The effect of consistent practice of yogic breathing exercises on the human cardiorespiratory system.

The purpose of this investigation was to quantify the cardiovascular, respiratory, and cerebrovascular effects of two common yogic breathing exercises (YBE): bhastrika and chaturbhuj; and to determine the effect of their consistent practice on chemosensitivity. The first study was cross-sectional and compared experienced yogic breathers (YB) with matched controls; whereas the second was a 10-week longitudinal training study. The results support four major findings. First chaturbhuj resulted in a hypoxic stimulus in experienced YB compared to control [end-tidal oxygen tension (PETO2), YB: 77.5±5.7mmHg, P<0.05; control: 94.3±12.0mmHg]. Second, performance of chaturbhuj resulted in cyclic oscillations of mean arterial pressure (MAP), heart rate (HR), and middle cerebral artery velocity (MCAv) consistent with the phases of respiration. Third, post training, performance of bhastrika reduced PETO2 (end breath-hold: 90.8 8±12.1mmHg) compared to rest (100.1±7.4, P<0.05); it also resulted in significantly increased MAP at end breath-hold (96.7±13.0mmHg) compared to rest (83.0±6.6mmHg, P<0.05) and significantly increased mean MCAv (end breath-hold: 87.4±23.0cm/s, P<0.05; rest: 55.8±26.3cm/s). Fourth, experienced YB had lower central chemosensitivity than controls (YB: 3.4±0.4; control: 4.6±1.2L/min/mmHg; P<0.05). In conclusion, YBE significantly alter end-tidal gases, resulting in complex oscillations of cardiovascular and cerebrovascular variables, and if practiced consistently, may reduce chemosensitivity.

Cerebrovascular Response to CO2 Following 10 Days of Intermittent Hypoxia in Humans.

INTRODUCTION: It has been demonstrated that the cerebrovascular response to hypoxia is blunted following 10 d of intermittent hypoxia (IH) in healthy humans. The purpose of this study was to test the hypothesis that IH reduces the cerebrovascular response to CO2. METHODS: Healthy male subjects (N=8; 25±2 yr) were exposed to 10 consecutive days of IH (12% O2 for 5 min followed by 5 min of normoxia for 1 h/d). The cerebrovascular response to CO2 was assessed prior to (PRE-IH) and following (POST-IH) the IH paradigm with transcranial Doppler ultrasound. RESULTS: There was no change in eupnic measures during or following the IH paradigm; however, the ventilatory response to IH increased by the last exposure (3.0±2.8 L·min(-1)). Cerebral blood flow velocity decreased and increased with hypocapnia and hypercapnia, respectively, but cerebrovascular sensitivity to CO2 remained unchanged with IH (PRE-IH: 2.58±0.50%/mmHg; POST-IH: 2.59±0.74%/mmHg). DISCUSSION: Our data indicates that 10 d of IH in healthy humans does not alter the cerebrovascular response to CO2. Redundancy of cerebrovascular regulation mechanisms to CO2 may work to counteract IH-induced dysregulation and protect cerebral tissue.

Dynamic cerebral autoregulation during and following acute hypoxia: role of carbon dioxide.

Previous research has shown an inconsistent effect of hypoxia on dynamic cerebral autoregulation (dCA), which may be explained by concurrent CO2 control. To test the hypothesis that hypoxic dCA is mediated by CO2, we assessed dCA (transcranial Doppler) during and following acute normobaric isocapnic and poikilocapnic hypoxic exposures. On 2 separate days, the squat-stand maneuver was used to determine dCA in healthy subjects (n = 8; 3 women) in isocapnic and poikilocapnic hypoxia exposures (end-tidal oxygen pressure 50 Torr for 20 min). In isocapnic hypoxia, the amplitude of the cerebral blood flow response to increases and decreases in mean arterial blood pressure were elevated (i.e., increases in gain of +35 and +28%, respectively; P < 0.05). However, dCA gain to increases in pressure was reduced compared with baseline (-32%, P < 0.05) following the isocapnic hypoxia exposure. Similarly, intravenous bolus injections of sodium nitroprusside and phenylephrine in a separate group of subjects (n = 8; 4 women) also demonstrated a reduction in dCA gain to hypertension following isocapnic hypoxia. In contrast, dCA gain with the squat-stand maneuver did not significantly change from baseline during or following poikilocapnic hypoxia (P > 0.05). Our results demonstrate that dCA impairment in isocapnic hypoxia can be prevented with hypocapnia, and highlight the integrated nature of hypoxic cerebrovascular control, which is under strong CO2 influence.

