Effects of hypercapnia and hypoxia on laryngeal resistance to airflow.

Ventilation, laryngeal resistance and electromyograms of the diaphragm, posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were recorded in anesthetized, spontaneously breathing cats during 100% O2 administration and during steady state inhalation of hypercapnic and hypoxic gas mixtures. As shown previously, hyperoxic hypercapnia lowered expiratory laryngeal resistance (RlarE). Isocapnic hypoxia also lowered RlarE, and hypercapnia superimposed on hypoxia decreased it further. Hypocapnia raised RlarE. Changes in inspiratory laryngeal resistance (RlarI) were similar to those in RlarE, but smaller. When ventilation was stimulated to the same extent by hypoxia and by hypercapnia, RlarE was lower under hypoxic than hypercapnic conditions in most animals. The electromyograms showed that the respiratory oscillations in laryngeal resistance and the laryngeal responses to hypercapnia and hypoxia were determined chiefly by the activity of the PCA muscle, the abductor of the vocal cords. The TA-a representative adductor muscle-was silent under all conditions studied. The results, considered with previous work, indicate that the larynx plays a part in determining the breathing pattern under resting conditions and during respiratory stimulation by hypercapnia and hypoxia.     

Hypercapnic acidosis and compensated hypercapnia in control and pulmonary hypertensive piglets

Low tidal volume/inspiratory pressure ventilator strategies result in hypercapnia, which has been shown to increase pulmonary vasomotor tone. This may be particularly detrimental in infants and children with preexistent pulmonary hypertension. In this study, a piglet model of chronic hypoxia-induced pulmonary hypertension was used to test the hypotheses that: 1) the effects of hypercapnic acidosis are exaggerated by preexistent pulmonary hypertension; and 2) the pulmonary hemodynamic effects of hypercapnic acidosis are attenuated by normalizing pH. Pulmonary hypertension was induced by 2 weeks of hypoxia. Hemodynamic responses were measured in control and pulmonary hypertensive piglets during both normoxia and hypoxia under normocapnic, hypercapnic acidotic, and compensated hypercapnic conditions. We found that: 1) hypercapnic acidosis increased both normoxic and hypoxic pulmonary vascular resistance index (PVRI) in control piglets; 2) the pressor effects of hypercapnia were not attenuated by infusing bicarbonate to normalize the pH; and 3) piglets with chronic hypoxia-induced pulmonary hypertension had elevated baseline normoxic and hypoxic PVRI, but responded to hypercapnic acidosis and compensated hypercapnia in a similar way to control piglets. These data suggest that acute hypercapnic acidosis may have deleterious effects on the pulmonary hemodynamics of normal and pulmonary hypertensive subjects which may not be acutely reversed by buffering the pH.     

The progressive effects of ageing on chemosensitivity in healthy subjects

The aim of this study was to compare the central inspiratory drive (P(0.1)) response to hypoxia and hypercapnia between different age groups of elderly, nonsmoker, healthy subjects and young healthy controls. A random sample, proportionally stratified by age (65-69, 70-74, 75-79 and 80-84 yrs) from a sample of nonsmoker elderly subjects representative of a general population and 47 healthy subjects aged 20-40 were selected. Arterial blood gas, lung volumes, diffusing capacity, maximal respiratory pressure and oxygen uptake measurements were performed. Breathing pattern and mouth occlusion pressure, as well as P(0.1) responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia were evaluated. The elderly subjects had lower P0.1 responses to hypoxia (0.017+/-0.006 vs. 0.031+/-0.008 kPa/%, P<0.001) and hypercapnia (0.042+/-0.018 vs. 0.051+/-0.030 kPa/mmHg, P=0.047) than the young healthy controls. Hypoxic sensitivity gradually decreased as age increased to 70-74 and remained unchanged from 75 years of age onward. CO(2) threshold was lower in the elderly groups than in young healthy controls. Lung volumes, inspiratory muscle strength and baseline metabolic rate were the principal determinants of hypoxic sensitivity. In summary, during old age, a progressive decline in hypoxic sensitivity and a decrease in the CO(2) threshold are experienced. These alterations remain stable from the age of 75 onward.     

