Sildenafil enhances central hemodynamic responses to exercise, but not VO2peak, in people with diabetes mellitus.

Roberts TJ; Burns AT; MacIsaac RJ; MacIsaac AI; Prior DL; La Gerche A;

Journal Of Applied Physiology (Bethesda, Md.: 1985) [J Appl Physiol (1985)] 2019 May 02. Date of Electronic Publication: 2019 May 02.

Exercise capacity is frequently reduced in people with diabetes mellitus (DM) and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM, and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semi-supine exercise echocardiography one hour after placebo or sildenafil ingestion in a double-blind randomized cross-over design. The primary efficacy end-point was exercise capacity (VO2peak) whilst secondary measures included pulmonary vascular resistance, cardiac output and change in PTAC. DM subjects were aged 44 ± 13 years, 73% male, with 16 ± 10 years’ DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4 ±1.2bpm P=0.04) and cardiac output (+322 ±21 ml, P=0.03) improved. However, the degree of PTAC did not change (P=0.93) and VO2max did not increase following sildenafil as compared to placebo (VO2peak 31.8 ±9.7 vs. 32.1 ±9.5 ml/min/kg, P=0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction.