Effects of sleep-induced increases in upper airway resistance on ventilation

To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined effects of female hormones and metabolic rate on ventilatory drives in women

Increased resting ventilation (VE) and hypoxic and hypercapnic ventilatory responses occur during pregnancy in association with elevations in female hormones and metabolic rate. To determine whether increases in progestin, estrogen, and metabolic rate produced a rise in VE and hypoxic ventilatory response (HVR) similar in magnitude to that observed at full-term pregnancy, we studied 12 postmenopausal women after 1 wk of treatment with placebo, progestin (20 mg tid medroxyprogesterone acetate), estrogen (1.25 mg bid conjugated equine estrogens), and combined progestin and estrogen. Progestin alone or with estrogen raised VE at rest and decreased end-tidal PCO2 (PETCO2) by 3.9 +/- 0.8 and 3.3 +/- 0.6 Torr, respectively (both P less than 0.05), accounting for approximately one-fourth of the rise in VE and three-fourths of the PETCO2 reduction seen at full-term pregnancy. The addition of mild exercise sufficient to raise metabolic rate by 33-36% produced the remaining three-fourths of the rise in VE but no further decline in PETCO2. Combined progestin and estrogen raised HVR and hypercapnic ventilatory response more consistently than progestin alone and could account for one-half of the increase in HVR seen at full-term pregnancy. Mild exercise alone did not raise HVR, but when exercise was combined with progestin and estrogen administration, HVR rose by amounts equal to that seen at full-term pregnancy. We concluded that female hormones together with mild elevation in metabolic rate were likely responsible for the pregnancy-associated increases in VE and HVR.     

Role of neural afferents from working limbs in exercise hyperpnea

To determine the role of reflex discharge of afferent nerves from the working limbs in the exercise hyperpnea, 1.5- to 2.5-min periods of phasic hindlimb muscle contraction were induced in anesthetized cats by bilateral electrical stimulation of ventral roots L7, S1, and S2. Expired minute ventilation (VE) and end-tidal PCO2 (PETCO2) were computed breath by breath, and mean arterial PCO2 (PaCO2) was determined from discrete blood samples and, also in most animals, by continuous measurement with an indwelling PCO2 electrode. During exercise VE rose progressively with a half time averaging approximately 30 s, but a large abrupt increase in breathing at exercise onset typically did not occur. Mean PaCO2 and PETCO2 remained within approximately 1 Torr of control levels across the work-exercise transition, and PaCO2 was regulated at an isocapnic level after VE had achieved its peak value. Sectioning the spinal cord at L1-L2 did not alter these response characteristics. Thus, reflex discharge of afferent nerves from the exercising limbs was not requisite for the matching of ventilation to metabolic demand during exercise.     

Effects of adenosine on ventilatory responses to hypoxia and hypercapnia in humans

Adenosine infusion (100 micrograms X kg-1 X min-1) in humans stimulates ventilation but also causes abdominal and chest discomfort. To exclude the effects of symptoms and to differentiate between a central and peripheral site of action, we measured the effect of adenosine infused at a level (70-80 micrograms X kg-1 X min-1) below the threshold for symptoms. Resting ventilation (VE) and progressive ventilatory responses to isocapnic hypoxia and hyperoxic hypercapnia were measured in six normal men. Compared with a control saline infusion given single blind on the same day, adenosine stimulated VE [mean increase: 1.3 +/- 0.8 (SD) l/min; P less than 0.02], lowered resting end-tidal PCO2 (PETCO2) (mean fall: -3.9 +/- 0.9 Torr), and increased heart rate (mean increase: 16.1 +/- 8.1 beats/min) without changing systemic blood pressure. Adenosine increased the hypoxic ventilatory response (control: -0.68 +/- 0.4 l X min-1 X %SaO2-1, where %SaO2 is percent of arterial O2 saturation; adenosine: -2.40 +/- 1.2 l X min-1 X %SaO2-1; P less than 0.01) measured at a mean PETCO2 of 38.3 +/- 0.6 Torr but did not alter the hypercapnic response. This differential effect suggests that adenosine may stimulate ventilation by a peripheral rather than a central action and therefore may be involved in the mechanism of peripheral chemoreception.     

