Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure

Abstract

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure. Am J Physiol Heart Circ Physiol 303: H1474 –H1480, 2012. First published Sep tember 28, 2012; doi:10.1152/ajpheart.00435.2012.—Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O2) delivery (Q˙ O2mv) to O2 uptake (V˙ O2) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Q˙ O2mv-to-O2 utilization matching and V˙ O2 kinetics, 10 males with CHF (ejection fraction 27 6%) undertook constant work-rate exercise (70 – 80% peak). Breath-by breath V˙ O2, fractional O2 extraction in the vastus lateralis {deoxy genated hemoglobin myoglobin ([deoxy-Hb Mb]) by near infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by 20%, an effect that was related to faster on and off-exercise V˙ O2 kinetics (P 0.05). Active treatment, however, failed to accelerate CO dynamics (P 0.05). On-exercise [deoxy-Hb Mb] kinetics were slowed by sildenafil (25%), and a subsequent response “overshoot” (n 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb Mb] recovery was faster with sildenafil (15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise V˙ O2 kinetics, blunted oscillations in ventilation (n 9), and greater exercise capacity (P 0.05). Sildenafil intake enhanced intramuscular Q˙ O2mv-to-V˙ O2 matching with beneficial effects on V˙ O2 kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.