The Effect of Inhaled Nitric Oxide on Maximal Oxygen Consumption During Exercise in Hypoxia.

• Author / Creator

  Rampuri, Zahrah Hatimali

• Background and Rationale. Arterial hypoxemia (decreased arterial oxygen content [CaO2]) caused by a decrease in inspired partial pressure of oxygen (PIO2), can result in a similar reduction in exercise capacity as observed in chronic lung disease. Literature has suggested a discrepancy in the effect of increasing hypoxic severity on peak cardiac output (Q̇) and therefore exercise capacity (V̇O2max). In moderate hypoxia (PIO2≥85mmHg), V̇O2max decline has been attributed to arterial desaturation, whereas in severe hypoxia (PIO2<85mmHg), impaired peak Q̇, secondary to elevated pulmonary artery pressure (PAP) has been suggested to play a role. Inhaled nitric oxide (iNO) reduces PAP at rest and during exercise in normoxia, and therefore could be used as a tool to evaluate the impact of reducing PAP during hypoxic exercise on Q̇ and V̇O2max.
  Purpose and Hypothesis. The purpose of this study was to better understand the mechanism(s) of exercise intolerance and cardiovascular regulation in hypoxia, by determining if the elevation in PAP in hypoxia is a limiting factor of V̇O2max. It was hypothesized that iNO would improve V̇O2max during exercise in both moderate and severe hypoxia by reducing PAP, leading to increased SV and peak Q̇. Further, it was hypothesized that the magnitude of improvement in V̇O2max with iNO would be smaller in severe hypoxia due to an underlying diffusion limitation in severe hypoxia which would limit the increase in V̇O2max from augmenting Q̇.
  Methods. Twelve young, healthy participants with normal lung function were recruited. Participants completed 6 sessions: visit 1) pulmonary function test and normoxic cardiopulmonary exercise test (CPET); visits 2-5) experimental CPETs on separate days breathing the following conditions: A) moderate hypoxia, B) severe hypoxia, C) moderate hypoxia with iNO, and D) severe hypoxia with iNO (order randomized); visit 6) resting and exercise cardiac ultrasound trial while breathing the conditions listed above in a randomized order. V̇O2, ventilation [V̇E], carbon dioxide production [V̇CO2], ventilatory equivalent to carbon dioxide production [V̇E/V̇CO2], partial pressure of end-tidal carbon dioxide [PETCO2]) were measured using a metabolic measurement system. Q̇ was estimated using impedance cardiography and right ventricular systolic pressure (RVSP) was estimated via Doppler echocardiography.
  Results. V̇O2max was decreased by 0.43±0.07 L/min in moderate hypoxia (p=0.005) and 0.78±0.12 L/min in severe hypoxia (p<0.001) when compared to normoxia. iNO reduced resting RVSP by 2.53±0.8 mmHg in moderate hypoxia (p=0.01) and 1.78±0.2 mmHg in severe hypoxia (p=0.05), however, iNO had no effect on V̇O2max in either hypoxic level. Furthermore, peak Q̇ was unaffected by hypoxia or iNO.
  Discussion and Significance. These findings suggest that the hypoxia-induced increase in PAP does not impair peak Q̇ and therefore V̇O2max in healthy participants during hypoxic exercise. This study demonstrated that the pulmonary vasculature and right ventricle likely do not limit hypoxic exercise in healthy individuals suggesting that in hypoxemic patients, the pulmonary vasculature may not directly impair exercise capacity. This work highlights the importance of further understanding mechanism(s) and treatments of exercise limitations in hypoxemic patients, as improving exercise capacity would increase participation in meaningful activities of daily living, and subsequently quality of life. These findings may suggest that the pulmonary hypertension associated with chronic lung disease does not directly impact exercise tolerance.

• Subjects / Keywords

  • Inhaled nitric oxide
  • Hypoxia
  • Maximal oxygen consumption
  • Health
  • Right ventricular systolic pressure
  • Cardiac output
  • Wagner model

• Graduation date

  Fall 2021

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-ws22-j394

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.