Influence of inspiratory assistance on ventilatory control during moderate exercise

In five healthy subjects, we studied the effects of controlled mechanical unloading of the respiratory system on ventilatory control during moderate exercise, utilizing a modified positive-pressure ventilator (IEEE Trans. Biomed. Eng. BME-33: 361-365, 1986). We were especially interested in whether isocapnia was maintained when a portion of the normal ventilatory response to constant-load cycling was subserved by the ventilator. The mechanical unloading was achieved by "assisting" airflow throughout inspiration in a constant proportion to instantaneous flow. Two modest degrees of assistance (A1 = 1.5 and A2 = 3.0 cmH2O X l-1 X s) were imposed. The assistance caused minute ventilation (VE) to increase immediately (inspiratory time shortening and tidal volume rising) and end-tidal PCO2 (PETCO2) to fall. Some 10-15 s later, inspiratory occlusion pressure (P100) decreased, and in the new steady-state VE and PETCO2 were virtually restored to their control exercise levels. The modest residual hyperventilation [delta PETCO2 = -0.9 Torr (A1) and -1.6 Torr (A2)], which was not significant statistically, contrasted markedly with the much larger increase predicted for VE had there been no compensatory reduction in ventilatory drive (as evidenced by the fall in P100). Consistent with earlier studies utilizing resistive loading (J. Appl. Physiol. 35: 361-366, 1973 and Acta Physiol. Scand. 120: 557-565, 1984), these observations suggest that ventilatory drive during moderate exercise is controlled to compensate for modest changes in respiratory-mechanical load, so that VE is preserved at a level appropriate to metabolic rate or nearly so.     

Influence of body CO2 stores on ventilatory dynamics during exercise

Pulmonary CO2 flow (the product of cardiac output and mixed venous CO2 content) is purported to be an important determinant of ventilatory dynamics in moderate exercise. Depletion of body CO2 stores prior to exercise should thus slow these dynamics. We investigated, therefore, the effects of reducing the CO2 stores by controlled volitional hyperventilation on cardiorespiratory and gas exchange response dynamics to 100 W cycling in six healthy adults. The control responses of ventilation (VE), CO2 output (VCO2), O2 uptake (VO2), and heart rate were comprised of an abrupt increase at exercise onset, followed by a slower rise to the new steady state (t1/2 = 48, 43, 31, and 33 s, respectively). Following volitional hyperventilation (9 min, PETCO2 = 25 Torr), the steady-state exercise responses were unchanged. However, VE and VCO2 dynamics were slowed considerably (t1/2 = 76, 71 s) as PETCO2 rose to achieve the control exercise value. VO2 dynamics were slowed only slightly (t1/2 = 39 s), and heart rate dynamics were unaffected. We conclude that pulmonary CO2 flow provides a significant stimulus to the dynamics of the exercise hyperpnea in man.     

Effects of altered CSF [H+] on ventilatory responses to exercise in the awake goat

We investigated the effects of selective large changes in the acid-base environment of medullary chemoreceptors on the control of exercise hyperpnea in unanesthetized goats. Four intact and two carotid body-denervated goats underwent cisternal perfusion with mock cerebrospinal fluid (CSF) of markedly varying [HCO-3] (CSF [H+] = 21-95 neq/l; pH 7.68-7.02) until a new steady state of alveolar hypo- or hyperventilation was reached [arterial PCO2 (PaCO2) = 31-54 Torr]. Perfusion continued as the goats completed two levels of steady-state treadmill walking [2 to 4-fold increase in CO2 production (VCO2)]. With normal acid-base status in CSF, goats usually hyperventilated slightly from rest through exercise (-3 Torr PaCO2, rest to VCO2 = 1.1 l/min). Changing CSF perfusate [H+] changed the level of resting PaCO2 (+6 and -4 Torr), but with few exceptions, the regulation of PaCO2 during exercise (delta PaCO2/delta VCO2) remained similar regardless of the new ventilatory steady state imposed by changing CSF [H+]. Thus the gain (slope) of the ventilatory response to exercise (ratio of change in alveolar ventilation to change in VCO2) must have increased approximately 15% with decreased resting PaCO2 (acidic CSF) and decreased approximately 9% with increased resting PaCO2 (alkaline CSF). A similar effect of CSF [H+] on resting PaCO2 and on delta PaCO2/VCO2 during exercise also occurred in two carotid body-denervated goats. Our results show that alteration of the gain of the ventilatory response to exercise occurs on acute alterations in resting PaCO2 set point (via changing CSF [H+]) and that the primary stimuli to exercise hyperpnea can operate independently of central or peripheral chemoreception.     

Effect of beta-adrenergic blockade during exercise on ventilation and gas exchange.

