Biomedical subjects

J V Weil

Publications and source records attributed to J V Weil.

At least 73 records · Page 4Linked to original sources

PubMed1985

Influence of testosterone on ventilation and chemosensitivity in male subjects.

There is increasing evidence that men have higher ventilatory responses to chemical stimuli than age-matched women and that certain disorders of respiratory rhythmicity, particularly sleep apnea, occur more commonly in men. Accordingly, we studied the influence of the male hormone, testosterone, on the control of breathing. Twelve hypogonadal males were studied at least 30 (mean +/- SE: 69.7 +/- 8.9) days after discontinuing testosterone replacement and again following hormone administration. In each subject plasma testosterone concentration, metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)], minute ventilation (VE), and chemosensitivity [hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses] were determined on and off hormone replacement. With testosterone administration VO2 increased from 248 +/- 15 to 276 +/- 18 ml/min (P less than 0.05), with VCO2 showing a similar but nonsignificant trend. This was associated with an increase in VE from 8.41 +/- 0.78 to 9.91 +/- 0.75 l/min (P less than 0.05) but no change in PCO2. The HVR, expressed as A, increased 44% with hormone replacement from a value of 122 +/- 23 to 176 +/- 28 (P less than 0.01), whereas the HCVR was minimally affected by testosterone administration. These findings may in part explain the previously described differences between male and female subjects in hypoxic sensitivity.

Adult↗

PubMed1985

Hemodynamic response to normovolemic polycythemia at rest and during exercise in dogs.

Very little is known about the influence of polycythemia on oxygen transport during exercise. We studied chronically instrumented dogs trained to run on a treadmill before and after their hematocrit had been increased by isovolemic exchange transfusion with packed red blood cells. With normovolemic polycythemia, cardiac output fell in a linear fashion as hematocrit was increased to 65%, but these changes were balanced by an increasing oxygen content resulting in constant systemic oxygen transport. Oxygen consumption was unchanged both at rest and during exercise after induction of polycythemia. To investigate the effect of polycythemia on oxygen transport further, we measured both mixed venous Po2 and lactate. Mixed venous Po2 increased and lactate remained unchanged both at rest and in exercising polycythemic dogs. Thus, we conclude that, in conscious animals, systemic oxygen transport is well preserved with increasing hematocrit to at least 65%.

Animals↗

PubMed1985

Sleep at high altitude.

The sensation of disrupted sleep following ascent to high altitude is associated with frequent awakenings, which may reflect sleep disruption due to respiratory dysrhythmia consisting typically of monotonously repetitive periodic breathing. This seems to arise from the combined effects of hypocapnia, which leads to suppression of respiratory effort in NREM sleep, and hypoxia, which stimulates termination of apnea and hyperpnea with consequent hypocapnia, leading to perpetuation of periodicity. Sleep disruption and periodic breathing decrease with time at altitude but may also be considerably reduced by pretreatment with acetazolamide, which may act by correction of alkalosis or through some other mechanism. In long-term residents of high altitude less distinctive, undulating respiratory dysrhythmias are described with unstable and decreased arterial oxygenation.

Acclimatization↗

PubMed1985

Noninvasive radioisotopic assessment of pulmonary vascular protein leak. Experimental studies and potential clinical applications.

Noninvasive, double-radioisotope measurement of pulmonary vascular protein leak is a specific and sensitive method for assessing pulmonary vascular permeability. It is sensitive enough to detect increases in vascular protein leak that are too small to produce detectable increases in gravimetric lung water. A simple method for calculating protein leak index reliably reflects expected changes in pulmonary vascular permeability in a broad range of lung injury conditions. This method of measurement may have significant experimental and clinical applications in the study of lung-injury-induced edema, and especially in the evaluation of levels of injury associated with increased permeability but not significant edema. In particular, this method may help to distinguish between increased-permeability edema, such as that which occurs in the adult respiratory distress syndrome, and other types of pulmonary edema in humans.

Animals↗

PubMed1984

Increased metabolism contributes to increased resting ventilation at high altitude.