Repeated exercise-induced arterial hypoxemia in a healthy untrained woman.

A healthy 36-year-old untrained (maximal oxygen consumption (V(O2max)): 39 mL/kg/min) woman completed multiple graded exercise tests on a treadmill. Temperature-corrected arterial blood samples were obtained in addition to esophageal pressure. Significant hypoxemia (-13 mm Hg arterial oxygen tension decrease) and arterial oxyhemoglobin desaturation (-6% decrease) was observed relative to rest and occurred during submaximal exercise and worsened at maximal intensities. Expiratory flow limitation (28-40% intersection of tidal volume) was present at near-maximal intensities. Relieving mechanical ventilatory constraints with a helium inspirate (79% He:21% O(2)) partially reversed the hypoxemia. Conversely, increasing chemical ventilatory stimuli, with hypercapnia (3.5% CO(2)), failed to increase ventilation. Maintaining oxyhemoglobin saturation, via a mildly hyperoxic (26% O(2)) inspirate, increased exercise duration (+45 s) and V(O2max) (+5 mL/kg/min). We attribute the hypoxemia to an excessive A-a(O2) resulting from ventilation-perfusion mismatch and secondarily to mechanical ventilatory constraints. We conclude that a healthy untrained woman can develop EIAH and this remains stable over a period of 6 months.

Limitations of respiratory muscle and vastus lateralis blood flow during continuous exercise.

Measurement of regional blood flow to the respiratory muscles has traditionally been invasive. The blood flow index (BFI), a minimally invasive method using indocyanine green dye (ICG) and near infrared spectroscopy, allows assessment of within subject changes in regional blood flow. This study assessed regional BFI to the vastus lateralis muscle (QBFI) and the superficial respiratory muscles in the seventh intercostal space (RMBFI). Eight healthy subjects cycled continuously at incrementally more difficulty stages to exhaustion. In our subjects, QBFI declined between 83% and 100% of maximal exertion (p=0.002) and no statistically significant changes in RMBFI were seen despite steadily increasing ventilatory workloads. Post hoc pairwise comparisons demonstrated that QBFI at 83% work (0.015µmoless(-1)±0.005) was significantly higher than at maximum work output (0.011µmoless(-1)±0.004, p=0.007). There were no other significant differences of QBFI between maximum work output and different levels of work. The current study suggests that respiratory and locomotor muscle blood flow during sub-maximal and maximal exertion is unable to match increasing workloads.

Effects of 10 days of modest intermittent hypoxia on circulating measures of inflammation in healthy humans.

PURPOSE: Obstructive sleep apnea (OSA) is a common disease which is associated with elevated inflammatory markers and adhesion molecules, possibly due to nightly intermittent hypoxia (IH). The purpose of this study was to test the hypothesis that IH would increase systemic inflammatory markers in healthy human males. METHODS: Healthy, young male subjects (n = 9; 24 ± 2 years) were exposed to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation = 80%, 1 h/day) for 10 consecutive days. Serum granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1ß, interleukin-6, interleukin-8, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured before and following the 10 days of IH using Luminex. RESULTS: Nine subjects completed the study (24 ± 2 years; 24 ± 2 kg/m(2)). The mean oxyhemoglobin saturation was 80.8 ± 1.6% during the hypoxia exposures. There was no significant change in any of the markers of inflammation (paired t test, P > 0.2 all cytokines). CONCLUSIONS: These findings suggest that (1) a more substantial or a different pattern of hypoxemia might be necessary to activate systemic inflammation, (2) the system may need to be primed before hypoxic exposure, or (3) increases in inflammatory markers in patients with OSA may be more related to other factors such as obesity or nocturnal arousal.

Baroreflex control of muscle sympathetic nerve activity as a mechanism for persistent sympathoexcitation following acute hypoxia in humans.

