Normal chemoreceptor function in obesity before and after heal bypass surgery to force weight reduction

Ventilatory responses to progressive isocapnic hypoxia and rebreathing of carbon dioxide in oxygen were determined in four obese women before and approximately 1 year after ileal bypass surgery to force weight reduction. None of the patients was hypoventilating and all had normal pulmonary function tests. The ventilatory responses to hypoxia were normal before surgery and were not effected by weight reduction. The ventilatory responses to hypercapnia did not change in slope but a shift of the carbon dioxide response line toward a lower arterial carbon dioxide tension occurred in two subjects after weight reduction. We conclude that obesity per se does not necessarily cause loss of hypoxic ventilatory drive.     

Control of breathing in Duchenne's muscular dystrophy

Duchenne's muscular dystrophy is a progressive degenerative muscular disease which leads to death from respiratory insufficiency in over 80 percent of cases. Recent studies in neuromuscular diseases have suggested that respiratory failure may be of central origin in some of the genetically transmitted neuromuscular diseases. We therefore evaluated the control of breathing in nine patients with advanced Duchenne's muscular dystrophy and compared these patients to nine healthy controls matched on the basis of age, sex and arm span.The purpose of the study was to assess the sensitivity of respiratory centers to hypercapnia, hypoxia and hyperoxia in nine patients with advanced Duchenne's muscular dystrophy. We measured minute ventilation (V?_E), tidal volume (V_T), respiratory frequency (F), mean respiratory flow rate (V_T:T_i) and occlusion pressure (P_0.1) responses as indices of respiratory centers output during hypercapnia (Read's method) and isocarbic hypoxia (Weil's method). We also analysed V?_e during the transient hyperoxia test (Dejours' method). The threshold and magnitude of responses to hypercapnia, hypoxia and hyperoxia were nearly similar in patients and in controls. Patients demonstrated subnormal response of V?_e, V_T:T_i, V_T. Occlusion pressures were nearly the same in normal subjects and in patients with severe muscle weakness. The patterns of responses to those stimuli were markedly different: patients demonstrated a tachypneic pattern of breathing whereas controls preferred to increase their tidal volume.Our study establishes that in patients with advanced Duchenne's muscular dystrophy, the integrity of the carbon dioxide (CO₂) and oxygen (O₂) drive of breathing is well preserved. However in these patients, the pattern of ventilatory response is different from normal. There is a preferential increase in respiratory frequency to hypercapnia and hypoxia stimuli. This tachyphea could well be a clinical manifestation of inspiratory muscle fatigue which resulted in the subnormal ventilatory responses of our patients with Duchenne's muscular dystrophy.     

Respiratory patterns in anesthetised rats before and after anemic decerebration.

Experiments were undertaken to test the comparability of changes in respiratory frequency and tidal volume during hypoxia and hypercapnia in rats with and without intact peripheral chemoreceptors and with intact vagi. Neural organisation of respiratory control was perturbed by anemic decerebration, achieved by ligation of the common carotid and basilar arteries. Ischemia of the brain was produced as far candal as the rostral pontine nuclei involved in respiratory control but left the medulla well perfused. The dominant respiratory effect in animals breathing air or oxygen was polypnea with hypocapnia (mean PaCO2 when breathing air 24.7 mmHg, when breathing oxygen 29.6 mmHg). After decerebration the increase of ventilation produced by breathing 10% O2 in N2 was reduced compared with responses in the intact state but levels of ventilation (V1) in hypoxia were similar to those before decerebration. After decerebration, the increase of ventilation produced by breathing 5% CO2 was greatly reduced and the level of V1 in animals breathing CO2 was significantly less than in the intact state. Intermediate changes were seen in animals breathing 2-3% CO2 which converted the hypocapnia (PaCO2 30.9 mmHg) to eucapnia (PaCO2 46.4 mmHg). In the intact state, hypoxia dominantly caused increased frequency (f) and hypercapnia caused increased tidal volume (VT); after decerebration, hypoxia produced reduction of VT while hypercapnia produced reduction of f. Bilateral carotid sinus nerve section in decerebrate animals eliminated the ventilatory response to hypoxia but left the responses to hypercapnia unaltered. The results point to differences in the mechanisms by which hypoxia and hypercapnia influence respiration in both intact and decerebrate animals with carotid sinus and vagus nerves functional. The differences can now be interpreted in terms of specific neural features of respiratory control.     

