Biomedical subjects

C W Zwillich

Publications and source records attributed to C W Zwillich.

At least 73 records · Page 4Linked to original sources

PubMed1983

Effect of breathing route on ventilation and ventilatory drive.

Nasal obstruction is associated with abnormal breathing during sleep. To investigate this we measured ventilation and isocapnic hypoxic and rebreathing hypercapnic ventilatory responses in 9 awake normal men, with and without artificial nasal occlusion. Resting breathing frequency was lower (P less than 0.05) with mouth (12.5 +/- 1.0 [SEM]) than with nose (15.1 +/- 1.3 b/min) breathing, due to prolongation (P less than 0.05) of expiratory time with mouth breathing (mouth 3.25 +/- 0.35, nasal breathing 2.41 +/- 0.37 sec). Resting tidal volume was similar for both routes, thus minute ventilation was lower (P less than 0.01) mouth breathing (8.43 +/- 0.44) compared with nose breathing (9.37 +/- 0.47 L/min). Ventilatory responses were greater with mouth than nose breathing both for hypercapnia (mouth 2.29 +/- 0.21, nose 1.58 +/- 0.18 L/min/mm Hg CO2; P less than 0.01) and for hypoxia (mouth 1.08 +/-0.16, nose 0.91 +/- 0.21 L/min/% SaO2; P = 0.10). In 6 subjects measurements were repeated before and after upper airway lignocaine anaesthesia, which abolished the differences in respiratory timing and drive between the breathing routes. It is suggested that there may be upper airway flow receptors which influence respiratory timing.

Adult↗

PubMed1983

Sexual influence on the control of breathing.

Previous investigation has demonstrated that progesterone, a hormone found in premenopausal women, is a ventilatory stimulant. However, fragmentary data suggest that normal women may have lower ventilatory responses to chemical stimuli than men, in whom progesterone is found at low levels. As male-female differences have not been carefully studied, we undertook a systematic comparison of resting ventilation and ventilatory responses to chemical stimuli in men and women. Resting ventilation was found to correlate closely with CO2 production in all subjects (r = 0.71, P less than 0.001), but women tended to have a greater minute ventilation per milliliter of CO2 produced (P less than 0.05) and consequently a lower CO2 partial pressure (PCO2) (men 35.1 +/- 0.5 Torr, women 33.2 +/- 0.5 Torr; P less than 0.02). Women were also found to have lower tidal volumes, even when corrected from body surface area (BSA), and greater respiratory frequency than comparable males. The hypoxic ventilatory response (HVR) quantitated by the shape parameter A was significantly greater in men [167 +/- 22 (SE)] than in women (109 +/- 13; P less than 0.05). In men this hypoxic response was found to correlate closely with O2 consumption (r = 0.75, P less than 0.001) but with no measure of size or metabolic rate in women. The hypercapnic ventilatory response, expressed as the slope of ventilation vs. PCO2, was also greater in men (2.30 +/- 0.23) than in women (1.58 +/- 0.19, P less than 0.05). Finally women tended to have higher ventilatory responses in the luteal than in the follicular menstrual phase, but this was significant only for HVR (P less than 0.05). Women, with relatively higher resting ventilation, have lower responses to hypoxia and hypercapnia.

Adult↗

PubMed1983

Sleep deprivation and the control of ventilation.

Sleep deprivation is common in acutely ill patients because of their underlying disease and can be compounded by aggressive medical care. While sleep deprivation has been shown to produce a number of psychological and physiologic events, the effects on respiration have been minimally evaluated. We therefore studied resting ventilation and ventilatory responses to hypoxia and hypercapnia before and after 24 h of sleeplessness in 13 healthy men. Hypoxic ventilatory responses (HVR) were measured during progressive isocapnic hypoxia, and hypercapnic ventilatory responses (HCVR) were measured using a rebreathing technique. Measures of resting ventilation, i.e., minute ventilation, tidal volume, arterial oxygen saturation, and end-tidal gas concentrations, did not change with short-term sleep deprivation. Both HVR and HCVR, however, decreased significantly after a single night without sleep. The mean hypoxic response decreased 29% from a slope of 1.20 +/- 0.22 (SEM) to 0.85 +/- 0.15 L/min/% saturation (p less than 0.02), and the slope of the HCVR decreased 24% from 2.07 +/- 0.17 to 1.57 +/- 0.15 L/min/mmHg PCO2 (p less than 0.01). These data indicate that ventilatory chemosensitivity may be substantially attenuated by even short-term sleep deprivation. This absence of sleep could therefore contribute to hypoventilation in acutely ill patients.