The ventilatory effects of beta-adrenergic blockade during steady-state exercise were studied in eight normal subjects using intravenous propranolol hydrochloride (0.2 mg/kg). Heart rate decreased in all subjects by an average of 17%. Coincident with the phase of decreasing heart rate was a significant decrease in both minute ventilation (VE) and CO2 output (VCO2), averaging 9.6 and 9.2%, respectively. Both functions returned to prepropranolol levels after heart rate had reached its reduced steady-state value. The change in VE was significantly correlated with the change in VCO2 (r = 0.85, P less than 0.005), and was associated with negligible changes in endtidal CO2 tensions and ventilatory equivalents for CO2. We interpret these studies as showing that the transient isocapnic hypopnea concomitant with an acute reduction in cardiac output was secondary to a transient decrease in CO2 flux (cardiac output x mixed venous CO2 content). This decrease in VE appears to be induced by the acute decrease in cardiac output ("cardiodynamic hypopnea"), in fashion similar to the previously described cardiodynamic hyperpnea.     

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.     

Determinants of poststimulus potentiation in humans during NREM sleep.

To test whether active hyperventilation activates the "afterdischarge" mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.     

Effect of dopamine on transient ventilatory response to exercise

The effect of exogenous dopamine on the development of exercise hyperpnea was studied. Using a bicycle ergometer, five subjects performed repetitive square-wave work-load testing from unloaded pedaling to 80% of each subject's estimated anaerobic threshold. The breath-by-breath ventilation (VE), CO2 production (VCO2), and O2 consumption (VO2) responses were analyzed by curve fitting a first-order exponential model. Comparisons were made between control experiments and experiments with a 3-micrograms X kg-1 X min-1 intravenous infusion of dopamine. Steady-state VE, VCO2 and VO2 were unchanged by the dopamine infusion, both during unloaded pedaling and at the heavier work load. The time constants for the increase in VE (tau VE) and VCO2 (tau CO2) were significantly (P less than 0.05) slowed (tau VE = 56.5 +/- 16.4 s for control, and tau VE = 76.4 +/- 26.6 s for dopamine; tau CO2 = 51.5 +/- 10.6 s for control, and tau CO2 = 64.8 +/- 17.4 s for dopamine) (mean +/- SD), but the time constant for VO2 (tau O2) was not significantly affected (tau O2 = 27.5 +/- 11.7 s for control, and tau O2 = 31.0 +/- 10.1 s for dopamine). We conclude that ablation of carotid body chemosensitivity with dopamine slows the transient ventilatory response to exercise while leaving the steady-state response unaffected.     

Effects of CO2 breathing on ventilatory response to sustained hypoxia in normal adults

The relationship between CO2 and ventilatory response to sustained hypoxia was examined in nine normal young adults. At three different levels of end-tidal partial pressure of CO2 (PETCO2, approximately 35, 41.8, and 44.3 Torr), isocapnic hypoxia was induced for 25 min and after 7 min of breathing 21% O2, isocapnic hypoxia was reinduced for 5 min. Regardless of PETCO2 levels, the ventilatory response to sustained hypoxia was biphasic, characterized by an initial increase (acute hypoxic response, AHR), followed by a decline (hypoxic depression). The biphasic response pattern was due to alteration in tidal volume, which at all CO2 levels decreased significantly (P less than 0.05), without a significant change in breathing frequency. The magnitude of the hypoxic depression, independent of CO2, correlated significantly (r = 0.78, P less than 0.001) with the AHR, but not with the ventilatory response to CO2. The decline of minute ventilation was not significantly affected by PETCO2 [averaged 2.3 +/- 0.6, 3.8 +/- 1.3, and 4.5 +/- 2.2 (SE) 1/min for PETCO2 35, 41.8, and 44.3 Torr, respectively]. This decay was significant for PETCO2 35 and 41.8 Torr but not for 44.3 Torr. The second exposure to hypoxia failed to elicit the same AHR as the first exposure; at all CO2 levels the AHR was significantly greater (P less than 0.05) during the first hypoxic exposure than during the second. We conclude that hypoxia exhibits a long-lasting inhibitory effect on ventilation that is independent of CO2, at least in the range of PETCO2 studied, but is related to hypoxic ventilatory sensitivity.     