Human obesity is characterized by a selective potentiation of central chemoreflex sensitivity.

The chemoreflexes are an important mechanism for regulation of both breathing and autonomic cardiovascular function. Obesity is associated with an increased risk of alveolar hypoventilation and carbon dioxide retention, suggesting that abnormalities in chemoreflex control mechanisms may be implicated. We tested the hypothesis that chemoreflex function is altered in obesity. We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypercapnia, hypoxia, and the cold pressor test in 14 obese subjects and 14 normal-weight subjects matched for age and gender. During hypercapnia, the increase in minute ventilation was significantly greater in obese subjects (7.0+/-0.3 L/min) than in normal-weight subjects (3.3+/-1.1 L/min; P=0.03). Despite higher minute ventilation during hypercapnia in obese subjects, the increase in muscle sympathetic nerve activity was similar in obese and normal-weight subjects. When the inhibitory influence of breathing during hypercapnia was eliminated by apnea, the increase in sympathetic nerve activity in obese subjects (99+/-16%) was greater than in normal-weight subjects (44+/-16%; P=0.02). The magnitude of the ventilatory and autonomic responses to hypoxia and the cold pressor test was similar in obese and normal-weight subjects. We conclude that chemoreflex responses to hypercapnia are potentiated in eucapnic obese subjects. In contrast, responses to hypoxia and to the excitatory cold pressor stimulus in obese subjects are similar to those in normal-weight subjects. Thus, obesity is characterized by selective potentiation of central chemoreflex sensitivity.     

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.     

Prenatal cigarette smoke exposure and postnatal respiratory responses to hypoxia and hypercapnia

Prenatal cigarette smoke (CS) exposure, in combination with hypoxia and/or hyperthermia can lead to gasping and attenuated recovery from hypoxia in 7 days old rat pups. We studied 95 unanesthetized spontaneously breathing 14 days old rat pups to investigate if the destabilizing effects of increased ambient temperature and prenatal CS exposure on respiratory control observed in 7 days old rats were still evident at day 14. This postnatal age was selected as it is beyond the analogous risk period for SIDS in human. Furthermore, we investigated if the breathing responses to hypercapnia are affected by prenatal CS exposure. Since high ambient (HA) temperature can lead to gasping and aberrant respiratory control, we recorded respiratory patterns at low (24-25°C) and high (29-30°C) ambient temperatures, and under hypoxic or hypercapnic states. No gasping was observed in 14 days old rat pups. During hypoxia, breathing frequency increased in the CS-exposed group under low and HA temperatures. Rectal temperature decreased only in the sham group in response to low ambient temperature hypoxia. At HA temperature, breathing frequency increased in both sham and CS-exposed groups during hypercapnia, however, it remained elevated during washout period only in the sham group. We demonstrate that prenatal CS exposure continues to have profound effects on respiratory and thermoregulatory responses to hypoxia and hypercapnia at day 14. The attenuated respiratory and thermoregulatory responses to acute hypoxia and hypercapnia on day 14 demonstrate a strong interaction between CS exposure, respiratory control, and thermoregulation during postnatal maturation.     

VENTILATORY RESPONSES TO HYPOXIA AND HYPERCAPNIA IN ASTHMATICS WITH PREVIOUS RESPIRATORY FAILURE

The ventilatory response to hypoxia and the ventilatory and mouth occlusion pressure response to hypercapnia was measured in 13 subjects who had previously developed respiratory failure or respiratory arrest during an acute asthma attack, In 11 of 12 subjects tested there was a normal response to hypercapnia. Six of the 13 subjects had an impaired response to hypoxia. Impaired hypoxic responsiveness may Contribute to the early onset of hypercapnic respiratory failure during acute severe asthma.     

