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Biomedical subjects

J V Weil

Publications and source records attributed to J V Weil.

At least 91 records · Page 5Linked to original sources
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

Respiratory control in the parents of sudden infant death syndrome victims. Ventilatory control in SIDS parents.

To determine if a familial abnormality in the control of breathing might explain the reasons for the sudden infant death syndrome (SIDS), three groups of parents were studied. The first (N = 8 sets of parents) had one infant die of SIDS (one SIDS), whereas the second (N = 6) had a SIDS victim plus a second child with a "near-miss" occurrence (two SIDS). When compared to the third group (controls), these parents demonstrated no abnormality in the ventilatory response to hypoxia or hypercapnia. Similarly, they had normal respiratory frequency, tidal volume, inspiratory time, and arterial blood gas tensions. We conclude that a familial abnormality in breathing control measured during wakefulness is not the basis for SIDS.

Adult↗
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

CO2 and exercise tidal volume.

In progressive exercise increased tidal volume (VT) accompanies increased ventilation (VE) until a VT plateau is reached. We observed in 13 subjects a correspondence between the arrival of the VT plateau and the anaerobic threshold (AT). To examine this association between a mechanical event (the VT plateau) and a metabolic event (the AT), we changed those variables that change at the AT and looked for changes in VT. We found in 13 subjects that CO2 addition to prevent alveolar hypocapnia during cycle ergometer exercise progressing to exhaustion in 12-15 min significantly elevated the VT plateau (mean increase 4.4%; P less than 0.01) as compared with a spontaneous test that induced a mean end-tidal carbon dioxide tension fall of 5.5 Torr. This VT increase was mediated by a significant increase in inspiratory time (TI; P less than 0.02); both the ratio of TI to the total breath duration (TI/Ttot) and the mean rate of inspired airflow (VT/TI) were unchanged at matched VE. Changing other variables known to change at the AT--blood lactate ion concentration and alveolar oxygen tension--left ventilatory pattern unchanged. These results suggest that hypocapnia in severe exercise measurably lowers the VT plateau in normal man.

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

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

Impaired oxygenation during sleep in excessive polycythemia of high altitude: improvement with respiratory stimulation.

Although polycythemia of high altitude is usually due to excessive hypoxemia, in some patients the hematocrit is elevated out of proportion to the degree of hypoxemia measured awake. One possible explanation is that severe hypoxemia occurs during sleep in these subjects. We therefore monitored oxygen saturation (SaO2), breathing pattern, and electroencephalogram (EEG) during sleep in five normal high-altitude residents and in five patients with excessive polycythemia. The polycythemic patients were studied as part of a placebo--drug double-blind crossover trial of the respiratory stimulant drug medroxyprogesterone acetate (MPA). The polycythemic patients while taking placebo were much more hypoxemic during sleep than the normals (all-night mean SaO2: 79.4 +/- 1.7% versus 87.8 +/- 1.7%, p less than 0.01). Abnormalities in breathing patterns were observed in all the subjects, especially during REM stage sleep. In polycythemic subjects, this resulted in precipitous hypoxemia with SaO2 as low as 50%--70%. Severe hypoxemia was not observed in control subjects despite similar abnormalities in breathing. Significant improvement in nocturnal SaO2 occurred when the polycythemic patients were taking MPA, mean SaO2 rising from 79.4 +/- 1.7% to 83.7 +/- 0.7%, p less than 0.05. Of probably greater importance, MPA largely prevented the precipitous drops in SaO2, mean lowest SaO2 rising from 64.6 +/- 4.7% to 76.0 +/- 2.1% p less than 0.05. The severe decreases in SaO2 during sleep may explain elevations in hematocrit that are out of proportion to the awake SaO2 in man at high altitude. The therapeutic effect of MPA in this condition may be due to amelioration of sleep hypoxemia.

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

Exercise ventilation correlates positively with ventilatory chemoresponsiveness.

To determine the relationship of ventilatory responsiveness to hypoxia and hypercapnia to exercise hyperpnea, these responses and steady-state exercise ventilation (VE) were measured in 16 athletes during light (1/3 VO2 max) and heavy (2/3 VO2 max) exercise. Both the hypoxic and hypercapnic ventilatory responses correlated positively with VE per unit metabolic rate (VE/VCO2) at both exercise levels (P less than 0.05). The contribution of the hypoxic response to normoxic exercise VE was quantified by comparing VE in normoxia to VE during a brief (1 min) exposure to high O2 (PAO2 = 200 Torr). High O2 reduced normoxic exercise VE by a mean of 20% at either exercise intensity. Among individuals this reduction was directly dependent upon the intensity of the hypoxic response, and ranged from 7 to 42% of normoxic VE. After the variable reduction of normoxic VE by hyperoxia, all correlations of ventilatory response with exercise VE were lost except for the correlation of hypercapnic response with heavy exercise VE/VCO2. These findings indicate that the extent of VE in light or heavy exercise is modified by the strength of the hypoxic ventilatory response, and that the hypercapnic response independently correlates with VE during heavy exercise.

Adult↗
PubMed1978

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.

Adult↗
PubMed1978

Excessive polycythemia of high altitude: role of ventilatory drive and lung disease.

Persons residing at high altitude who develop excessive polycythemia are more hypoxemic than normal high-altitude residents. We investigated the causes of hypoxemia in 20 patients with excessive polycythemia residing at an altitude of 3,100 m. Lung disease evidenced by abnormal spirometric features and results of a respiratory questionnaire was present in 10 of 20 patients and resulted in increased alveolar-arterial difference for PO2 [(A-a)PO2]. The excessive hypoxemia in the patients with normal lungs was not due to increased (A-a)PO2. We measured ventilatory responses to hypoxia and to hypercapnia to determine whether blunting of these responses was a cause of this excessive hypoxemia. We found, however, that chemical drives to breathe, although blunted, were the same in patients with polycythemia as in high-altitude control subjects. However, an abnormal breathing pattern was observed; the polycythemic patients had a smaller tidal volume and a greater ratio of dead space to tidal volume than did the normal subjects. In addition, the polycythemic patients had increased minute ventilation on breathing 100 percent O2, whereas the normal subjects did not. Thus, hypoxic depression of ventilation may have been present. Our findings suggested that blunted chemical drives are not causative in this disease, and that some other cause of hypoxemia must be present.

Altitude↗
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↗