Effect of Inhaled Nitric Oxide on Exercise Capacity and Pulmonary Gas Exchange in Adult Survivors of Preterm Birth

Abstract

RATIONALEPreterm birth affects millions of infants each year, and survival rates are on the rise. Frequently, premature birth results in alveolar simplification that may persist into adulthood. We have previously shown that pulmonary gas exchange efficiency is lower during exercise in some adults born preterm compared with control subjects. However, it is unknown whether the presence of inhaled nitric oxide (iNO), a potent broncho‐ and vasodilator, has an effect on pulmonary gas exchange and other physiological measures during exercise in preterm birth survivors. The objective of this study was to determine the effect of iNO on alveolar to arterial oxygen difference (AaO2), respiratory exchange ratio (RER), and maximum wattage during exercise in adult survivors of preterm birth.METHODSFourteen young adults born preterm (recruited from the Newborn Lung Project, birth weight <1,500 g, gestational age <36wk, age 20–23 years) and 16 term‐born, age‐matched control subjects performed incremental exercise on a cycle ergometer to volitional exhaustion while breathing normoxic air with and without iNO. Arterial and venous blood samples were taken every two minutes. Ventilation, mixed expired gases, power output, and oxygen consumption were continuously measured during rest and exercise using LabChart. Max wattage, RER, and AaO2 were calculated. Statistics were done with two‐way ANOVA to compare control and preterm with and without iNO with Tukey's for multiple comparisons.RESULTSWith respect to max power, controls attained a higher wattage than preterms in normoxia (p= 0.01). This difference was attenuated in the presence of iNO (174.3 ± 28.4 W controls without iNO v 141.4 ± 27.2 W preterms with iNO, p = 0.21). With respect to RER, there was no significant difference between controls and preterms in normoxia. In the presence of iNO, preterms had a significantly higher RER than controls without iNO throughout graded exercise (0.92 ± 0.10 v 0.89 ± 0.12, p = 0.0013). Preterms had a significantly higher AaO2 than controls during graded exercise in normoxia without iNO, which was attenuated with iNO (9.3 ±6.1 mmHg control v 11.6 ±10.8 mmHg preterm, p =0.21).CONCLUSIONSWe have previously shown that pulmonary gas exchange efficiency is lower in some adult survivors of preterm birth during exercise compared with control subjects. Here we show that iNO in preterm adults attenuates many of the metabolic and pulmonary gas exchange differences between preterm and control adults during graded exercise, including AaO2 and max power. RER in the preterm + NO group was significantly higher than the controls without NO. Overall, this suggests iNO can improve gas exchange efficiency in preterm born young adults.Support or Funding InformationNIH NHLBI, R01 HL086897 (Eldridge)Nitric oxide was supplied by Mallinckrodt Pharmaceuticals, formerly Ikaria, Inc.