Differential Cardiac versus Renal Response to Acute Volume Overload in Human Preclinical Systolic Dysfunction and Renal Dysfunction with the Combination of PDEV Inhibition and BNP Administration

Abstract

Preclinical systolic dysfunction (PSD) is defined by LVEF < 45% without symptoms of heart failure (HF) (Stage B HF). We have previously demonstrated that an impaired cardiorenal response to acute volume loading (AVL) exists in PSD. Type V phosphodiesterase (PDEV) metabolizes cGMP, second messenger of the B-type natriuretic peptide (BNP). Preclinical studies have demonstrated that PDEV inhibition (PVEVI) enhances the cardiorenal actions of BNP. The objective of the current study is to determine if the combination of PDEVI and BNP will result in a greater enhancement of the cardiorenal response to AVL as compared to PDEVI alone in PSD.