Adult↗

PubMed1982

Respiration during sleep in normal man.

Respiratory volumes and timing have been measured in 19 healthy adults during wakefulness and sleep. Minute ventilation was significantly less (p less than 0.05) in all stages of sleep than when the subject was awake (7.66 +/- 0.34(SEM) 1/min), the level in rapid-eye-movement (REM) sleep (6.46 +/- 0.29 1/min) being significantly lower than in non-REM sleep (7.18 +/- 0.39 1/min). The breathing pattern during all stages of sleep was significantly more rapid and shallow than during wakefulness, tidal volume in REM sleep being reduced to 73% of the level during wakefulness. Mean inspiratory flow rate (VT/Ti), an index of inspiratory drive, was significantly lower in REM sleep than during wakefulness or non-REM sleep. Thus ventilation falls during sleep, the greatest reduction occurring during REM sleep, when there is a parallel reduction in inspiratory drive. Similar changes in ventilation may contribute to the REM-associated hypoxaemia observed in normal subjects and in patients with chronic obstructive pulmonary disease.

Adult↗

PubMed1982

Hypoxic ventilatory response decreases during sleep in normal men.

Ventilatory drives are presumed to be important in the maintenance of ventilation during sleep. Although the hypercapnic ventilatory response has been shown to decrease during sleep, the hypoxic ventilatory response (HVR) has not been well studied in humans. We therefore measured the ventilatory response to isocapnic hypoxia in 6 sleeping men. The HVR, measured as the slope of the relation between ventilation and decreasing hemoglobin saturation, was significantly lower in all sleep stages than in wakefulness (1.07 +/- 0.19 SEM L/min/%saturation). The HVR decreased to two thirds of this waking value in non-REM sleep (0.63 +/- 0.09 L/min/%saturation) with a further significant decrease in REM sleep when HVR was less than one third of the waking value (0.33 +/- 0.04 L/min/%saturation). The decreased HVR may help to explain the REM-sleep-related hypoxemia found in normal persons and patients with various cardiovascular diseases.

Adult↗

PubMed1982

Hypoxic ventilatory response during sleep in normal premenopausal women.

Sleep apnea syndromes and nonapneic arterial oxygen desaturation during sleep are reported more commonly in men than in women. Because men have recently been shown to have a considerably reduced hypoxic ventilatory response (HVR) during sleep, we questioned if this finding would apply to women as well. Accordingly, we measured isocapnic hypoxic responsiveness in 6 normal women during wakefulness and all stages of sleep during both follicular and luteal phases of the menstrual cycle. During non-REM sleep, women were found to maintain their waking levels of HVR, measured as the slope of the relationship between ventilation and decreasing hemoglobin saturation. Hypoxic ventilatory response fell to 70% of the awake value during REM sleep, which was a significant change (p less than 0.05). Although HVR tended to be greater in the luteal than in the follicular phase of the menstrual cycle, both awake and asleep, this was significant only in Stage 2 sleep (p less than 0.05). When compared with recently reported men studied in this laboratory, these women demonstrated significantly less awake HVR even when corrected for body surface area (p less than 0.05). During sleep men and women had similar hypoxic responses, although this represents a considerable decrement in the awake response in the men and little change in the women. How these findings relate to the observed sexual differences in "sleep disordered breathing" is speculative.

Adult↗

PubMed1982

Hypercapnic ventilatory response in sleeping adults.