Influence of progressive and of transient hypoxia on upper airway resistance in normal humans

In order to evaluate the influence of hypoxia on upper airway patency, we measured the response of upper airway resistance (UAR) to progressive (P) normocapnic hypoxia (Rebuck's method) and transient (T) hypoxia (three to five breaths to 100% N2) in 11 normal men. Breath-by-breath inspiratory UAR was calculated at isoflow during exclusive nasal breathing. The UAR response to hypoxia was characterized by the changes in nasal resistance and pharyngeal resistance (PR) as a function of SaO2, mean inspiratory flow (VT/Tl), and changes in the end-expiratory lung volume (EELV) measured with an inductance vest. The ventilatory response to hypoxia was greater during T (-0.31 +/- 0.03 L/min/%SaO2; mean +/- SEM) than during P (-0.27 +/- 0.03 L/min/%SaO2, p = 0.05). UAR decreased as SaO2 decreased; this decrease was steeper during T than during P hypoxia (delta PR/%SaO2: 3.9 +/- 0.5 during P and 2.5 +/- 0.2 during T, p = 0.05). For the whole group, there was no difference in the slope of the decrease in UAR with increasing VT/Tl between the two hypoxic tests (delta PR/delta VT/Tl: -0.85 +/- 0.1 during P and -0.70 +/- 0.1 during T, p greater than 0.05). However, in four subjects, the slope of the relationship PR/VT/Tl during T remained steeper than during P. EELV increased as SaO2 decreased, with a greater increase during progressive than during transient hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Mechanical properties of the rabbit upper airway during hypoxia and hypercapnia

It has been suggested that the response of upper airway muscles to hypoxia may be different from the response of these muscles to hypercapnia. We therefore measured pulmonary ventilation and the mechanical properties of the isolated upper airway in 9 anesthetised rabbits during respiration of hypoxic and hypercapnic gas mixtures. Each animal was exposed to several levels of elevated inspiratory CO2 fraction, FICO2 (0.03 to 0.17) and depressed inspiratory O2 fraction, FIO2 (0.19 to 0.09). The steady-state ventilatory response, the tidal pressure in the upper airway (PTUA) and the upper airway elastance were measured under each condition. Straight lines were calculated by least squares regression relating pulmonary VT to FICO2 and FIO2 and PTUA to FICO2 and FIO2. The PTUA was estimated graphically at two levels of hypoxia and hypercapnia producing equal augmentation of VT. The ratio of PTUA during hypoxia to PTUA during hypercapnia was 1.06 +/- 0.21 (mean +/- 95% C.I.) at low VT and 1.15 +/- 0.25 at high VT. Elastance of the upper airway rose from 6.25 +/- 1.13 cmH2O/ml under control conditions to a maximum of 7.95 +/- 1.24 cmH2O/ml (P less than 0.05) during hypercapnia and to a maximum of 8.02 +/- 1.17 cmH2O/ml (P less than 0.05) during hypoxia. There was no difference between the mean (+/- 95% C.I.) change associated with hypercapnia (1.64 +/- 1.08 cmH2O/ml) and the mean change associated with hypoxia (1.77 +/- 1.26 cmH2O/ml). We concluded that hypoxia did not result in a greater change in upper airway mechanical properties than hypercapnia.     

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.     

Effect of inspiratory resistance of occlusion pressure in hypoxia and hypercapnia.

The authors measured ventilation and the mouth pressure developed during the first 0.1 sec of inspiratory effort against a closed airway (P 0.1) in response to normoxic hypercapnia and normocapnic hypoxia, with and without added inspiratory resistance. Hypercapneic responses were elicited by a steady-state technique, hypoxic responses by a non-steady-state technique. External resistance depressed the ventilatory response to CO2 but in general augmented the P 0.1 response. The degree of change of response was not predictable on the basis of the response in the absence of resistance. Hypoxic ventilatory response was also diminished by resistance and P 0.1 increased. The authors concluded that in normal subjects added inspiratory resistance increased inspiratory drive as assessed by P 0.1.     