Vagal feedback is essential for breathing in unanesthetized ground squirrels

The roles of vagal afferent feedback in terminating inspiration and modulating breathing pattern and ventilatory responses to hypoxia and hypercapnia were assessed in the golden-mantled ground squirrel, Spermophilus lateralis, during wakefulness and urethane anesthesia. Hypoxia increased ventilation primarily through increases in breathing frequency (f(R)) while hypercapnia increased ventilation primarily through increases in tidal volume (V(T)) in both anesthetized and unanesthetized animals. Vagotomy resulted in an increase in tidal volume, a decrease in breathing frequency and ventilation, and depressed ventilatory responses to both hypoxia and hypercapnia in anesthetized animals. In unanesthetized animals vagotomy produced a transient 'gasp-like' breathing pattern that rapidly progressed to a non-obstructive central apnea. These data indicate that vagal feedback shapes ventilation on a breath-by-breath basis during anesthesia and is essential for ventilation in unanesthetized animals. The mechanisms that transform the influences of vagal input on breathing between anesthetized and unanesthetized states remain unclear. Changes in breathing pattern induced by the removal of vagal feedback compromise chemoreflexes.     

Effect of unilateral pulmonary vagotomy on respiratory control in man

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.     

Current perspectives on the obesity hypoventilation syndrome

PURPOSE OF REVIEW: Identifying and treating obesity hypoventilation syndrome is an important therapeutic goal, especially given the high morbidity and mortality associated with untreated disease. Significant weight loss or effective treatment of upper airway obstruction will reverse daytime hypoventilation, suggesting that these two mechanisms play key roles in the development and progression of this disorder. Only a subset of morbidly obese patients will develop awake hypercapnia, however, even in the presence of sleep disordered breathing. This implies that complex interplay between a number of known and unknown mechanisms is needed to produce daytime respiratory failure in this patient population. RECENT FINDINGS: Work in the mouse model of obesity has been central in advancing our understanding of the role leptin plays in stimulating ventilation. Leptin deficiency or development of leptin resistance in obesity leads to alterations in central respiratory drive and reduced ventilatory responsiveness, permitting development of carbon dioxide retention. Changes in neuromodulators resulting from the effects of hypoxia may further exacerbate the problem by depressing arousal from sleep in the face of abnormal breathing. SUMMARY: Understanding the various mechanisms contributing to development of obesity hypoventilation is important in order to identify new approaches to effective long-term management of this disorder.     

Alveolar hypoventilation syndrome. Studies of ventilatory control in patients selected for diaphragm pacing

The syndrome of nocturnal hypoventilation and/or apnea without major intrinsic lung disease is of greater surgical interest since the introduction of therapeutic diaphragm pacing. Of our 29 patients successfully managed by diaphragm pacing, we describe 17 in whom detailed studies of the ventilatory responses to hypoxia are available.The diagnosis was established by the following criteria: (1) an increase in arterial carbon dioxide tension (PaCO₂) (> 45 mm Hg) and a depression in the arterial oxygen tension (PaO₂) (< 75 mm Hg) at least during sleep; (2) respiratory arrests and/or apneic episodes during sleep; (3) near normal tests of ventilatory capacity; and (4) diminished ventilatory response to carbon dioxide breathing.New information on the ventilatory responses to hypoxia was obtained by a nonsteady state closed-circuit rebreathing method. The following were compared: (1) hypoxia with carbon dioxide variably absorbed so as to maintain base line PaCO₂ (“normo”-capnic hypoxia); (2) 50 per cent oxygen with carbon dioxide accumulation (hypercapnia hyperoxia); and (3) carbon dioxide accumulation in room air (hypercapnic hypoxia). The data indicate (1) 15 patients showed no measurable ventilatory response to “normo”-capnic hypoxia and two patients showed blunted responses; (2) seven patients showed no ventilatory responses to carbon dioxide whereas 10 patients showed suboptimal increases; (3) combined hypoxia and hypercapnia caused a suboptimal ventilatory response in four patients. These same four patients showed blunted as opposed to absent ventilatory responses to carbon dioxide. (4) Five patients showed no ventilatory responses to all combinations.These 17 patients together with three others not so extensively studied have been managed by nocturnal diaphragm pacing for periods of four months to nearly eight years.We conclude (1) ablation or severe blunting of the ventilatory responses to hypoxia is a frequent and previously underestimated component of this disorder; and (2) diaphragm pacing is an appropriate form of therapy.     

