[Effects of forskolin on canine congestive heart failure]

Forskolin is a diterpene of the labdane family which activates adenylate cyclase. The effects of forskolin were investigated in a congestive heart failure (CHF) model that we newly established using anesthetized dogs. The model was made by the intramural injection of protease into the left ventricular free wall, saline loading, and dextran and methoxamine infusion. By this maneuver, aortic blood flow (AoBF) was decreased; left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular endodiastolic pressure (LVEDP) were markedly increased; and systemic blood pressure was unchanged. A bolus injection of 5.0 micrograms/kg forskolin reversed the hemodynamic findings of CHF. It reduced LAP (17.5----7.9 mmHg) (mean, N = 7), SVR (19980----10390 dyne sec/cm5), time constant T (90.7----59.2 msec) and LVEDP (22.8----16.8 mmHg); and it increased Vmax (2.32----2.82 l/sec) and AoBF (0.50----0.72 l/min). Forskolin improved the CHF mainly through its vasodilator and positive inotropic actions.