The effect of inhaled nitric oxide on maximal oxygen consumption during exercise in acute hypoxia: a randomized double-blind crossover trial.

In moderate hypoxia [partial pressure of inspired oxygen ([Formula: see text]) = 85-111 mmHg], the reduction in maximal oxygen consumption (V̇o2max) has been attributed to arterial desaturation, whereas in severe hypoxia ([Formula: see text] < 85 mmHg), elevated pulmonary artery pressure (PAP) is thought to impair peak cardiac output ([Formula: see text]) and therefore V̇o2max. The purpose of this study was to examine whether reducing PAP with inhaled nitric oxide (iNO, a selective pulmonary vasodilator) would increase V̇o2max in moderate and severe acute hypoxia. Twelve young, healthy participants (mean V̇o2max = 45.3 ± 12.2 mL/kg/min), with normal lung function completed the randomized double-blind crossover study over six sessions. Experimental cardiopulmonary exercise tests (CPET) were completed on separate days with participants under the following conditions: 1) acute moderate hypoxia ([Formula: see text] = 89 mmHg), 2) acute severe hypoxia ([Formula: see text] = 79 mmHg), 3) acute moderate hypoxia with 40 ppm iNO, and 4) acute severe hypoxia with 40 ppm iNO (order randomized). On separate days, rest, and exercise (60 W), echocardiography was conducted to determine right ventricular systolic pressure (RVSP/PAP) under conditions 1-4. Resting RVSP was reduced by 2.5 ± 0.8 mmHg with iNO in moderate hypoxia (P = 0.01) and 1.8 ± 0.2 mmHg in severe hypoxia (P = 0.05); however, iNO had no effect on peak [Formula: see text] or V̇o2max in either hypoxic condition. Despite reducing RVSP with iNO in hypoxia, peak [Formula: see text] and V̇o2max were unaffected, suggesting that iNO may not improve exercise tolerance in healthy participants during hypoxic exercise.NEW & NOTEWORTHY The elevation of pulmonary artery pressure (PAP) with hypoxia may impair peak cardiac output ([Formula: see text]) and therefore V̇o2max. Our novel findings show that despite reducing resting RVSP in acute moderate ([Formula: see text] = 89 mmHg) and severe hypoxia ([Formula: see text] = 79 mmHg) with inspired nitric oxide, peak [Formula: see text], and V̇o2max were unaffected.

Blood glucose concentration is unchanged during exposure to acute normobaric hypoxia in healthy humans.

Normal blood [glucose] regulation is critical to support metabolism, particularly in contexts of metabolic stressors (e.g., exercise, high altitude hypoxia). Data regarding blood [glucose] regulation in hypoxia are inconclusive. We aimed to characterize blood [glucose] over 80 min following glucose ingestion during both normoxia and acute normobaric hypoxia. In a randomized cross-over design, on two separate days, 28 healthy participants (16 females; 21.8 ± 1.6 years; BMI 22.8 ± 2.5 kg/m2 ) were randomly exposed to either NX (room air; fraction of inspired [FI ]O2 ~0.21) or HX (FI O2 ~0.148) in a normobaric hypoxia chamber. Measured FI O2 and peripheral oxygen saturation were both lower at baseline in hypoxia (p < 0.001), which was maintained over 80 min, confirming the hypoxic intervention. Following a 10-min baseline (BL) under both conditions, participants consumed a standardized glucose beverage (75 g, 296 ml) and blood [glucose] and physiological variables were measured at BL intermittently over 80 min. Blood [glucose] was measured from finger capillary samples via glucometer. Initial fasted blood [glucose] was not different between trials (NX:4.8 ± 0.4 vs. HX:4.9 ± 0.4 mmol/L; p = 0.47). Blood [glucose] was sampled every 10 min (absolute, delta, and percent change) following glucose ingestion over 80 min, and was not different between conditions (p > 0.77). In addition, mean, peak, and time-to-peak responses during the 80 min were not different between conditions (p > 0.14). There were also no sex differences in these blood [glucose] responses in hypoxia. We conclude that glucose regulation is unchanged in young, healthy participants with exposure to acute steady-state normobaric hypoxia, likely due to counterbalancing mechanisms underlying blood [glucose] regulation in hypoxia.

Ventilatory efficiency in athletes, asthma and obesity.

During submaximal exercise, minute ventilation (V' E) increases in proportion to metabolic rate (i.e. carbon dioxide production (V' CO2 )) to maintain arterial blood gas homeostasis. The ratio V' E/V' CO2 , commonly termed ventilatory efficiency, is a useful tool to evaluate exercise responses in healthy individuals and patients with chronic disease. Emerging research has shown abnormal ventilatory responses to exercise (either elevated or blunted V' E/V' CO2 ) in some chronic respiratory and cardiovascular conditions. This review will briefly provide an overview of the physiology of ventilatory efficiency, before describing the ventilatory responses to exercise in healthy trained endurance athletes, patients with asthma, and patients with obesity. During submaximal exercise, the V' E/V' CO2 response is generally normal in endurance-trained individuals, patients with asthma and patients with obesity. However, in endurance-trained individuals, asthmatics who demonstrate exercise induced-bronchoconstriction, and morbidly obese individuals, the V' E/V' CO2 can be blunted at maximal exercise, likely because of mechanical ventilatory constraint.

Cardiorespiratory hysteresis during incremental high-altitude ascent-descent quantifies the magnitude of ventilatory acclimatization.