Influence of phasic volume feedback on abdominal expiratory nerve activity

Our purpose was to examine the influence of phasic lung volume feedback on the activities of motor nerves innervating the diaphragm and transversus abdominis muscles during hypercapnia and hypoxia. We studied seventeen decerebrate cats that were paralyzed and ventilated with a servo-respirator controlled by the integrated phrenic neurogram. The effects of phasic lung volume feedback were assessed by withholding pulmonary inflation during the central inspiratory period. Withholding lung inflation for a single respiratory cycle under hyperoxic, normocapnic conditions consistently prolonged the durations of the inspiratory and expiratory periods, and caused marked increases in the peak electrical activities of both phrenic and abdominal nerves. Hyperoxic hypercapnia (PaCO2 50-80 mmHg) and isocapnic hypoxia (PaO2 60-35 mmHg) increased peak phrenic and abdominal neural activities, and withholding pulmonary inflation under these conditions caused even greater augmentations of inspiratory and expiratory motor output. The augmentation of expiratory activity by withholding lung inflation was proportionately greater than the concomitant prolongation of the central expiratory period. All responses to non-inflation maneuvers were abolished following bilateral cervical vagotomy. The results indicate that vagally mediated volume feedback during inspiration can attenuate the output of abdominal motoneurons in the subsequent expiratory period. Moreover, hypoxia, which attenuates abdominal motor activity in vagotomized animals, enhances this activity when the vagi are intact.     

Effect of Bedtime Ethanol on Total Inspiratory Resistance and Respiratory Drive in Normal Nonsnoring Men

We have previously reported that bedtime ethanol (2.0 ml/kg of 100 proof vodka) increases upper airway closing pressure in males who habitually snored but were otherwise healthy. We also observed that some of these snorers developed obstructive apneas. To explore this phenomenon in more detail, we measured the inspiratory resistance (R_I) and respiratory drive after bedtime ethanol in 10 nonobese men (ages 23 to 33) with no history of snoring. Subjects went to bed wearing a tightly fitting valved mask over the nose and mouth that allowed measurement of inspiratory and expiratory flow, pressure in the mask, and endtidal CO₂. We measured R_I by calculating the pressure difference between the mouth and a balloon positioned in the midesophagus. Respiratory drive was quantified by the inspiratory occlusion pressure (P_0.1), the ventilatory response to hyperoxic hypercapnia (ΔV_E/ΔP_ETCO₂), and the ventilatory response to isocapnic hypoxia (ΔV_E/ΔS,O₂). Measurements were made during waking and during stage 2 NREM sleep on two nights: (1) when the subjects drank 1.5 ml/kg of 100 proof vodka in orange juice over a 30-min period 15–45 min before lights out and (2) when the orange juice contained less than 0.1 ml of vodka floating on the top. Eight of the nine men in whom we had technically adequate measurements showed a rise in R_I during NREM sleep above the waking level on both control and ethanol nights and the sleeping R_I was greater on the ethanol than on the control night. There was a tendency for P_0.1 to be higher during sleep and greater on the ethanol night, suggesting that the neural output to the respiratory muscles was not depressed and may have been stimulated by the inspiratory “loading” secondary to the increased R_I. The hypercapnic response was significantly depressed during sleep. Whereas the response tended to be less on the ethanol than on the control night, the difference was not significant. The hypoxic response showed little change from waking to sleeping and no significant change with ethanol. We speculate that inspiratory loading due to increased upper airway resistance tends to stimulate respiratory drive and thereby partially offsets the depressant effect of ethanol on the central respiratory chemoreceptors.     

