Furthermore, PKA phosphorylates and deactivates the phospholambans that inhibit SERCA, which is an enzymatic pump that, to terminate the contraction, removes the Ca2+ from the cytoplasm, stores it back in the sarcoplasmic reticulum and promotes the subsequent arterial relaxation as well, producing a lusitropic effect.

Amrinone also has beneficial effects during diastole in the left ventricle, including relaxation, compliance and filling in patients with congestive heart failure.

Congestive heart failure (CHF) is characterized by a reduction in ventricular performance and abnormalities in peripheral circulation and organs.

[6] A reduced release of endothelium derived relaxing factor (EDRF) causes a decrease in the stimulation of guanylate cyclase, and cyclic GMP (cGMP) levels fall in vascular smooth muscle.

[6] Patients with CHF have a down-regulation of their β-1 adrenergic receptors which alters their ability to activate intracellular adenylate cyclase, which catalyzes cAMP formation.

An IV administration of amrinone has been shown to increase cardiac output (CO) and stroke volume (SV), while concurrently reducing the filling pressure of the left ventricle and decreasing the resistance in the peripheral vasculature.

[2][8][9] The improvement in performance of the ventricles is likely to result from a direct stimulation of the depressed myocardium as well as a decrease in peripheral vascular resistance.

Early studies in patients with heart failure showed that amrinone produced short-term hemodynamic improvement, but had limited long-term clinical benefit.