1. ¹Cardiopulmonary Unit, Cardiology Division, University of Milano, San Paolo Hospital, Milano, Italy
2. ²Institute of Internal Medicine, University of Milano, Milano, Italy
3. ³Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano, Milano, Italy
4. ⁴Institute of Cardiology, University of Milano, Milano, Italy

Correspondence: M Guazzi, (marco.guazzi@unimi.it)

Received 14 April 2007; Accepted 4 June 2007; Published online 25 July 2007.

Abstract

Reflex neural oversignaling sensitive to muscle by-products (ergoreflex) causes exercise hyperventilation in heart failure (HF). We probed whether an improved endothelial function with sildenafil intake may prevent this effect. In 16 chronic heart failure patients and 16 normal subjects, before and after sildenafil intake (50 mg) or placebo, we measured ergoreflex, flow-mediated brachial artery dilation (FMD, an index of endothelial function), and, during maximal exercise, the slope of ventilation to carbon dioxide production (VE/VCO₂, an index of ventilatory efficiency), the ratio of changes in O₂ uptake (VO₂) versus work rate (WR) (VO₂/WR, an index of aerobic efficiency). After sildenafil intake, patients, unlike controls, showed a significant decrease in ergoreflex and VE/VCO₂ slope and an increase in FMD and VO₂/WR. Ergoreflex changes with sildenafil intake correlated with those in FMD and VE/VCO₂. Phosphodiesterase-5 inhibition, by improving endothelial activity and muscle perfusion, modulates signaling and improves ventilatory and aerobic efficiencies, potentially indicating a novel pathway in the HF therapeutic management.