Peripheral chemosensitivity assessed by the modified transient O2 test in female twins

To evaluate genetic influence on the control of breathing in adult women, we measured, in healthy female twins, ventilatory responses to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia, and the withdrawal response (the modified transient O2 test) which is considered to selectively reflect peripheral chemoreceptor activity. The withdrawal response was obtained as the magnitude of initial depression in ventilation induced by two breaths of O2 from steady-state hypercapnic hypoxia. Nine monozygotic twin pairs, aged 44 +/- SD17 years, and 7 dizygotic twin pairs, aged 39 +/- 8 years, were studied. Mean values for ventilatory responses to hypoxia and hypercapnia, and the withdrawal response were not different between MZ and DZ. The within-pair variance ratio (VDZ/VMZ) for the withdrawal response was significantly greater than one (p less than 0.05), although neither VDZ/VMZ for the hypoxic response nor that for the hypercapnic response was greater than one. These observations suggest that the peripheral chemosensitivity is influenced by genetic factors even in adult women, including aged subjects, when genetic influence is not apparent in the ventilatory responses to progressive hypoxia and hypercapnia.     

Depression of hypoxic and hypercapnic ventilatory drives in severe asthma.

Because of the previous finding of an attenuated hypoxic ventilatory drive in a teenager with severe asthma, the ventilatory responses to hypoxia and hypercapnia were examined during remission in 16 patients with the history of severe asthma. Spirometric and body plethysmographic pulmonary functions were normal or nearly normal just prior to ventilatory drive testing. The ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia were studied. Both hypoxic and hypercapnic drives were significantly depressed in the asthmatic patients. Factors known to blunt the ventilatory drives were not present in this group of patients. Hence, the etiology of these changes is unclear. In some patients, these depressed respiratory drives might contribute to hypoventilation, to severe hypoxemia, and to respiratory failure during severe asthma.     

Differential effects of CO2 and hypoxia on bronchomotor tone in the newborn dog

We compared the effects of hypoxia and hypercapnia on pulmonary mechanics in the newborn dog. Animals were anesthetized with a mixture of chloralose/urethane, paralyzed and ventilated with the chest open. Following an inflation to control volume history, mean inspiratory resistance (RLi) and dynamic compliance (CLdyn) were measured on a breath-by-breath basis during ventilation with control (FIO2 = 0.4), hypoxic (FIO2 = 0.1) and hypercapnic (FICO2 = 0.05) gas mixtures. Hypercapnia increased RLi 63% (n = 9) while hypoxia increased RLi in only 1/9 animals. Neither gas mixture changed CLdyn compared to control. The response to hypercapnia and the lone hypoxic response were eliminated by denervation of the airways by atropine administration or vagotomy. Following airway denervation hypoxia caused a small but statistically significant fall in CLdyn compared to the denervated control. These findings demonstrate that the newborn dog is capable of reflexly increasing bronchomotor tone and that vagal efferent innervation to the airways is functional at birth. Our data also suggest that in the newborn, central chemoreceptors are more effective than peripheral chemoreceptors in altering vagal tone to airway smooth muscle. Increased bronchomotor tone with hypercapnia may help to prevent dynamic compression of the airways.     

Chronotropic effects of progressive hypoxia and hypercapnia

The effects of acute, progressive isocapnic hypoxia and hyperoxic hypercapnia on heart rate (HR) were determined in 13 normal individuals. In all subjects there was an inverse linear relationship between hemoglobin oxygen saturation and HR. For the group, the HR (mean +/- SE) increased from 72 +/- 2 to 89.5 +/- 3 beats/min representing a 25% increase. During progressive hypercapnia, the HR increased from 72 +/- 2 to 75 +/- 2 beats/min, representing only a 4% increase. In contrast to the HR response to hypoxia, there was a heterogeneous HR response to hypercapnia, with most subjects having a mild increase in HR, but some showing no response and a few exhibiting a decrease in HR. We conclude that although there is a significant tachycardic response to isocapnic hypoxia, the tachycardic response to hyperoxic hypercapnia is small and clinically insignificant. In addition, while there is uniformly a tachycardic response to isocapnic hypoxia, there is a considerable interindividual variability of the HR response to hyperoxic hypercapnia.     