Control of ventilation during exercise in patients with central venous-to-systemic arterial shunts

The diversion of systemic venous blood into the arterial circulation in patients with intracardiac right-to-left shunts represents a pathophysiological condition in which there are alterations in some of the potential stimuli for the exercise hyperpnea. We therefore studied 18 adult patients with congenital (16) or noncongenital (2) right-to-left shunts and a group of normal control subjects during constant work rate and progressive work rate exercise to assess the effects of these alterations on the dynamics of exercise ventilation and gas exchange. Minute ventilation (VE) was significantly higher in the patients than in the controls, both at rest (10.7 +/- 2.4 vs. 7.5 +/- 1.2 l/min, respectively) and during constant-load exercise (24.9 +/- 4.8 vs. 12.7 +/- 2.61 l/min, respectively). When beginning constant work rate exercise from rest, the ventilatory response of the patients followed a pattern that was distinct from that of the normal subjects. At the onset of exercise, the patients' end-tidal PCO2 decreased, end-tidal PO2 increased, and gas exchange ratio increased, indicating that pulmonary blood was hyperventilated relative to the resting state. However, arterial blood gases, in six patients in which they were measured, revealed that despite the large VE response to exercise, arterial pH and PCO2 were not significantly different from resting values when sampled during the first 2 min of moderate-intensity exercise. Arterial PCO2 changed by an average of only 1.4 Torr after 4.5-6 min of exercise. Thus the exercise-induced alveolar and pulmonary capillary hypocapnia was of an appropriate degree to compensate for the shunting of CO2-rich venous blood into the systemic arterial circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary control during exercise in the duck

To determine the importance of nonhumoral drives to exercise hyperpnea in birds, we exercised adult White Pekin ducks on a treadmill (3 degrees incline) at 1.44 km X h-1 for 15 min during unidirectional artificial ventilation. Intrapulmonary gas concentrations and arterial blood gases could be regulated with this ventilation procedure while allowing ventilatory effort to be measured during both rest and exercise. Ducks were ventilated with gases containing either 4.0 or 5.0% CO2 in 19% O2 (balance N2) at a flow rate of 12 l X min-1. At that flow rate, arterial CO2 partial pressure (PaCO2) could be maintained within +/- 2 Torr of resting values throughout exercise. Arterial O2 partial pressure did not change significantly with exercise. Heart rate, mean arterial blood pressure, and mean right ventricular pressure increased significantly during exercise. On the average, minute ventilation (used as an indicator of the output from the central nervous system) increased approximately 400% over resting levels because of an increase in both tidal volume and respiratory frequency. CO2-sensitivity curves were obtained for each bird during rest. If the CO2 sensitivity remained unchanged during exercise, then the observed 1.5 Torr increase in PaCO2 during exercise would account for only about 6% of the total increase in ventilation over resting levels. During exercise, arterial [H+] increased approximately 4 nmol X l-1; this increase could account for about 18% of the total rise in ventilation. We conclude that only a minor component of the exercise hyperpnea in birds can be accounted for by a humoral mechanism; other factors, possibly from muscle afferents, appear responsible for most of the hyperpnea observed in the running duck.     

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.     

Increased carotid body hypoxic sensitivity during acclimatization to hypobaric hypoxia

Mechanisms of ventilatory acclimatization to chronic hypoxia remain unclear. To determine whether the sensitivity of peripheral chemoreceptors to hypoxia increases during acclimatization, we measured ventilatory and carotid sinus nerve responses to isocapnic hypoxia in seven cats exposed to simulated altitude of 15,000 ft (barometric pressure = 440 Torr) for 48 h. A control group (n = 7) was selected for hypoxic ventilatory responses matched to the preacclimatized measurements of the experimental group. Exposure to 48 h of hypobaric hypoxia produced acclimatization manifested as decrease in end-tidal PCO2 (PETCO2) in normoxia (34.5 +/- 0.9 Torr before, 28.9 +/- 1.2 after the exposure) as well as in hypoxia (28.1 +/- 1.9 Torr before, 21.8 +/- 1.9 after). Acclimatization produced an increase in hypoxic ventilatory response, measured as the shape parameter A (24.9 +/- 2.6 before, 35.2 +/- 5.6 after; P less than 0.05), whereas values in controls remained unchanged (25.7 +/- 3.2 and 23.1 +/- 2.7; NS). Hypoxic exposure was associated with an increase in the carotid body response to hypoxia, similarly measured as the shape parameter A (24.2 +/- 4.7 in control, 44.5 +/- 8.2 in acclimatized cats). We also found an increased dependency of ventilation on carotid body function (PETCO2 increased after unilateral section of carotid sinus nerve in acclimatized but not in control animals). These results suggest that acclimatization is associated with increased hypoxic ventilatory response accompanied by enhanced peripheral chemoreceptor responsiveness, which may contribute to the attendant rise in ventilation.     

Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise

Seven human spinal cord-lesioned subjects (SPL) underwent electrically induced muscle contractions (EMC) of the quadriceps and hamstring muscles for 10 min: 5 min control, 2 min with venous return from the legs occluded, and 3 min postocclusion. Group mean changes in CO2 output compared with rest were +107 +/- 30.6, +21 +/- 25.7, and +192 +/- 37.0 (SE) ml/min during preocclusion, occlusion, and postocclusion EMC, respectively. Mean arterial CO2 partial pressure (PaCO2) obtained from catheterized radial arteries at 15- to 30-s intervals showed a significant (P less than 0.05) hypocapnia (36.2 Torr) during occlusion and a significant (P less than 0.05) hypercapnia (38.1 Torr) postocclusion relative to a group mean preocclusion EMC PaCO2 of 37.5 Torr. Relative to preocclusion EMC, expired ventilation (VE) decreased during occlusion and increased after release of occlusion. However, changes in VE always occurred after changes in end-tidal PCO2 (mean 41 s after occlusion and 10 s after release of occlusion). In the two subjects investigated during hyperoxia, the VE and PaCO2 responses to occlusion and release did not differ from normoxia. We conclude that the data do not support mediation of the EMC hyperpnea in SPL by humoral mechanisms that others have proposed for mediation of the exercise hyperpnea in spinal cord-intact humans.     

Alveolar gas composition and exchange during deep breath-hold diving and dry breath holds in elite divers

End tidal O2 and CO2 (PETCO2) pressures, expired volume, blood lactate concentration ([Lab]), and arterial blood O2 saturation [dry breath holds (BHs) only] were assessed in three elite breath-hold divers (ED) before and after deep dives and BH and in nine control subjects (C; BH only). After the dives (depth 40-70 m, duration 88-151 s), end-tidal O2 pressure decreased from approximately 140 Torr to a minimum of 30.6 Torr, PETCO2 increased from approximately 25 Torr to a maximum of 47.0 Torr, and expired volume (BTPS) ranged from 1.32 to 2.86 liters. Pulmonary O2 exchange was 455-1,006 ml. CO2 output approached zero. [Lab] increased from approximately 1.2 mM to at most 6.46 mM. Estimated power output during dives was 513-929 ml O2/min, i.e. approximately 20-30% of maximal O2 consumption. During BH, alveolar PO2 decreased from approximately 130 to less than 30 Torr in ED and from 125 to 45 Torr in C. PETCO2 increased from approximately 30 to approximately 50 Torr in both ED and C. Contrary to C, pulmonary O2 exchange in ED was less than resting O2 consumption, whereas CO2 output approached zero in both groups. [Lab] was unchanged. Arterial blood O2 saturation decreased more in ED than in C. ED are characterized by increased anaerobic metabolism likely due to the existence of a diving reflex.     

Peripheral chemoreceptor function after carbonic anhydrase inhibition during moderate-intensity exercise.

The effect of carbonic anhydrase inhibition with acetazolamide (Acz, 10 mg/kg) on the ventilatory response to an abrupt switch into hyperoxia (end-tidal PO2 = 450 Torr) and hypoxia (end-tidal PO2 = 50 Torr) was examined in five male subjects [30 +/- 3 (SE) yr]. Subjects exercised at a work rate chosen to elicit an O2 uptake equivalent to 80% of the ventilatory threshold. Ventilation (VE) was measured breath by breath. Arterial oxyhemoglobin saturation (%SaO2) was determined by ear oximetry. After the switch into hyperoxia, VE remained unchanged from the steady-state exercise prehyperoxic value (60.6 +/- 6.5 l/min) during Acz. During control studies (Con), VE decreased from the prehyperoxic value (52.4 +/- 5.5 l/min) by approximately 20% (VE nadir = 42.4 +/- 6.3 l/min) within 20 s after the switch into hyperoxia. VE increased during Acz and Con after the switch into hypoxia; the hypoxic ventilatory response was significantly lower after Acz compared with Con [Acz, change (Delta) in VE/DeltaSaO2 = 1.54 +/- 0.10 l. min-1. SaO2-1; Con, DeltaVE/DeltaSaO2 = 2.22 +/- 0.28 l. min-1. SaO2-1]. The peripheral chemoreceptor contribution to the ventilatory drive after acute Acz-induced carbonic anhydrase inhibition is not apparent in the steady state of moderate-intensity exercise. However, Acz administration did not completely attenuate the peripheral chemoreceptor response to hypoxia.