NEW FINDINGS: What is the central question of this study? We assessed the utility of a new metric for quantifying ventilatory acclimatization to high altitude, derived from differential ascent and descent steady-state cardiorespiratory variables (i.e. hysteresis). Furthermore, we aimed to investigate whether the magnitude of cardiorespiratory hysteresis was associated with the development of acute mountain sickness. What is the main finding and its importance? Hysteresis in steady-state cardiorespiratory variables quantifies ventilatory acclimatization to high altitude. The magnitude of cardiorespiratory hysteresis during ascent to and descent from high altitude was significantly related to the development of symptoms of acute mountain sickness. Hysteresis in steady-state chemoreflex drive can provide a simple, non-invasive method of tracking ventilatory acclimatization to high altitude. ABSTRACT: Maintenance of arterial blood gases is achieved through sophisticated regulation of ventilation, mediated by central and peripheral chemoreflexes. Respiratory chemoreflexes are important during exposure to high altitude owing to the competing influence of hypoxia and hypoxic hyperventilation-mediated hypocapnia on steady-state ventilatory drive. Inter-individual variability exists in ventilatory acclimatization to high altitude, potentially affecting the development of acute mountain sickness (AMS). We aimed to quantify ventilatory acclimatization to high altitude by comparing differential ascent and descent values (i.e. hysteresis) in steady-state cardiorespiratory variables. We hypothesized that: (i) the hysteresis area formed by cardiorespiratory variables during ascent and descent would quantify the magnitude of ventilatory acclimatization; and (ii) larger hysteresis areas would be associated with lower AMS symptom scores during ascent. In 25 healthy, acetazolamide-free trekkers ascending to and descending from 5160 m, cardiorespiratory hysteresis was measured in the partial pressure of end-tidal CO2 , peripheral oxygen saturation, minute ventilation, chemoreceptor stimulus index (end-tidal CO2 /peripheral oxygen saturation) and the calculated steady-state chemoreflex drive (SS-CD; minute ventilation/chemoreceptor stimulus index) using portable devices (capnograph, peripheral pulse oximeter and respirometer, respectively). Symptoms of AMS were assessed daily using the Lake Louise questionnaire. We found that: (i) ascent-descent hysteresis was present in all cardiorespiratory variables; (ii) SS-CD is a valid metric for tracking ventilatory acclimatization to high altitude; and (iii) the highest AMS scores during ascent exhibited a significant, moderate and inverse correlation with the magnitude of SS-CD hysteresis (rs  = -0.408, P = 0.043). We propose that ascent-descent hysteresis is a new and feasible way to quantify ventilatory acclimatization in trekkers during high-altitude exposure.

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea.

NEW FINDINGS: What is the central question of this study? What is the relative contribution of a putative tonic splenic contraction to the haematological acclimatization process during high altitude ascent in native lowlanders? What is the main finding and its importance? Spleen volume decreased by -14.3% (-15.2 ml) per 1000 m ascent, with an attenuated apnoea-induced [Hb] increase, attesting to a tonic splenic contraction during high altitude ascent. The [Hb]-enhancing function of splenic contraction may contribute to restoring oxygen content early in the acclimatization process at high altitude. ABSTRACT: Voluntary apnoea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in haemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation ( SpO2 ), which may cause tonic splenic contraction, which may contribute to haematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, SpO2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0) to 3440 m (day 3), 4240 m (day 7) and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnoea-induced responses in HR, SpO2 and splenic volume were measured before and after two separate voluntary maximal apnoeas (A1-A2) at 1400, 3440 and 4240 m. Resting spleen volume decreased -14.3% (-15.2 ml) per 1000 m with ascent, from 140 ± 41 ml (1400 m) to 108 ± 28 ml (3440 m; P > 0.99), 94 ± 22 ml (4240 m; P = 0.009) and 84 ± 28 ml (5160 m; P = 0.029), with concomitant increases in [Hb] from 125 ± 18.3 g l-1 (1400 m) to 128 ± 10.4 g l-1 (3440 m), 138.8 ± 12.7 g l-1 (4240 m) and 157.5 ± 8 g l-1 (5160 m; P = 0.021). Apnoea-induced splenic contraction was 50 ± 15 ml (1400 m), 44 ± 17 ml (3440 m; P > 0.99) and 26 ± 8 ml (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnoea-induced bradycardia was more pronounced at 3440 m (A1: P = 0.04; A2: P = 0.094) and at 4240 m (A1: P = 0.037 A2: P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnoea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to haematological acclimatization early in HA ascent in humans.

Preservation of Neurovascular Coupling to Cognitive Activity in Anterior Cerebrovasculature During Incremental Ascent to High Altitude.

Background: High altitude sojourn challenges blood flow regulation in the brain, which may contribute to cognitive dysfunction. Neurovascular coupling (NVC) describes the ability to increase blood flow to working regions of the brain. Effects of high altitude on NVC in frontal regions undergoing cognitive activation are unclear but may be relevant to executive function in high-altitude hypoxia. This study sought to examine the effect of incremental ascent to very high altitude on NVC by measuring anterior cerebral artery (ACA) and middle cerebral artery (MCA) hemodynamic responses to sustained cognitive activity. Materials and Methods: Eight adults (23 ± 7 years, four female) underwent bilateral measurement of ACA and MCA mean velocity and pulsatility index (PI) through transcranial Doppler during a 3-minute Stroop task at 1400, 3440, and 4240 m. Results: Resting MCA and ACA PI decreased with high-altitude hypoxia (p < 0.05). Cognitive activity at all altitudes resulted in similar increases in MCA and ACA mean velocity, and decreases in ACA and MCA PI (p < 0.05 for MCA, p = 0.07 for ACA). No significant altitude-by-Stroop interactions were detected, indicating NVC was stable with increasing altitude. Conclusions: Ascent to very high altitude (4240 m) using an incremental profile that supports partial acclimatization does not appear to disturb (1) increases in cerebral blood velocity and (2) reductions in pulsatility that characterize optimal NVC in frontal regions of the brain during cognitive activity.