 21%, p < 0.05). These findings suggest that NKH477 may be a superior alternative to dobutamine in A-V coupling and mechanical energy transduction in patients with LV systolic dysfunction.