This study tested the hypothesis that acute isocapnic hypoxia results in persistent resetting of the baroreflex to higher levels of muscle sympathetic nerve activity (MSNA), which outlasts the hypoxic stimulus. Cardiorespiratory measures were recorded in humans (26 ± 1 yr; n = 14; 3 women) during baseline, exposure to 20 min of isocapnic hypoxia, and for 5 min following termination of hypoxia. The spontaneous baroreflex threshold technique was used to determine the change in baroreflex function during and following 20 min of isocapnic hypoxia (oxyhemoglobin saturation = 80%). From the spontaneous baroreflex analysis, the linear regression between diastolic blood pressure (DBP) and sympathetic burst occurrence, the T50 (DBP with a 50% likelihood of a burst occurring), and DBP error signal (DBP minus the T50) provide indexes of baroreflex function. MSNA and DBP increased in hypoxia and remained elevated during posthypoxia relative to baseline (P < 0.05). The DBP error signal became progressively less negative (i.e., smaller difference between DBP and T50) in the hypoxia and posthypoxia periods (baseline: -3.9 ± 0.8 mmHg; hypoxia: -1.4 ± 0.6 mmHg; posthypoxia: 0.2 ± 0.6 mmHg; P < 0.05). Hypoxia caused no change in the slope of the baroreflex stimulus-response curve; however, there was a shift toward higher pressures that favored elevations in MSNA, which persisted posthypoxia. Our results indicate that there is a resetting of the baroreflex in hypoxia that outlasts the stimulus and provide further explanation for the complex control of MSNA following acute hypoxia.

Blood flow index using near-infrared spectroscopy and indocyanine green as a minimally invasive tool to assess respiratory muscle blood flow in humans.

Near-infrared spectroscopy (NIRS) in combination with indocyanine green (ICG) dye has recently been used to measure respiratory muscle blood flow (RMBF) in humans. This method is based on the Fick principle and is determined by measuring ICG in the respiratory muscles using transcutaneous NIRS in relation to the [ICG] in arterial blood as measured using photodensitometry. This method is invasive since it requires arterial cannulation, repeated blood withdrawals, and reinfusions. A less invasive alternative is to calculate a relative measure of blood flow known as the blood flow index (BFI), which is based solely on the NIRS ICG curve, thus negating the need for arterial cannulation. Accordingly, the purpose of this study was to determine whether BFI can be used to measure RMBF at rest and during voluntary isocapnic hyperpnea at 25, 40, 55, and 70% of maximal voluntary ventilation in seven healthy humans. BFI was calculated as the change in maximal [ICG] divided by the rise time of the NIRS-derived ICG curve. Intercostal and sternocleidomastoid muscle BFI were correlated with simultaneously measured work of breathing and electromyography (EMG) data from the same muscles. BFI showed strong relationships with the work of breathing and EMG for both respiratory muscles. The coefficients of determination (R(2)) comparing BFI vs. the work of breathing for the intercostal and sternocleidomastoid muscles were 0.887 (P < 0.001) and 0.863 (P < 0.001), respectively, whereas the R(2) for BFI vs. EMG for the intercostal and sternocleidomastoid muscles were 0.879 (P < 0.001) and 0.930 (P < 0.001), respectively. These data suggest that the BFI closely reflects RMBF in conscious humans across a wide range of ventilations and provides a less invasive and less technically demanding alternative to measuring RMBF.

Sex differences in exercise-induced diaphragmatic fatigue in endurance-trained athletes.

There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 +/- 1.9 ml x kg(-1) x min(-1)) and women (n = 19; maximal aerobic capacity = 57.1 +/- 1.5 ml x kg(-1) x min(-1)). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a >or=15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 +/- 2.3, 20.7 +/- 3.2, and 13.3 +/- 4.5%, respectively, whereas results in women (n = 8) were 21.0 +/- 2.1, 11.6 +/- 2.9, and 9.7 +/- 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts.

Hyperoxia attenuates muscle sympathetic nerve activity following isocapnic hypoxia in humans.