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)     

Clinical complications of obesity

The development of important respiratory disorders and significant hypertension in association with increasing body weight is not widely recognized. Altered respiratory function results from a combination of mechanical impedance to breathing exerted by thoracic and abdominal fat and a ventilation-perfusion mismatch. Sleep-disordered breathing with periods of hypoventilation, with or without apnoeic episodes, may commonly occur in patients with extreme obesity. Nocturnal hypercapnia and hypoxia in such patients may lead to a decrease in ventilatory drive, abnormal central respiratory control and possibly, in time, the development of the obese-hypoventilation syndrome. Respiratory abnormalities should be suspected in obese patients with a history of restlessness at night, loud snoring and daytime somnolence. Treatment is substantial weight reduction, but short-term measures include the use of compressed air via nasal cannulae for obstructive apnoea, and drugs which alter sleep pattern or stimulate respiration. The alterations in endocrine function, which accompany weight gain, may contribute to an increase in blood pressure and there appears to be a relationship between plasma insulin and catecholamine concentrations, fat cell size and the development of hypertension. The confirmation of a raised blood pressure requires that readings be taken with an adequately sized arm-cuff. In many instances endocrine function becomes normal with weight loss, and there is a corresponding decrease in blood pressure. The ideal management for an obese hypertensive patient is the combination of a suitable calorie-restricted diet with a programme of physical exercise.     

Regulation of ventilation before and after sleep in patients with obstructive sleep apnoea

The objective was to examine whether abnormal breathing during sleep may affect regulation of ventilation after awakening in patients with obstructive sleep apnoea (OSAS). In 19 patients with OSA and 12 normal subjects we examined ventilatory responses to hypoxia (HVR) and to hypercapnia (HCVR) before and after sleep (BS and AS), and compared the changes in ventilatory responses with respiratory events during sleep. In the OSA group, the values of resting ventilation were significantly smaller in AS than those in BS and end-tidal partial pressure of CO2 in arterial blood (Pco2) (PETCO2) rose significantly from BS to AS. The slopes of the HVR or HCVR did not differ between BS and AS. However, both the response lines shifted downward and minute ventilation (VE)80 (VE at arterial oxygen saturation (Sao2) of 80%) in HVR and VE60 (VE at PETCO2 of 60 mmHg) in HCVR decreased significantly from BS to AS. The percentage changes of VE80 and VE60 were significantly correlated with mean Sao2, total sleep time below Sao2 of 90% and lowest Sao2 during sleep. However, in normal subjects we observed no circadian variation in their ventilatory responses. These data support the hypothesis that repeated episodes of nocturnal hypoxia and hypercapnia may modify the regulation of ventilation after awakening in patients with OSA.     

Circulating endogenous opioids and ventilatory response to CO2 and hypoxia

The role of endogenous opioids in the control of breathing is not yet well defined. Radioimmunoassays that measure beta-endorphin (BE) and met-enkephalin (MET) having recently become available, we decided to evaluate the possible relation between the blood levels of these two opioids and different hypercapnic and hypoxic ventilatory responses observed in a group of normal subjects. Ventilatory response to hypercapnia (n = 9) and to hypoxia (n = 7) were determined by classical rebreathing methods. A voluntary isocapnic normoxic hyperventilation test was used as a control. Basal levels of BE and MET did not correlate with the magnitude of the ventilatory response to either hypercapnia or hypoxia. Moreover, BE and MET levels measured repeatedly up to 30 min after each test did not change significantly. We conclude that circulating endogenous opioids do not play a role in the control of breathing in normal humans. These results do not rule out a possible role for these substances as locally released mediators.     

Sleep and breathing in Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a genetic disorder, with hypotonia being the predominant feature in infancy, and developmental delay, obesity, and behavioral problems becoming more prominent in childhood and adolescence. Children with this disorder frequently suffer from excessive daytime sleepiness and have a primary abnormality of the circadian rhythm of rapid eye movement sleep. They also have primary abnormal ventilatory responses to hypoxia and hypercapnia, and these abnormalities may be exacerbated by obesity. Children with PWS are at risk of a variety of abnormalities of breathing during sleep, including obstructive sleep apnea and sleep-related alveolar hypoventilation. Clinical evaluation should include a careful history of sleep-related symptoms and assessment of the upper airway and lung function. Polysomnography should be considered for those with symptoms suggestive of sleep-disordered breathing. Treatment options depend on the underlying problem, but may include behavioral interventions, weight control, adenotonsillectomy, and nocturnal ventilation.     