Ventilatory acclimation to high altitude results in an increase in total or minute ventilation, and is associated with a fall in alveolar PCO2, i.e. alveolar hyperventilation. However, the extent to which the increase in total ventilation is matched by a greater metabolic rate (VO2, VCO2) vs alveolar hyperventilation is unclear. We sought to determine the contribution of changes in metabolic rate to the increase in minute ventilation observed during exposure to high altitude. In 12 healthy male subjects taken from Denver, Colorado (1600 m) to Pikes Peak, Colorado (4300 m) for 5 days, resting minute ventilation increased from low to high altitude (+ 26% for the 5 days) and arterialized PCO2 fell. Resting metabolic rate increased 16% for the 5 days and could account for more than half of the increase in minute ventilation. Among subjects the increases in ventilation on days 1, 2 and 4 were positively correlated with increased CO2 production; they were not correlated with arterial oxygen saturation on any day. During exercise at high altitude, PCO2 values were not different from those at rest and minute ventilation rose above low altitude values (+ 58% by day 5), but the increase could not be accounted for by an increased CO2 production. Thus at rest but not during exercise a substantial portion of the rise in minute ventilation could be attributed to increased metabolic rate.

Acclimatization↗

PubMed1984

Variable inhibition by falling CO2 of hypoxic ventilatory response in humans.

Acute hypoxia stimulates an increase in ventilation but the resulting hypocapnia limits the magnitude of the increase. Thus the hypoxic ventilatory response is usually measured during isocapnia, but this may not reflect events at high altitude. We hypothesized that the degree of inhibition by hypocapnia might depend on individual ventilatory response to CO2 and thus vary between persons. To test this hypothesis we compared the isocapnic hypoxic ventilatory response (end-tidal PCO2 maintained by CO2 addition) with the response in which CO2 was not added and the end-tidal PCO2 fell to a variable extent (poikilocapnic hypoxia). In 14 healthy persons we found that the poikilocapnic hypoxic ventilatory response was determined by two factors: sensitivity to isocapnic hypoxia acting to increase ventilation and sensitivity to CO2 acting to decrease the hypoxic ventilatory response. The ventilatory response to poikilocapnic hypoxia correlated with but was generally less than the isocapnic hypoxic response. The magnitude of the difference between them related to the hypercapnic response. Further, the results suggested that the CO2 response in the high CO2 range related to ventilatory events in the low CO2 range. Thus the magnitude of ventilatory inhibition by hypocapnia may depend on individual ventilatory responsiveness to CO2.

Adult↗

PubMed1984

Hypocapnia and sustained hypoxia blunt ventilation on arrival at high altitude.

Hypoxia at high altitude stimulates ventilation, but inhibitory influences in the first days after arrival limit the ventilatory response. Possible inhibitory influences include hypocapnia and depression of ventilation during sustained hypoxia. Our approach was to compare hypoxic ventilatory responses at low altitude with ventilation at high altitude. In 12 subjects we compared responses both to isocapnic hypoxia and poikilocapnic (no CO2 added) hypoxia during acute (less than 10 min) and sustained (30 min) hypoxia in Denver (1,600 m) with ventilations measured on each of 5 days on Pikes Peak (4,300 m). On Pikes Peak, day 1 ventilation [minute ventilation = 10.0 1/min, BTPS; arterial O2 saturation (Sao2) = 82%] was less than predicted by either acute isocapnic or poikilocapnic tests. However, sustained poikilocapnic hypoxia (Sao2 approximately = 82%) in Denver yielded ventilation similar to that on Pikes Peak on day 1. By Pikes Peak days 4 and 5, endtidal PCO2, pHa, and Sao2 approached plateaus, and ventilation (12.4 1/min, BTPS) on these days was as predicted by the acute isocapnic test. Thus the combination of hypocapnia and sustained hypoxia may have blunted the ventilatory increase on Pikes Peak day 1 but apparently not after 4 or 5 days of acclimatization.

Adult↗

PubMed1984

Temporal delay of venous blood correlates with onset of exercise hyperpnea.

We tested the hypothesis that humoral factors contribute to the onset of exercise hyperpnea in an electrically induced model of isocapnic exercise in alpha-chloralose-anesthetized dogs. A cannula placed in the inferior vena cava (IVC) permitted hindlimb venous blood to flow either directly to the lungs or through a variable-length extracorporeal circuit. Mean transit times (MTT) of blood from exercising hindlimbs were measured from the arrival at the pulmonary artery of green dye injected into the saphenous vein. Onset of hyperpnea was determined by the half time of the ventilatory response (T 1/2), the time required to reach 50% of the steady-state ventilation. In seven dogs, T 1/2 was directly related to MTT (P less than 0.001), suggesting that blood-borne substances released at the onset of exercise contribute to the hyperpneic response. The T 1/2-MTT relation persisted following L2 cord transection (n = 4), suggesting that intraspinal afferents are not required for this response. Chemoreceptor denervation (n = 4) slowed the onset of exercise hyperpnea but did not alter the T 1/2-MTT relation. In this model of electrically induced "exercise" in which neurogenic influences have been minimized, humoral factors alone may stimulate ventilation sufficiently to produce arterial isocapnia.

