Peripheral and pulmonary effects of inorganic nitrite during exercise in heart failure with preserved ejection...

To determine whether inorganic nitrite improves peripheral and pulmonary oxygen (O₂ ) transport during exercise in heart failure with preserved ejection fraction (HFpEF).

Data from two invasive, randomized, double-blind, placebo-controlled trials with matched workload exercise of inhaled and intravenous sodium nitrite were pooled for this analysis (n = 51). Directly measured O₂ consumption (VO₂ ) and blood gas data were used to evaluate the effect of nitrite on skeletal muscle O₂ conductance (Dm), VO₂ kinetics, alveolar capillary membrane O₂ conductance (D_L ), and O₂ utilization during submaximal exercise. As compared to placebo, treatment with nitrite resulted in an improvement in Dm (+4.9 ± 6.5 vs. -0.9 ± 4.3 mL/mmHg*min, P = 0.0008) as well as VO₂ kinetics measured by mean response time (-5.0 ± 6.9 vs. -0.6 ± 6.0 s, P = 0.03), with preserved O₂ utilization despite increased convective O₂ delivery through cardiac output (+0.4 ± 0.7 vs. -0.3 ± 0.9 L/min, P = 0.02). Nitrite improved D_L (+2.5 ± 6.3 vs. -2.0 ± 9.0 mL/mmHg*min, P = 0.05) with exercise, which was associated with lower pulmonary capillary pressures (r = -0.34, P = 0.02), and reduced pulmonary dead space ventilation fraction (-0.01 ± 0.05 vs. +0.02 ± 0.05, P = 0.02).

Sodium nitrite enhances skeletal muscle Dm during exercise as well as pulmonary O₂ diffusion, optimizing O₂ kinetics in tandem with increased convective O₂ delivery through cardiac output augmentation. The favourable combined pulmonary, cardiac and peripheral effects of nitrite may improve exercise tolerance in people with HFpEF and requires further investigation.

ClinicalTrials.gov ID NCT01932606 and NCT02262078.