Hypoxia may sensitize the carotid chemoreceptors, resulting in a sustained elevation of muscle sympathetic nerve activity (MSNA) that outlasts the hypoxic stimulus. To test this hypothesis, we determined the effect of carotid body inhibition on the sustained elevation of MSNA following isocapnic hypoxia in humans. Seven healthy subjects (5 male, 2 female) breathed 100% O(2) (hyperoxia) for 1 min before (2 interventions) and after (2-3 interventions) 20 min of isocapnic hypoxia (80% arterial oxyhemoglobin saturation). MSNA was continuously recorded from the common peroneal nerve with microneurography. There was no effect of hyperoxia on MSNA before exposure to isocapnic hypoxia. During the isocapnic hypoxia exposure, there was an increase in minute ventilation and heart rate that subsided once hypoxia was terminated. In contrast, there was an increase in MSNA burst frequency that persisted for approximately 25 min after cessation of the stimulus. Hyperoxia resulted in a transient reduction in MSNA burst frequency of 28% (P < 0.05), 15% (P < 0.05), and 9% (P > 0.05) in the three posthypoxia interventions, respectively. Our results suggest that input from the carotid chemoreceptors is obligatory for the sustained elevation of MSNA initiated by chemoreflex stimulation. We attribute the decrease in MSNA to a transient hyperoxia-induced attenuation of carotid chemoreceptor sensitivity.

The pulmonary system during exercise in hypoxia and the cold.

The demands for pulmonary O(2) and CO(2) transport in the exercising human are substantial. Fortunately, the regulatory and architectural limits of the pulmonary system meet the requirements of heavy exercise in most individuals. However, in some highly trained athletes the high metabolic demand of intense exercise is in excess of the capacity of the pulmonary system. Environmental considerations, in addition to those imposed by the demands of exercise, provide further physiological challenges that must be met. Winter athletes often encounter high-altitude hypoxia and cold, either transiently during competition or repeatedly during training. In this brief review, we examine the pulmonary system during acute and chronic exercise in hypoxic and cold environmental conditions. Observations from studies conducted in humans are emphasized in order to ask questions about regulation, plasticity and the limits of human physiology. We also highlight new findings and controversial questions that would benefit from additional study.

Sex differences in the resistive and elastic work of breathing during exercise in endurance-trained athletes.

It is not known whether the high total work of breathing (WOB) in exercising women is higher due to differences in the resistive or elastic WOB. Accordingly, the purpose of this study was to determine which factors contribute to the higher total WOB during exercise in women. We performed a comprehensive analysis of previous data from 16 endurance-trained subjects (8 men and 8 women) that underwent a progressive cycle exercise test to exhaustion. Esophageal pressure, lung volumes, and ventilatory parameters were continuously monitored throughout exercise. Modified Campbell diagrams were used to partition the esophageal-pressure volume data into inspiratory and expiratory resistive and elastic components at 50, 75, 100 l/min and maximal ventilations and also at three standardized submaximal work rates (3.0, 3.5, and 4.0 W/kg). The total WOB was also compared between sexes at relative submaximal ventilations (25, 50, and 75% of maximal ventilation). The inspiratory resistive WOB at 50, 75, and 100 l/min was 67, 89, and 109% higher in women, respectively (P < 0.05). The expiratory resistive WOB was 131% higher in women at 75 l/min (P < 0.05) with no differences at 50 or 100 l/min. There were no significant sex differences in the inspiratory or expiratory elastic WOB across any absolute minute ventilation. However, the total WOB was 120, 60, 50, and 45% higher in men at 25, 50, 75, and 100% of maximal exercise ventilation, respectively (P < 0.05). This was due in large part to their much higher tidal volumes and thus higher inspiratory elastic WOB. When standardized for a given work rate to body mass ratio, the total WOB was significantly higher in women at 3.5 W/kg (239 +/- 31 vs. 173 +/- 12 J/min, P < 0.05) and 4 W/kg (387 +/- 53 vs. 243 +/- 36 J/min, P < 0.05), and this was due exclusively to a significantly higher inspiratory and expiratory resistive WOB rather than differences in the elastic WOB. The higher total WOB in women at absolute ventilations and for a given work rate to body mass ratio is due to a substantially higher resistive WOB, and this is likely due to smaller female airways relative to males and a breathing pattern that favors a higher breathing frequency.

Effects of intermittent hypoxia on the cerebrovascular responses to submaximal exercise in humans.