During rapid eye movement (REM) sleep, hypoxia and hypercapnia occur in conjunction with hypoventilation. Although the hypoxic ventilatory response has previously been shown to be reduced in REM sleep, the hypercapnic ventilatory response (HCVR) has not been studied during REM sleep in adult humans. We therefore measured the ventilatory response to hypercapnia in 12 sleeping adults using a modified rebreathing method. The HCVR was significantly reduced in all stages of sleep compared with that during wakefulness (1.60 +/- 0.19 SEM L/min/mmHg CO2), falling to less than half the waking HCVR during non-REM sleep (0.75 +/- 0.08 L/min/mmHg CO2), with a further significant drop during REM sleep when HCVR was less than a third of that during wakefulness (0.45 +/- 0.10 L/min/mmHg CO2). The decreased ventilatory responses to hypercapnia and hypoxia in REM sleep help explain REM-related hypoxemic episodes.

Adult↗

PubMed1982

Central sleep apnea. Improvement with acetazolamide therapy.

Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5 +/- 0.54 mm Hg. This may be important in mediating the observed decrease in apneas.

Acetazolamide↗

PubMed1981

Control of breathing during prolonged exercise.

Ventilation (VE) climbs steadily throughout prolonged heavy exercise. While this VE "drift" has implications for the adequacy of gas exchange in long-term exercise, its mechanism remains unknown. We examined the behavior of previously proposed mediators of VE drift during one hour of cycle ergometer exercise at constant work rate requiring 2/3 VO2 max in 10 subjects. VE increased 13% from 12 to 61 min of exercise (P less than 0.05). Although body core temperature rose as VE rose, equal elevation of core temperature by passive means failed to increase exercise VE. Rising VE during the hour of exercise occurred despite unchanged arterial pH, PCO2, and lactate and despite unchanged VCO2. Thus, all of the VE increase was calculated to be due to increased dead space ventilation (VD). Tidal volume (VT) was unchanged, while VD/VT rose from 0.16 to 0.24 from 12 to 61 min of work (P less than 0.05). These results show that increased body core temperature does not mediate VE drift, and that changes in previously proposed mediators (arterial pH, arterial lactate, and VCO2) are not necessary for a slow VE rise to occur in prolonged heavy exercise.

Body Temperature↗

PubMed1981

Disturbed sleep and prolonged apnea during nasal obstruction in normal men.

Anecdotal observations suggested that poor quality of sleep is a frequent complaint during upper respiratory infections (URI). Nasal obstruction occurs frequently during URI and causes sleep apnea in some infants. Sleep apnea disrupts normal sleep and could explain the complaints of poor sleep quality during URI in adults. Accordingly, 10 normal men had full night recordings of sleep stages and breathing rhythm before and during nasal obstruction. The order of obstructed and nonobstructed nights was randomized after a standard acclimatization night. During nasal obstruction, time spent in the deep sleep stages decreased from 90 +/- 11.2 (SEM) to 71 +/- 12.9 min (p less than 0.05), whereas significantly more time was spent in Stage 1 sleep (p less than 0.03). This loss of deep sleep during obstruction was associated with a twofold increase in sleep arousals and awakening (p less than 0.01) resulting from an increased (p less than 0.02) number of apneas (34 +/-19 during control sleep versus 86 +/- 34 during obstructed sleep). Apneas of 20 to 39 s in duration became 2.5 times more frequent (p less than 0.05) during obstruction. Oxygen saturation was studied in the last 4 subjects using an ear oximeter. Desaturation (SaO2 less than 90%) occurred 27 times during control sleep compared with 255 times during obstructed sleep. These desaturation episodes occurred only during apneas. All men complained of poor sleep quality during nasal obstruction. We concluded that apneas, sleep arousals and awakenings, and loss of deep sleep occur during nasal obstruction and may explain complaints of poor sleep quality during URI.

Adult↗

PubMed1980

Relative selective action of propranolol on cardiovascular and respiratory responses to isoproterenol.

Organ selectivity of beta sympathetic blockade with propranolol was studied in 6 normal men by comparing the cardiovascular and respiration responses during isoproterenol infusions before and after propranolol. Beta sympathetic blockade was achieved with propranolol and was considered present when there was no heart rate (HR) response to isoproterenol during an infusion tenfold greater than that which raised HR 25% during a control period. During blockade there was no change in HR or systolic or diastolic blood pressure during isoproterenol infusions. There was a consistent (p less than 0.05) rise in resting ventilation (+17%), oxygen consumption (+9%), and carbon dioxide production (+15%) with low-dose (raised HR 10% before blockade) isoproterenol infusion during blockade. These respiratory effects of low-dose isoproterenol during cardiovascular blockade were quantitatively similar to that before blockade. With infusion that raised HR 25%, there was a further increase in VE, VO2, and VCO2 before blockade but no further increase during beta blockade. Changes in acid-base status did not explain the increase in VE during blockade. We conclude that there are differences between effectiveness of propranolol blockade of the cardiovascular system and of the respiratory system.

