Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes

Wetter, Thomas J.; Xiang, Zhuzai; Sonetti, David A.; Haverkamp, Hans Christian; Rice, Anthony J.; Abbasi, Adnan; Meyer, Keith C.; Dempsey, Jerome A.

doi:10.1152/japplphysiol.01095.2001

Cited by 28 publications

(21 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is unlikely that the lower in the NEIAH subjects was due to prematurely terminating exercise, as they became equally acidaemic and had a respiratory exchange ratio over 1.05. Others have shown that airway reactivity and lung inflammatory mediators are not linked to EIAH in young healthy subjects (Wetter et al 2001, 2002). As such, this probably does not explain the discrepancy between groups.…”

Section: Discussionmentioning

confidence: 99%

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

Dominelli¹,

Foster²,

Dominelli

et al. 2013

The Journal of Physiology

View full text Add to dashboard Cite

Key points• By virtue of their smaller lung volumes and airway diameters, women develop more mechanical ventilatory constraints during exercise, which may result in increased vulnerability to hypoxaemia during exercise.• Hypoxaemia developed at all exercise intensities with varying patterns and was more common in aerobically trained subjects; however, some untrained women also developed hypoxaemia.• Mechanical respiratory constraints directly lead to hypoxaemia in some women and prevent adequate reversal of hypoxaemia in most women.• Experimentally reversing mechanical constraints with heliox gas partially reversed the hypoxaemia in subjects who developed expiratory flow limitation.• Due in part to increased mechanical ventilatory constraints, the respiratory system's response to exercise is less than ideal in most women. AbstractThe purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension (P aO 2 ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption (V O 2 max ) = 49 ± 1, range 28-62 ml kg −1 min −1 ) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (∼85%V O 2 max ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation (S aO 2 ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir P aO 2 and S aO 2 ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, P aO 2 was inversely related toV O 2 max (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greaterV O 2 max (51 ± 1 vs. 43 ± 2 ml kg −1 min −1 ), lower end-exercise S aO 2 (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min −1 ), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mech...

show abstract

Section: Discussionmentioning

confidence: 99%

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

Dominelli¹,

Foster²,

Dominelli

et al. 2013

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…According to the pulmonary injury evoked airway inflammatory mediator release hypothesis (Pre´faut et al 1997(Pre´faut et al , 2000, an exaggeration of the arterial hypoxemia would be expected with increasing exercise duration as structural changes in the blood-gas barrier (Schaffartzik et al 1993;West et al 1993) intensify over time. Despite considerable appeal of this hypothesis (Pre´faut et al 1997(Pre´faut et al , 2000, the findings of Wetter et al (2001Wetter et al ( , 2002 in exercising human subjects did not lend credence to it. Similarly, pretreatment of thoroughbred horses with dexamethasone for 3 days to suppress the airway inflammatory response, and with a potent antihistaminic agent (H1-receptor antagonist, tripelennamine HCl) to mitigate the effects of airway inflammatory/mast cell released histamine on pulmonary capillary permeability also did not support the pulmonary injury hypothesis for exercise-induced arterial hypoxemia in racehorses (Manohar et al 2002a, b).…”

Section: Discussionmentioning

confidence: 95%

Acute hypervolemia does not improve arterial oxygenation in maximally exercising thoroughbred horses

2004

View full text Add to dashboard Cite

Recently, it was reported that acute hypervolemia improves arterial oxygen tension in human athletes known to experience exercise-induced arterial hypoxemia. Since exercise-induced arterial hypoxemia is routinely observed in racehorses and is known to limit performance, we examined whether pre-exercise induction of acute hypervolemia would similarly benefit arterial oxygenation in maximally exercising thoroughbred horses. Two sets of experiments, namely, placebo [intravenous (IV) physiological saline] and acute hypervolemia (IV 7.2% NaCl, causing an 18.2% expansion of plasma volume) studies were carried out in random order on 13 healthy, exercise-trained thoroughbred horses, 7 days apart. An incremental exercise protocol leading to 120 s of galloping at 14 m s(-1) on a 3.5% uphill incline was used. Galloping at this workload elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. In the placebo study, arterial oxygen tension decreased to 76.1 (2) mmHg (P<0.0001) at 30 s of maximal exertion, but further significant changes did not occur as exercise duration increased to 120 s [arterial oxygen tension 72.4 (2) mmHg]. A significant arterial hypoxemia also developed in galloping horses in the acute hypervolemia study [arterial oxygen tension at 30 and 120 s was 76.7 (1.7) and 71.9 (1.6) mmHg, respectively], but significant differences between treatments could not be demonstrated. In both treatments, a similar desaturation of arterial hemoglobin was also observed at 30 s of maximal exercise, which intensified with increasing exercise duration as hyperthermia, acidosis and hypercapnia intensified. Thus, acute expansion of plasma volume did not benefit arterial oxygenation in maximally exercising thoroughbred horses.