Intermittent hypoxia (IH) has been shown to alter the ventilatory and cardiovascular responses to submaximal exercise; however, the effect of IH on the cerebral blood flow (CBF) response to submaximal exercise has not been determined. This study tested the hypothesis that IH would blunt the CBF response during eucapnic and hypercapnic exercise. Nine healthy males underwent 10 consecutive days of isocapnic IH (oxyhaemoglobin saturation = 80%, 1 h day(-1)). Ventilatory, cardiovascular, and cerebrovascular responses to cycle exercise (50, 100, and 150 W) were measured before and after IH. Carbon dioxide (5% CO(2)), a mediator of CBF during exercise, was administered for 2 min of each exercise stage. Over the 10 days of IH, there was an increase in minute ventilation [Formula: see text] during the IH exposures (P < 0.05). Although exercise produced increases in [Formula: see text] middle cerebral artery mean velocity (MCA V (mean)), and mean arterial pressure (P < 0.05), there was no effect of IH. Similarly, hypercapnic exercise increased [Formula: see text] and MCA V (mean) (P < 0.05); however, the magnitude of the response was unchanged following IH. Our findings indicate that ten daily hypoxia exposures does not alter the CBF response to submaximal exercise.

Intermittent hypoxia reduces cerebrovascular sensitivity to isocapnic hypoxia in humans.

The purpose of this study was to determine the changes in human cerebrovascular function associated with intermittent poikilocapnic hypoxia (IH). Healthy men (n=8; 24+/-1 years) were exposed to IH for 10 days (12% O(2) for 5min followed by 5min of normoxia for 1h). During the hypoxic exposures, oxyhemoglobin saturation (SaO(2)) was 85% and the end-tidal partial pressure of CO(2) was permitted to fall as a result of hypoxic hyperventilation. Pre- and post-IH intervention subjects underwent a progressive isocapnic hypoxic test where ventilation, blood pressure, heart rate, and cerebral blood flow velocity (middle cerebral artery, transcranial Doppler) were measured to determine the ventilatory, cardiovascular and cerebrovascular sensitivities to isocapnic hypoxia. When compared to the pre-IH trial, cerebrovascular sensitivity to hypoxia significantly decreased (pre-IH=0.28+/-0.15; post-IH=0.16+/-0.14cms(-1)%SaO(2)(-1); P<0.05). No changes in ventilatory, blood pressure or heart rate sensitivity were observed (P>0.05). We have previously shown that the ability to oxygenate cerebral tissue measured using spatially resolved near infrared spectroscopy is significantly reduced following IH in healthy humans. Our collective findings indicate that intermittent hypoxia can blunt cerebrovascular regulation. Thus, it appears that intermittent hypoxia has direct cerebrovascular effects that can occur in the absence of changes to the ventilatory and neurovascular control systems.

Regulation of cerebral blood flow during exercise.

Constant cerebral blood flow (CBF) is vital to human survival. Originally thought to receive steady blood flow, the brain has shown to experience increases in blood flow during exercise. Although increases have not consistently been documented, the overwhelming evidence supporting an increase may be a result of an increase in brain metabolism. While an increase in metabolism may be the underlying causative factor for the increase in CBF during exercise, there are many modulating variables. Arterial blood gas tensions, most specifically the partial pressure of carbon dioxide, strongly regulate CBF by affecting cerebral vessel diameter through changes in pH, while carbon dioxide reactivity increases from rest to exercise. Muscle mechanoreceptors may contribute to the initial increase in CBF at the onset of exercise, after which exercise-induced hyperventilation tends to decrease flow by pial vessel vasoconstriction. Although elite athletes may benefit from hyperoxia during intense exercise, cerebral tissue is well protected during exercise, and cerebral oxygenation does not appear to pose a limiting factor to exercise performance. The role of arterial blood pressure is important to the increase in CBF during exercise; however, during times of acute hypotension such as during diastole at high-intensity exercise or post-exercise hypotension, cerebral autoregulation may be impaired. The impairment of an increase in cardiac output during exercise with a large muscle mass similarly impairs the increase in CBF velocity, suggesting that cardiac output may play a key role in the CBF response to exercise. Glucose uptake and CBF do not appear to be related; however, there is growing evidence to suggest that lactate is used as a substrate when glucose levels are low. Traditionally thought to have no influence, neural innervation appears to be a protective mechanism to large increases in cardiac output. Changes in middle cerebral arterial velocity are independent of changes in muscle sympathetic nerve activity, suggesting that sympathetic activity does not alter medium-sized arteries (middle cerebral artery).CBF does not remain steady, as seen by apparent increases during exercise, which is accomplished by a multi-factorial system, operating in a way that does not pose any clear danger to cerebral tissue during exercise under normal circumstances.