Novel role of phosphodiesterase inhibitors in the management of end-stage heart failure

Figure 3 Concomitant use of beta blocker and milrinone causes inhibition of G inhibitory alpha protein which is an inhibitor of adenylyl cyclase and phosphodiesterase III enzyme, both results in increased cyclic adenosine monophosphate concentration. Increased cAMP inhibits phospholamban (PLB) resulting in efficient movement of calcium (Ca²⁺) from cytosol into the SR through sarcoplasmic reticulum calcium ATPase (SERCA). This PLB mediated Ca²⁺ handling results in improved systolic and diastolic function. In addition, BB inhibits beta-adrenoreceptor (βAR) mediated increased Ca²⁺ influx through L-type calcium channel (LTCC) that is associated with increased arrhythmogenicity. ATP: Adenosine triphosphate; cAMP: Cyclic adenosine monophosphate; Gαi: G inhibitory alpha protein; Gαs: G stimulatory alpha protein; PDE: Phosphodiesterase; SNS: Sympathetic nervous system; BB: Beta blocker; AC: Adenylyl cyclase.