Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects

Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.     

Comparison of respiratory and circulatory human responses to progressive hypoxia and hypercapnia.

The effects of acute, progressive isocapnic hypoxia and hyperoxic hypercapnia on lung ventilation, heart rate, cardiac output and arterial blood pressure were determined simultaneously in 32 normal individuals. All subjects were exposed to hypoxia and hypercapnia in an entire range of individual tolerance. The piecewise linear approximation technique was used for analysis of the ventilatory and circulatory response curves. In all subjects, the changes in hemodynamics in the response to hypoxia paralleled those occurring in ventilation, during both the first phase of slow increase and the second phase of sharp increase. Fracture point coordinates for ventilation and circulation coincided, with the fracture being registered at an end-tidal PO2 of 79.7 +/- 3.8 mm Hg for ventilation and 79.0 +/- 4.5 mm Hg (p greater than 0.1) for cardiac output. This may give evidence of analogous entries from the peripheral O2-sensitive receptors to the respiratory and vascular motor bulbar centers. By contrast, a more significant rise in ventilation observed during the hypercapnic versus hypoxic drive was not accompanied by any change in the heart rate, cardiac output and arterial blood pressure until the end-tidal PCO2 (PETCO2) had reached a critical level. Fracture point coordinates for ventilation and circulation did not coincide, with the fracture being registered at a PETCO2 of 51.1 +/- 1.9 mm Hg for the former and 57.0 +/- 2.2 mm Hg (p less than 0.01) for the latter. Such differences in the response to hypoxia and hypercapnia were repeatedly observed during 5 test days. The data do not seem to show evidence in favor of an involvement of the hypercapnic challenge in the central regulation of the circulation.     

Laryngeal muscle activities during progressive hypercapnia and hypoxia in awake and sleeping dogs

Laryngeal, intercostal and diaphragmatic muscle activities were recorded during progressive hypercapnia and hypoxia in dogs with chronically implanted electrodes. As ventilation increased during progressive chemoreceptor stimulation, inspiratory activity of the posterior cricoarytenoid muscle, a laryngeal abductor, and of the cricothyroid muscle were augmented. When expiratory flow rates reached 2-3 times resting levels, both of these muscles were also active during expiration and recruitment of the internal intercostal muscles was observed. The thyroarytenoid muscle, a laryngeal adductor, was active only rarely and no consistent activation of this muscle was observed with either hypercapnia or hypoxia. The patterns of muscle activation in response to respiratory stimulation were not different during wakefulness, slow wave sleep, and rapid eye movement sleep. The results indicate that the laryngeal muscles are activated during hypercapnia and hypoxia in a manner which reduces both inspiratory and expiratory airflow resistance regardless of sleep-wakefulness state.     

Ventilation and breathing pattern during progressive hypercapnia and hypoxia after human heart-lung transplantation

The effects of human pulmonary denervation on the ventilatory responses to progressive hyperoxic hypercapnia and isocapnic hypoxia as well as the effect on resting breathing pattern were evaluated in nine female heart-lung transplant (H-LT) recipients. The results were compared to those obtained from 10 normal women of comparable age and stature. Testing was performed 2 to 37 months after H-LT (median, 7.5 months). Cardiac function was normal in all H-LT recipients. None of the patients had spirometric evidence of airway obstruction, while six had a restrictive pattern with forced vital capacities less than 80% of predicted values. Resting minute ventilation (VE), tidal volume (VT), and ventilatory drive (VT/TI) in the H-LT recipients were not significantly different from those of the normal subjects. Inspiratory time (TI), however, was significantly shorter in the H-LT patients (1.64 +/- 0.2 versus 2.09 +/- 0.13 s, p = 0.035), and resting breathing frequency (F) tended to be greater in the H-LT recipients (16.27 +/- 2.04 versus 12.82 +/- 0.53 breaths/min, p = 0.052). The overall ventilatory response to hypercapnia was reduced after H-LT (0.91 +/- 0.17 versus 1.5 +/- 0.27 L/min/mm Hg CO2, p less than 0.043), as was the F response (0.2 +/- 0.09 versus 0.65 +/- 0.13 breaths/min/mm Hg CO2, p less than 0.01). The VT and VT/TI responses to hypercapnia did not differ between the H-LT recipients and normal subjects. There were no significant differences between the two groups with respect to the responses to progressive hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of hypercapnia and hypoxia on single hypoglossal nerve fiber activity