Blood Gas Analysis↗

PubMed1980

Morphine reduces ventilation without changing metabolic rate in exercise.

Morphine reduces ventilation (VE) in exercising man. The mechanism of this ventilatory depression remains unclear. Recent evidence suggests that morphine may reduce exercise VE by simultaneously reducing exercise metabolic rate. We measured exercise VE in six normal subjects after intravenous injection of either saline or 0.1 mg/kg morphine sulfate. During treadmill walks requiring 1/3 and 2/3 of the maximal oxygen uptake, morphine reduced VE (P < 0.05), while it left metabolic rate unchanged. Morphine treatment elevated end-tidal PCO2 at both work levels (P < 0.05). Lower VE and higher PETCO2 in exercise after morphine persisted after elevation of alveolar PO2 to 200 torr. Thus, morphine left unchanged the contribution of the hypoxic chemoreflex to normoxic exercise VE. In addition, morphine failed to alter the ventilatory responses to hypercapnia measured at each exercise level. These results suggest that analgesic dosages of morphine reduce the ventilatory response to exercise through a mechanism other than alterations in metabolic rate or chemical ventilatory responses.

Carbon Dioxide↗

PubMed1979

Influence of exercise hyperthermia on exercise breathing pattern.

Passive elevation of the body core temperature (Tc) induces rapid, shallow breathing in resting man. We wondered if exercise-induced Tc elevation would also lead to decreased tidal volume (VT) and increased breathing frequency (f) during exercise. To investigate this question, 10 subjects each performed 47 min of cycle ergometer exercise at 50--60% of the maximal aerobic capacity, with the work rate adjusted to maintain ventilation (VE) constant. This long ride raised mean Tc (rectal) 0.8 degrees C. Before and immediately after the long ride, ranges of VE and VT were obtained from short 6-min rides that progressed from unloaded pedaling to the anaerobic threshold. At the constant VE of the long ride, f rose and VT fell as Tc rose (P less than 0.05). The fall in VT was associated with a fall in inspiratory time (TI); drive (VT/TI) and timing (TI/Ttot)components of VE were unchanged. These effects were consistent over the entire range of VE obtained from the short 6-min rides. Passive heating in warm water to produce equal Tc elevation in the same subjects yielded similar exercise breathing-pattern changes. These findings suggest that increased Tc mediates the VT fall during prolonged exercise, possibly through stimulation of the central respiratory pacemaker.

Body Temperature↗

PubMed1979

The effects of unanesthetized arterial puncture on PCO2 and pH.

Painful unanesthetized arterial puncture may produce transient hyperventilation, and this hyperventilation might alter resting values of arterial pH and PCO2. We investigated this possibility by comparing pH and PCO2 values of blood samples obtained by arterial puncture with values of arterialized venous blood obtained by a painless method. In 19 consecutive subjects, virtually no difference in pH or PCO2 resulted from an arterial puncture that could not be attributed to the inherent precision of the measuring instrument. Mean +/- SEM pH was identical (7.45 +/- 0.05) both before and during an arterial puncture, as was PCO2 (34.4 +/- 1.2 mm Hg). The variation (SD) in PCO2 within an individual subject was +/- 1.7 mm Hg, which was almost identical to the inherent precision of the Radiometer ABL-2 acid base laboratory (SD, +/- 1.32). We conclude that an unanesthetized arterial puncture provides an accurate measurement of resting pH and PCO2.

Anxiety↗

PubMed1979

Low exercise ventilation in endurance athletes.