Role of diffuse airway obstruction in the hypercapnia of obstructive sleep apnea

The mechanisms responsible for the development of chronic hypercapnia in patients with obstructive sleep apnea (OSA) are not well defined. Therefore, we tested the hypothesis that diffuse airway obstruction may be involved by studying 50 patients with a well-documented OSA syndrome. Seven patients had daytime hypercapnia with a mean PaCO2 of 51 +/- 2 (SEM) mm Hg, compared to a PaCO2 of 35 +/- 1 in the other 43 patients. There were no differences between the 2 groups in the number or duration of nocturnal obstructive events. In contrast, the hypercapnic patients were significantly heavier than the normocapnic patients (body weight, 189 +/- 11 versus 148 +/- 6% of ideal; p less than 0.005) and had evidence of diffuse airway obstruction, as indicated by an increased residual volume and a reduction in all expiratory flow rates. When the hypercapnic patients were compared with a weight-matched group of 9 normocapnic patients (body weight, 196 +/- 8% of ideal), there were still no differences in nocturnal obstructive events, but the differences in tests of airway mechanics persisted. Multiple regression analysis of PaCO2 against several anthropometric, respiratory physiologic, and polysomnographic variables revealed that only 2 variables (expiratory reserve volume and FEV1/FVC), both of which are influenced by airway mechanics, were significantly correlated with PaCO2 (multiple r = 0.78; p = 0.0001). The findings suggest that OSA alone does not produce daytime hypercapnia even in obese patients, and that the presence of diffuse airway obstruction is an important predisposing factor to the development of chronic CO2 retention in such patients.     

Hypoxic and hypercapnic ventilatory responses in awake children with congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS) has been thought to be a disorder of central chemoreceptor responsiveness. Previous studies in CCHS have shown decreased or absent ventilatory responsiveness to both hypercarbia and hypoxia. However, hypoxic responsiveness during wakefulness has not been systematically studied. We studied hypoxic and hypercapnic ventilatory responses during wakefulness in five children with CCHS (6 to 11 yr of age). To measure the hypercapnic response, the children rebreathed a hyperoxic hypercapnic mixture until PaCO2 reached 56 to 69 mm Hg. For the hypoxic response, the children rebreathed a hypoxic gas mixture, at mixed venous PCO2, until SaO2 had fallen to less than 78%. We found that the ventilatory responses to hypercapnia and hypoxia were very variable (linear correlation coefficients ranging from -0.44 to +0.63 for hypercapnic responses and from -0.15 to +0.77 for hypoxic responses), with no significant change from baseline in response to either stimulus. There was no evidence of progressive ventilatory stimulation despite increasing stimulus. Additionally, these children had no subjective sensation of dyspnea or discomfort. This establishes that hypoxic and hypercapnic ventilatory control is absent during wakefulness. Chemoreceptor control (peripheral and central) is, therefore, defective in all states in children with CCHS. We speculate that the defect in CCHS lies in central integration of the central and peripheral chemoreceptor signals.     

Effect of Bedtime Alcohol on Inspiratory Resistance and Respiratory Drive in Snoring and Nonsnoring Men