The respiratory related modulation of hypoglossal nerve activity has been studied at the single fiber level in cats under hyperoxic hypercapnia and hypoxic conditions and their conduction velocities determined. Changes in fiber activity were compared to simultaneous changes occurring in phrenic activity. Three different kinds of discharge patterns were observed: (a) inspiratory, (b) phasic activity during both inspiration and expiration, and (c) continuous random activity with no respiratory modulation. These fibers could be grouped into three categories according to their pattern of discharge during CO2 breathing. Type I fibers, mean conduction velocity of 30.0 m/sec, exhibited only an inspiratory phasic discharge during 100% O2 breathing. Their discharge frequency increased rapidly with higher levels of CO2 and hypoxia. Type II fibers, mean conduction velocity of 36.7 m/sec, had three different kinds of inspiratory-expiratory discharge patterns during 100% O2 breathing. With increasing hypercapnia or hypoxia fibers of this group discharged phasically during inspiration and discharge at low frequency during expiration. Type III fibers had a non phasic discharge pattern at 100% O2 breathing and at all levels of CO2 tested (up to 10%). Discharge frequency rose during CO2 rebreathing and hypoxia, but the rate of increase was much less than Type I and Type II fibers. Their mean conduction velocity was 41.3 m/sec. The inspiratory activity of Type I and II fibers increased their activity more than the phrenic during hypercapnia and hypoxia. Type II and Type III fibers are responsible at least in part for the tonic activity of the nerve.     

Aging effects on the interaction of hypercapnia and hypoxia as ventilatory stimuli

We measured ventilatory responses to progressive hypercapnia at two steady-state levels of oxygenation and to progressive hypoxia at two steady-state levels of CO2 in 10 elderly and 10 young individuals. Under hyperoxic conditions, the ventilatory response to progressive hypercapnia was not significantly different between age groups but, under hypoxic conditions, the response to hypercapnia was lower in the elderly group. The interaction of hypercapnic and hypoxic stimuli was greater among young persons as indicated by a higher ratio of the hypercapnic response slopes (hypoxic/hyperoxic); 1.48 +/- 0.19 versus 0.98 +/- 0.11, p less than .05. The ventilatory response to hypoxia at the lower CO2 level was significantly greater among elderly than among young adults but not significantly different between age groups at the higher CO2 level. The ratio of hypoxic response slopes (high PCO2/lower PCO2) was 1.56 +/- 0.17 among elderly participants and 3.14 +/- 0.63 among young participants (p less than .05). These results suggest that aging diminishes the multiplicative effect of hypercapnia and hypoxia as ventilatory stimuli.     

Acute effects of hypercapnia and hypoxia on minute ventilation in unrestrained Weddell seals

We studied the ventilatory response to hypoxia and hypercapnia in five freely diving juvenile Weddell seals (age = 2 years) at McMurdo Station, Antarctica. The ventilatory response to CO2 was brisk, with minute ventilation increasing as a linear function of end tidal CO2 with an average slope of 3.1 L X (min X mm Hg)-1. The ventilatory response to hypoxia was small and variable. End tidal PO2 values as low as 28 mm Hg provoked at most a doubling of minute ventilation. These results were supported by the observation that elevated end tidal CO2 always inhibited voluntary diving whereas low PO2 values did not. Comparison of the Weddell seals' CO2 responsiveness to that of other mammals reveals similar CO2 sensitivity. We conclude that CO2 is the major determinant of ventilatory drive in wild Weddell seals.     

