In the present experiment, inhibition of cGMP-efflux is achieved at supratherapeutic concentrations during both normothermia and hypothermia, while PDE5 inhibition by sildenafil or vardenafil, appears a promising strategy to achieve physiologically balanced afterload reduction, and prevent pulmonary edema in hypothermic VA-ECMO patients (Lo Coco et al., 2018). The gene discussed is PDE5A; the disease is pulmonary edema.