Effect of aminophylline on ventilatory responses in normal man

The bronchodilator effects of aminophylline have been well documented but its effect on ventilatory drives has not been systematically evaluated. Accordingly, the ventilatory responses to hypoxia and to hypercapnia were measured before and after the intravenous administration of 5 mg of aminophylline per kg of body weight to 6 normal subjects. Hypoxic ventilatory response, as measured by an index of the relation between ventilation and hypoxia (parameter A) increased from a mean +/- SE control value of 146 +/- 25 to 254 +/- 35 75 min after the infusion (P less than 0.05). Significant increases in A were also noticed immediately after and 35 and 50 min after the aminophylline infusion. Oxygen consumption increased from a control value of 235 +/- 21 to 263 +/- 21 ml per min STPD (P less than 0.03), and CO2 production increased from 184 +/- 12 to 202 +/- 13 ml per min STPD (P less than 0.01) after aminophylline. Hypercapnic ventilatory response, measured as the slope of the ventilatory response to hypercapnia, was not altered after the aminophylline. Thus, in addition to bronchodilation, the augmentation of the ventilatory response to hypoxia may be a useful factor when this drug is used in acute respiratory failure secondary to airway obstruction.     

Prediction and reversal of blunted ventilatory responsiveness in patients with hypothyroidism

To define the prevalence of impaired ventilatory responses in hypothyroidism, clinical and chemical parameters predicting their presence, and the potential for their acute reversal, ventilatory responses to hypercapnia and hypoxia were studied in 38 hypothyroid patients before treatment, and after short-term (seven days) and long-term (12 to 24 weeks) thyroid hormone therapy. Before treatment, hypercapnic ventilatory responses were blunted in 10 of 29 patients (34 percent), whereas hypoxic ventilatory responses were abnormal in eight of 30 patients (27 percent). Hypothyroid women and patients with marked pretreatment elevation of the serum thyrotropin concentration (greater than 90 mU/liter) were significantly more likely to have impaired ventilatory responses. In patients with an abnormal pretreatment response, parenteral thyroid hormone therapy (25 to 50 micrograms of L-triiodothyronine or 100 micrograms of L-thyroxine per day for seven days) significantly enhanced hypercapnic (0.75 +/- 0.06 to 1.19 +/- 0.16 liters/minute/mm Hg, p less than 0.05) and hypoxic (93 +/- 12 to 176 +/- 31 liters.mm Hg/minute, p less than 0.05) ventilatory responsiveness acutely. In seven of nine patients with abnormal pretreatment hypercapnic responses, and six of eight patients with abnormal hypoxic responses, normal ventilatory responsiveness was restored after one week of therapy. It is concluded that: (1) a subset of hypothyroid patients have blunted ventilatory responses to hypercapnia and/or hypoxia; (2) hypothyroid women and patients with a serum thyrotropin greater than 90 mU/liter more often manifest this abnormality; and (3) thyroid hormone therapy for one week reverses impaired ventilatory responses in hypothyroidism.     

Effects of hypoxia and hypercapnia on aerobic metabolic processes in northern elephant seals.

An hypoxia-induced metabolic down-regulation has been implicated as an important protective mechanism against tissue deoxygenation in mammals. Whether the same response to hypoxia occurs in northern elephant seals was studied. The effects of hypercapnia were also examined to determine whether the reduced ventilatory response of seals to CO2 is associated with an analogous protective metabolic down-regulation. Thirty three seals (7-300-days-old) were studied using open-flow respirometry with simultaneous monitoring of apnea frequencies and heart rates. Hypoxia (11% O2) and hypercapnia (7% CO2) caused increases in metabolism of up to 38% with corresponding decreases in the percent time spent apneic (%AP) and increases in heart rate. The metabolic, breathing and heart rate responses to altered inspired gases were independent of age. Metabolism was strongly negatively correlated with %AP suggesting that elevated metabolism during hypoxia and hypercapnia exposure is attributable to decreases in %AP. In young elephant seals metabolic down-regulation is not an automatic protective response to experimentally-imposed hypoxia or hypercapnia.     

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.