Differential effects of hypoxia and hypercapnia on respiratory sinus arrhythmia in conscious dogs

To test the hypothesis that hypoxia and hypercapnia have different effects on the genesis of respiratory sinus arrhythmia (RSA), the magnitude of RSA to these stimuli was compared in 3 unanesthetized dogs. Respiration was continuously monitored through a permanent tracheostomy, and the electrocardiogram and blood pressure were also monitored. The magnitude of RSA was assessed as an instantaneous amplitude of the R-R interval oscillation in the high-frequency band of 0.15-0.80Hz by means of complex demodulation. In a total of 47 runs with hypoxia, heart rate, mean arterial pressure, respiratory rate and tidal volume increased, but RSA magnitude decreased even after adjusting for the effects of respiratory rate and tidal volume. In a total of 39 runs with hypercapnia, heart rate and mean arterial pressure did not change, despite the increased respiratory rate and tidal volume. In contrast to hypoxia, RSA magnitude increased even after adjusting for the effects of respiratory rate and tidal volume. The different effects of the two respiratory stimuli on RSA magnitude were noted at any level of ventilation and support the original hypothesis.     

Ventilatory responses to hypercapnia and hypoxia following chronic hypercapnia in the rat

This study investigated the effects of an 18 week exposure to 10% CO(2) in air on minute ventilation (V(E)), breathing pattern and the chemoresponiveness of rats to hypoxic and hyperoxic stimuli. We found that V(E) remained elevated over the 18 weeks. Nonetheless, the breathing pattern changed significantly. Tidal volume increased and the durations of inspiration and the total cycle decreased. After the sustained hypercapnia the mean Pa(CO(2)) was 72.0+/-5.1 (S. D.) mmHg. Every 6 weeks the chemoresponiveness of the CO(2)-exposed rats was tested by an acute exposure sequentially to room air, then a 6% O(2), 10% CO(2) and 84% N(2) gas mixture, and finally a 90% O(2) in 10% CO(2) mixture. On either room air or the hyperoxic-hypercapnic mixture V(E) fell to its pre-hypercapnic level. On the hypoxic-hypercapnic mixture V(E) increased significantly. These results demonstrate that the initial stimulating effect of 10% CO(2) on V(E) persisted for the entire 18 weeks without altering hypoxic or hyperoxic ventilatory responses.     

The effects of catecholamines on ventilation in rainbow trout during hypoxia or hypercapnia

This study assessed the effects of experimentally elevated plasma catecholamine levels on gill ventilation in rainbow trout (Oncorhyncus mykiss) exposed to various external ventilatory stimulants. Trout were exposed to hypoxia (water PO2 (PwO2) = 90 Torr) or hypercapnia (water PCO2 (PwCO2) = 4.5 Torr) for 30 min. These conditions caused gill ventilation volume (Vw) to increase by 2.3- and 1.5-fold, respectively, but did not stimulate release of catecholamines into the blood. While the stimulus (hypoxia or hypercapnia) was maintained, fish were given a bolus injection (0.3 ml), followed by intra-arterial infusion (0.6 ml.h-1), of a catecholamine mixture (2 x 10(-5) mol.l-1 adrenaline + 5 x 10(-6) mol.l-1 noradrenaline) to mimic the physiological concentrations and ratios of these catecholamines observed under more severe hypoxic or hypercapnic conditions. In hypoxic fish, this treatment caused a significant, but transient (5 min) depression of ventilation while during hypercapnia, the administration of exogenous catecholamines caused a more prolonged hypoventilatory response. These hypoventilatory responses occurred despite a catecholamine-induced blood acidosis (a potential ventilatory stimulant). To assess the importance of initial Vw and/or blood respiratory status on catecholamine-mediated hypoventilation, these experiments were repeated under hyperoxic (PwO2 = 640 Torr) hyperoxic hypercapnic (PwO2 = 510 Torr, PwCO2 = 4.8 Torr) or normoxic (PwO2 = 151 Torr) conditions in which Vw was either depressed (3.9-fold during hyperoxia) or unaffected. Intra-arterial infusion of catecholamines did not affect Vw under either of these experimental conditions. These results demonstrate that during a respiratory challenge, such as hypoxia or hypercapnia, physiologically relevant levels of circulating catecholamines can depress Vw and therefore do not support a stimulatory role for circulating catecholamines in the control of ventilation in fish.     