Previous studies have shown that endurance athletes are endowed with low ventilatory responses to chemical stimuli. The implications of this association have never been clear. Although recent evidence shows that exercise ventilation (VE) correlates with ventilatory chemoresponsiveness in a group of athletes, the extent to which non-athletes may differ from athletes in this regard is unknown. We have examined the relationship between ventilatory chemoresponsiveness and exercise VE in a group of 7 non-athletes, and contrasted these findings with those obtained previously from 8 endurance and 8 non-endurance athletes. Correlation lines of exercise VE with chemical responses were similar in slope and intercept for both athletes and non-athletes. However, we found that non-athletes had greater exercise VE per unit metabolic rate (VO2 or VCO2), and greater ventilatory responses to O2 and CO2, when compared with endurance athletes at equal relative work loads (P less than 0.05). The lower exercise VE/VCO2 of endurance athletes as compared with non-athletes persisted in hyperoxia, indicating that factors other than differences in hypoxic sensitivity explain the lower exercise VE of endurance athletes. Low exercise VE may be the link between low ventilatory chemosensitivity and outstanding endurance athletic performance.

Adult↗

PubMed1978

Familial aspects of decreased hypoxic drive in endurance athletes.

One difference between endurance athletes and nonathletes is decreased ventilatory responsiveness to hypoxia and hypercapnia. It has never been clear whether these decreased responses are a consequence of conditioning or precede participation in endurance athletics. Recent studies demonstrating clusters of decreased ventilatory responses to hypoxia in families of patients with unexplained respiratory failure suggest that decreased responses in endurance athletes might be familial. To investigate this possibility, ventilatory response to hypoxia and hypercapnia were measured in 16 nonathletic, healthy parents and siblings of five successful long-distance runners. Response were compared to 34 nonathletic controls. As measured by the shape parameter A, hypoxic response was decreased to a similar extent in runners 74 +/- 6.4 (mean +/- SE) (P less than 0.05) and their relatives 69 +/- 15.2 (P less than 0.01) compared to control 128 +/- 11.3. Hypercapnic responses were slightly, but not significantly, decreased in runners and their families. We conclude familial influences made a major contribution to the decreased hypoxic ventilatory response seen in long-distance runners.

Adolescent↗

PubMed1978

The effects of smoked marijuana on metabolism and respiratory control.

Marijuana is a sedative, and most sedatives are respiratory depressants. However, the ventilatory effects of marijuana are unknown. In a placebo-controlled study of 8 subjects, smoking marijuana significantly increased ventilation and hypercapnic ventilatory response. Peak effects occurred 15 min after smoking, when ventilation increased from 7.4 +/- 0.39 (mean +/- SE) to 10.4 +/- 1.41 liter per min (P less than 0.01), whereas hypercapnic ventilatory response, measured as the slope of the relationship of ventilation to CO2, increased from 2.7 +/- 0.28 to 5.4 +/- 1.02 liter per min per mm Hg (P less than 0.05). Blood pH, PCO2, and ventilatory response to hypoxia were unchanged. Changes in ventilation usually parallel changes in metabolic rate. Smoked marijuana caused an increase in metabolic rate that also peaked after 15 min. Pretreatment with propranolol completely abolished the increase in hypercapnic ventilatory response, but did not affect the other changes. Thus, smoked marijuana had stimulatory effects on metabolic rate, ventilation, and the ventilatory response to CO2. The latter appears to be mediated by the beta sympathetic nervous system.

Cannabis↗

PubMed1978

Hereditary aspects of decreased hypoxic response.

Decreased ventilatory responses to hypoxia and hypercapnia have been demonstrated in a variety of disorders; however, the etiology of these decreased drives remains virtually unknown. Recent observations have suggested a familial influence on hypoxic and hypercapnic ventilatory response, but it is unclear whether this influence is the result of hereditary or environmental influences. Therefore we measured the ventilatory response to isocapnic hypoxia (HVR) and hyperoxic hypercapnia in 12 pairs of identical and 12 pairs of nonidentical twins. Significant correlation (P less than 0.01) was found for HVR within identical twin pairs but not within nonidentical twin pairs. Identical twins resembled each other more closely with respect to HVR than was the case for nonidentical twins (P less than 0.0125). This was independent of body size, blood PCO2, or pH. No such correlation could be found for ventilatory response to hyperoxic hypercapnia. It is concluded that hereditary influences affect HVR and it is speculated that such influences may play a role in clinical conditions characterized by decreased hypoxic ventilatory responses.

Adolescent↗