We measured inspiratory resistance (R₁), inspiratory occlusion pressure (P_0–1), and the ventilatory responses to hypercapnia and isocapnic hypoxia during waking and during stage 2 non-rapid eye movement sleep in nine young men who were habitual snorers. They were studied on 2 nights during the 3 hours after receiving a bedtime drink containing either a placebo or 100-proof vodka (1.5 ml/kg) in orange juice. We compared the results with those we reported previously in 10 nonsnoring but otherwise similar men. Waking R₁ was the same in nonsnorers and snorers, and it was not affected by ethanol. During sleep on the control night, R₁ increased by 70% in nonsnorers and by 280% in snorers. On the ethanol night, the increase from waking to sleeping was more than doubled in both nonsnorers and snorers. P_0–1 and the responses to hypercapnia and hypoxia showed no differences between nonsnorers and snorers, therefore the results from the two groups were pooled. Minute ventilation and the hypercapnic response decreased from waking to sleeping and P_0–1 was more negative during sleep, but there was no significant effect of ethanol. There was a significant correlation between the changes from waking to sleeping in R₁ and P_0–1 on the ethanol night suggesting that inspiratory effort increased in response to the increased resistance. The response to isocapnic hypoxia showed no effect of either sleep state or drink. lnspiratory time did not change but mean inspiratory flow (V_T/t₁) was significantly reduced during sleep on both control and ethanol nights. The duty cycle ratio (T₁/T_tot) was significantly increased during sleep on the ethanol night. Despite its great effect on inspiratory resistance, especially in snorers, ethanol, in the dose used in our study, does not augment the depression of minute ventilation or of the hypercapnic response that occur normally in stage 2 non-rapid eye movement sleep. After ethanol, our subjects showed the decreased Vt/T_i and the increased T_i/T_tot that occur normally during sleep in response to an inspiratory resistive load. However, they also showed increased inspiratory effort. The combination of increased inspiratory resistance and greater inspiratory effort would increase the tendency of an unstable upper airway to collapse and could account for the aggravation of obstructive sleep apnea by ethanol.     

Alveolar pressure and airway resistance during maximal and submaximal respiratory efforts

A digital computing technique was used to extract continuous calculations of average alveolar pressure and airway resistance from body plethysmographic measurements during forced inspiratory and expiratory vital capacity maneuvers and tidal breathing in human subjects. Derived alveolar pressures were similar to those obtained using an interrupter technique (linear regression slope, 0.99 +/- 0.02; r = 0.98) and by comparison with esophageal pressure measurements. Studies in normal subjects revealed a characteristic pattern of increasing airway resistance throughout the expiratory phases of maximal and submaximal respiratory maneuvers, with maximal resistance of 33 to 110 cm H2O/L/s at low lung volumes during forced vital capacities. In contrast, inspiratory resistance remained low and constant throughout maximal and submaximal inspiratory maneuvers. Patients with COPD showed substantially higher inspiratory and expiratory resistances. In three patients with flow-volume loops suggestive of variable extrathoracic upper airway obstruction, measurements of alveolar pressure and airway resistance made it clear that two of the patients had upper airway obstruction, whereas the other was exerting an inadequate effort. We conclude that this noninvasive technique provides valid estimates of alveolar pressure and airway resistance continuously throughout both phases of the respiratory cycle over a wide range of volumes and flow rates. It may prove to be useful in the assessment of effort and airway obstruction in patients with a variety of pulmonary conditions.     

The role of catecholamines in regulating arterial oxygen content during acute hypercapnic acidosis in rainbow trout (Salmo gairdneri)

The involvement of catecholamines in regulating arterial oxygen content (CaO2) during hypercapnic acidosis in rainbow trout (Salmo gairdneri) was investigated by comparing physiological responses during acute normoxic hypercapnia (a condition in which plasma epinephrine is elevated) and acute hyperoxic hypercapnia (a condition in which plasma epinephrine is not elevated). Red blood cell pH (rbc pH) was maintained significantly higher in the normoxic hypercapnic fish despite similar reductions in whole blood pH (pHe) in both groups. Elevation of rbc pH in the normoxic hypercapnic fish was abolished by pre-treatment with the beta-adrenoceptor antagonist, propranolol, whereas injection of epinephrine into hyperoxic hypercapnic fish significantly raised rbc pH. Arterial blood oxygen carrying capacity increased only in the normoxic hypercapnic fish due to significant increases in blood haemoglobin (Hb) levels. The ability of trout to elevate blood Hb was abolished by pre-treatment with the alpha-adrenoceptor antagonist, phentolamine. Injections of epinephrine into normocapnic fish caused increases in blood Hb and concomitant decreases in spleen wet weight and Hb content. Adrenergic elevation of blood Hb was not observed in splenectomized fish. CaO2, although depressed during normoxic hypercapnia, was indeed regulated when compared to CaO2 values predicted from the in vitro Root effect. Pre-treatment with phentolamine, but not propranolol, abolished the ability of trout to regulate CaO2.