Yoga and chemoreflex response to hypoxia and hypercapnia

We tested whether chemoreflex sensitivity could be affected by the practice of yoga, and whether this is specifically because of a slow breathing rate obtained during yoga or as a general consequence of yoga. We found that slow breathing rate per se substantially reduced chemoreflex sensitivity, but long-term yoga practice was responsible for a generalised reduction in chemoreflex.     

Renal compensation of hypercapnia in prolonged hypoxia

We previously showed that rats made hypoxic for three weeks were able to regulate their plasma pH better than normoxic rats during acute hypercapnia. This improved pH regulation was abolished by nephrectomy, suggesting that it was due, at least in part, to a more effective renal compensation of hypercapnia in hypoxic rats. To test this possibility renal acid excretion was measured in conscious rats that had been kept at PB 370-380 Torr for three weeks. The rats were studied in a chamber where PIO2 was kept at 68-70 Torr at ambient PB (740-750 Torr). Controls were pair-fed normoxic rats. After a 2 h control period, inspired PCO2 was increased for 4 h. The apparent non-bicarbonate buffer value of arterial blood plasma was twice as high in the hypoxic than in the normoxic rats. Renal excretion of ammonium increased to a similar extent during hypercapnia in both normoxic and hypoxic rats. Titratable acid excretion of normoxic rats did not change significantly during hypercapnia. In the hypoxic rats, on the other hand, total excretion of titratable acid in the 2 h control period was 90.9 +/- 16.4 mumol/rat; and increased to 150.0 +/- 13.4 mumol/rat in the first 2 h and to 232.9 +/- 26.0 mumol/rat in the last 2 h of hypercapnia. In spite of this large increase in acid excretion, urine pH of hypoxic rats did not change significantly, indicating a higher buffer value of the urine of hypoxic rats. These results confirm our previous observations and support the idea that the improved pH regulation of hypoxic rats is due in part to a more effective renal compensation of hypercapnia.     

Amiloride and carotid body chemoreception of hypercapnia and hypoxia

The sodium-proton (Na(+)-H+) antiporter has been found in virtually every tissue where its presence has been investigated. Its principal physiological role is to regulate intracellular pH (pHi). Amiloride (10(-3)-10(-4) M) is a known blocker of the antiporter when Na is present in normal physiological concentrations (130-140 x 10(-3) M). In order to determine if the Na(+)-H+ antiporter participated in the chemoreception of hypercapnia or hypoxia anesthetized, paralyzed, artificially ventilated cats were fitted with a loop in the right common carotid artery for the selective perfusion of the carotid body. Neural activity (imp/10 sec) was recorded from single or few fiber preparations during hypercapnia (PaCO2 = 48-64 Torr) while the carotid body was perfused with Krebs-Ringer bicarbonate solution for 2.5 min, then with its own hypercapnic arterial blood (4 min), then with Krebs-Ringer bicarbonate solution containing 0.6-0.8 x 10(-3) M amiloride (2.5 min), then with its own hypercapnic blood (4 min). After 20 min of rest the protocol was repeated during hypoxia (PaO2 = 35-45 Torr). The carotid body response to hypercapnic blood was unaffected by a preceding perfusion of the amiloride-containing solution but the response to hypoxic blood was decreased by 25% by the amiloride-containing solution. The data suggest the possibility of different mechanisms being involved in the chemoreception of hypercapnia and hypoxia.     

Chronotropic incompetence: a common and progressive finding in pacemaker patients.

