Nedocromil sodium and diphenhydramine HCl ameliorate exercise‐induced arterial hypoxemia in highly trained athletes

• Published in: Physiological reports Vol. 10; no. 1; pp. e15149 - n/a
• Main Authors: Coyle, Michael A., Goss, Curtis S., Manz, Wesley J., Greenshields, Joel T., Chapman, Robert F., Stager, Joel M.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2022; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Aerosols; Alveoli; Athletes; blood‐gas barrier; Carbon dioxide; Diphenhydramine; Diphenhydramine - therapeutic use; Edema; Exercise; Exercise - physiology; Exercise Test; Fitness equipment; gas exchange; Gases; Heart rate; Histamine; Humans; Hyperventilation; Hypoxemia; Hypoxia - drug therapy; Inflammation; interstitial pulmonary edema; Laboratories; Male; Nedocromil - therapeutic use; Original; Oxygen; Oxygen Consumption - physiology; Permeability; Physiology; Ventilation; Young Adult; Indiana; United States > US; interstitial pulmonary edema; histamine; blood-gas barrier; gas exchange
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.15149

Introduction Exercise‐induced arterial hypoxemia (EIAH) has been observed in highly trained endurance athletes during near maximal exercise, which may be influenced by a histamine‐mediated inflammatory response at the pulmonary capillary‐alveolar membrane. In order to test this hypothesis, we examined whether the mast cell stabilizer nedocromil sodium (NS) and H1‐receptor antagonist diphenhydramine HCL (DH) would ameliorate EIAH and mitigate the drop in arterial oxyhemoglobin saturation (SaO2) during intensive exercise. Methods Seven highly trained male cross country runners (age, 21 ± 2 years; V̇O2max, 74.7 ± 3.5 ml·kg−1·min−1) participated in the study. All subjects completed a maximal exercise treadmill test to exhaustion, followed by three 5‐min constant‐load exercise bouts at 70%, 80%, and 90% V̇O2max. Prior to testing, subjects received either placebo (PL), NS, or DH. Results Compared to PL, there was a significant treatment effect on SaO2 (p < 0.001) for both NS and DH during both constant‐load exercise and at V̇O2max. Post hoc tests revealed SaO2 values, compared to PL, were significantly higher at V̇O2max and during DH trials and higher with NS at constant‐load intensities except at 70% (p = 0.13). Conclusion The findings provide further evidence that histamine contributes directly or indirectly to the development of EIAH during intense exercise in highly trained athletes. The etiology of EIAH is currently unclear and likely idiopathic, and the theory that a histamine‐mediated inflammatory response may contribute to this phenomenon in some individuals merits further investigation. To our knowledge, the present study is the first to examine this theory in a group of athletes all with V̇O2max values >70 ml·kg−1·min−1, while adding to the relatively sparse body of literature examining EIAH in cohorts of this training status. Our findings indicate that, at least in this cohort of highly trained runners with superior V̇O2max values, pharmacological inhibition of the histamine response mitigated the decline in SaO2 without any change in ventilation, supporting previous literature which suggests that histaminergic release and action are related to the observed decrease in SaO2 during exercise.