show abstract

“…8 12 13 However, nedocromil sodium was found to have no effect on pulmonary gas exchange in aerobically fit men and women when administered in conjunction with fexofenadine hydrochloride (a peripheral H 1 receptor antagonist) and zileuton (a leukotriene inhibitor). 10 A recent study has examined the effects of a single dose of a long or short acting ß 2 agonist (formoterol and salbutamol respectively) on trained non-asthmatic subjects during cycle ergometer exercise to exhaustion. 9 No significant differences were found for any maximal exercise variables (workload, VO 2 , VE, and SaO 2 ) between the two drugs or the placebo condition.…”

Section: Discussionmentioning

confidence: 99%

“…8 Anti-inflammatory drugs have been administered immediately before exercise, and the effects on EIAH observed. [8][9][10] To our knowledge, a combination of bronchodilators and corticosteroid drugs, used daily to suppress lung inflammation and reverse bronchoconstriction, has not been used to attenuate EIAH in athletes who experience this condition. Fluticasone is a corticosteroid that inhibits production of inflammatory cells (mast cells, basophils, lymphocytes) and cytokines.…”

mentioning

confidence: 99%

Effects of inhaled bronchodilators and corticosteroids on exercise induced arterial hypoxaemia in trained male athletes

et al. 2005

View full text Add to dashboard Cite

Objectives: To determine the effect of prophylactic treatment with an inhaled bronchodilator and antiinflammatory on arterial saturation (SaO 2 ) in trained non-asthmatic male athletes with exercise induced arterial hypoxaemia (EIAH). Methods: Nine male athletes (mean (SD) age 26.3 (6.7) years, height 182.6 (7.9) cm, weight 79.3 (10.5) kg, VO 2 MAX 62.3 (6.3) ml/kg/min, SaO 2 MIN 92.5 (1.1)%) with no history of asthma were tested in two experimental conditions. A combination of a therapeutic dose of salbutamol and fluticasone or an inert placebo was administered in a randomised crossover design for seven days before maximal cycling exercise. Oxygen consumption (VO 2 ), ventilation (VE), heart rate (HR), power output, and SaO 2 were monitored during the exercise tests. Results: There were no significant differences between the drug (D) and placebo (P) conditions for minimal SaO 2 (D = 93.6 (1.4), P = 93.0 (1.1)%; p = 0.93) VO 2 MAX (D = 61.5 (7.2), P = 61.9 (6.3) ml/kg/min; p = 0.91), peak power (D = 444.4 (48.3), P = 449.4 (43.9) W; p = 0.90), peak VE (D = 147.8 (19.1), P = 149.2 (15.5) litres/min; p = 0.82), or peak heart rate (D = 182.3 (10.0), P = 180.8 (5.5) beats/ min; p = 0.76). Conclusions: A therapeutic dose of salbutamol and fluticasone did not attenuate EIAH during maximal cycling in a group of trained male non-asthmatic athletes.H istorically, 50% of highly trained male athletes 1 and a greater number of female athletes 2 develop exercise induced arterial hypoxaemia (EIAH) during maximal exercise. These athletes, unable to maintain arterial oxygen saturation (SaO 2 ), show decreases in indicators of endurance performance 3 and a reduced maximal aerobic capacity. 4 These observations have fuelled research over the last two decades to investigate the possible mechanisms, which include intrapulmonary shunting of blood, relative alveolar hypoventilation, ventilation perfusion inequality, and pulmonary diffusion limitations. 5 These mechanisms have attracted a great deal of attention but the underlying causes of EIAH have yet to be completely understood. 5It has been documented that athletes unable to maintain SaO 2 show hindered physical performance in terms of decreased maximal aerobic capacity 4 and physical working capacity. 3In this study, the response to asthma inhaler medication was examined in normal subjects assumed to be nonasthmatic. Subjects with asthma have increased inflammation of the lung, and compromised ventilation secondary to bronchoconstriction is common. The standard of care for these patients is the administration of inhaled corticosteroids and bronchodilators. These drugs are effective in reversing airway obstruction and reducing lung inflammation, which allows asthmatics to perform sport and physical activity similar to normal, healthy people.Strenuous exercise, in asthmatic and non-asthmatic athletes, initiates an acute inflammatory response with leucocytosis, neutrophil activation, and release of inflammatory mediators and acute phase proteins. 6 Mediators of airway or vascular t...

show abstract

Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes

Cited by 28 publications

References 58 publications

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

Exercise‐induced arterial hypoxaemia and the mechanics of breathing in healthy young women

Acute hypervolemia does not improve arterial oxygenation in maximally exercising thoroughbred horses

Effects of inhaled bronchodilators and corticosteroids on exercise induced arterial hypoxaemia in trained male athletes

Contact Info

Product

Resources

About