Thirty-eight patients (ages 40 to 77 years, mean 63) followed in a pacemaker clinic underwent exercise treadmill tests to determine chronotropic incompetence. There were 28 men and 10 women. Twenty-seven patients had atrioventricular (AV) block and 11 patients had sick sinus syndrome. All patients were exercised to fatigue. None of the patients were receiving beta-blockers or other drugs that could reduce heart rate. Maximum heart rate (MHR) and percent predicted maximum heart rate (% PMHR) were used as an index of chronotropic incompetence. Chronotropic incompetence was defined as inability to achieve a % PMHR of greater than 80%. The overall incidence of chronotropic incompetence was 58% (22 of 38 patients). We examined the relationship between chronotropic incompetence and the time to pacemaker implantation. We found that in patients who had pacemakers for less than 2 years, the mean MHR was 125 +/- 21.6 beats/min compared with 111.9 +/- 23.6 beats/min for patients who had pacemakers implanted for longer than 4 years. Similarly, the mean % PMHR decreased from 76.5 +/- 12.5% to 68.7 +/- 15.4% in patients with pacemakers less than 2 years versus those with pacemakers for more than 4 years. Fifty-three percent of the patients with a pacemaker less than 2 years old were chronotropic incompetent versus 70% of the patients with a pacemaker more than 4 years old. These data suggest that chronotropic incompetence worsens with time after pacemaker implant. To further support this, eight patients with AV block underwent a second stress test an average of 2 years following the first.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac responses to hypoxia and hypercapnia in spinal man

The purpose of this study was to evaluate the effect of interruptionof the descending supraspinal sympathetic outflow on heart ratecontrol during exposures to chemical stimuli. We investigatedthe heart rate responses to progressive isocapnic hypoxia andhyperoxic hypercapnia using the rebreathing technique and quantifiedthe relationship between heart rate (HR), oxygen saturation(SaO₂), alveolar PCO₂ (P_ACO₂), and minute ventilation (V_E) in16 chronic tetraplegic subjects with low cervical spinal cordtransection. The HR responses were determined from the linearslopes of HR on SaO₂ and HR on P_ACO₂. We found that mean restingheart rate was within normal range; 66 ±3 (SEM) beatsmin^–1. HR increased as oxygenation fell or CO₂ tensionrose. The mean tetraplegic HR/SaO₂ was 0.83 ± 0.14 beatsmin^–1 per 1% fall in SaO₂ and that of HR/P_ACO₂ was 0.30± 0.13 beats min^–1 per mmHG rise in P_ACO₂. TheHR and V_E responses to either hypoxia or hypercapnia were relatedin the tetraplegic subjects. We conclude that the stimulatoryHR reponses to chemical stimuli are not suppressed by cervicalspinal cord transection. Thus, the descending sympathetic activitydoes not underlie the HR acceleration by chemical stimuli.     

Genioglossal recruitment during acute hypoxia and hypercapnia in kittens

We examined genioglossal and diaphragmatic EMG activities in one- and two-month-old anesthetized kittens during acute exposures to hypoxic (13% or 10% O2) and hyperoxic hypercapnic (8% CO2/50% O2/balanced N2) gas mixtures. Phasic genioglossal EMG activity, frequently characterized by a combined inspiratory-expiratory discharge pattern, was observed in 3 of 8 one-month-old vs. 7 of 7 two-month-old kittens during hypercapnia (Chi-square P less than 0.05). The percentage of kittens recruiting genioglossal activity during hypoxic exposures was similar at both ages (1 month, 75%; 2 month, 83%). Analysis of the breath-by-breath response during trials of hypoxia in which genioglossal recruitment was observed, however, revealed that the one-month-old kittens exhibited phasic genioglossal activity in only 40 +/- 27% of the stimulated breaths, compared to 63 +/- 26% for the two-month-old ones (P less than 0.05) at each level of hypoxia. In this regard, the genioglossal response to hypoxia in one-month-old kittens was frequently characterized by early and only transient recruitment (when diaphragmatic activity was at its peak), while genioglossal recruitment was more sustained in two-month-old animals. These data indicate that genioglossal activity in kittens is often recruited during exposures to hypercapnia and hypoxia, and suggest that such recruitment is more frequent with increasing postnatal age.