Animals↗

PubMed1984

Respiratory function in normal Chinese: comparison with Caucasians.

We found that respiratory measurements in Chinese visitors to Colorado differed from those in height- and weight-matched Western residents of Denver, Colo., in the following ways (p less than 0.05): The Chinese had higher respiratory frequencies (15.5 +/- 0.93 vs. 11.4 +/- 0.85 breaths/min), lower tidal volumes (530 +/- 35.9 vs. 693 +/- 477.7 ml), lower alveolar ventilation (4.0 +/- 0.15 vs. 4.7 +/- 0.21 liters), lower forced vital capacities (4.53 +/- 0.16 vs. 5.43 +/- 0.12 liters), lower total lung capacities (6.25 +/- 0.26 vs. 7.16 +/- 0.17 liters), higher resting PaCO2 (36.3 +/- 0.94 vs. 33.6 +/- 0.74 Torr) and lower pHa (7.406 +/- 0.004 vs. 7.419 +/- 0.004). The Chinese also had lower ventilatory responses to CO2 (1.40 +/- 0.10 vs. 2.00 +/- 0.201/min/mm Hg) than did the Caucasians. The measurements made in the Chinese in Denver were similar to those reported for Chinese in China. Thus there may be differences in respiratory function between normal Chinese and normal Western subjects.

Adult↗

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

Right ventricular performance during increased afterload impaired by hypercapnic acidosis in conscious dogs.

Since heart failure may occur in the setting of lung dysfunction and CO2 retention with only modest increases in cardiac work load, we questioned whether myocardial function is impaired by hypercapnic acidosis. To determine the influence of hypercapnic acidosis on right ventricular function, we measured the effects of acute (2 hours) and chronic (2 weeks) hypercapnic acidosis on right ventricular performance during normal and increased right ventricular afterload in five conscious dogs. Systemic hemodynamic and right ventricular functions were unaltered during normal right ventricular afterload by acute hypercapnic acidosis (PaCO2 = 49 +/- 3 mm Hg, pH = 7.27 +/- 0.003). As right ventricular afterload was increased by progressive balloon occlusion of the right ventricular outflow tract during acute hypercapnic acidosis, the rise (slope) in right ventricular end-diastolic pressure was increased 4-fold (P less than 0.01) over that observed in normocapnic control. Maximum isovolumic right ventricular dP/dt rose (P less than 0.05) comparably with increasing right ventricular afterload during normocapnic control and acute hypercapnic acidosis. Chronic hypercapnic acidosis (PaCO2 = 55 +/- 2 mm Hg, pH = 7.28 +/- 0.01) resulted in systemic vasodilation and increased (P less than 0.05) heart rate and cardiac output during normal right ventricular afterload. As right ventricular afterload was increased during chronic hypercapnic acidosis, the rate of rise in right ventricular end-diastolic pressure was 2-fold (P less than 0.01) above normocapnic control but maximum isovolumic right ventricular dP/dt was unchanged in contrast to normocapnic control and acute hypercapnic acidosis. Moreover, cardiac output fell and stroke work was unchanged with increasing afterload during chronic hypercapnic acidosis. beta-Adrenergic blockade resulted in an increased (P less than 0.01) rate of rise in right ventricular end-diastolic pressure with afterload during normocapnic control and chronic hypercapnic acidosis. We conclude that hypercapnic acidosis results in diminished right ventricular performance during increased right ventricular afterload, evidenced by accentuated rise in right ventricular end-diastolic pressure, and may contribute to the congestive heart failure and edema observed in patients with pulmonary hypertension and CO2 retention.

Acidosis, Respiratory↗

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↗

PubMed1983

Lung injury edema in dogs. Influence of sympathetic ablation.

Increased vascular permeability characterizes lung injury pulmonary edema and renders fluid balance in the injured lung especially sensitive to changes in hydrostatic pressure. Pulmonary edema is often associated with increased sympathetic nervous system activity which can lead to pulmonary venoconstriction. This postcapillary venoconstriction could raise microvascular pressure and might therefore increase edema in the injured lung. We produced lung injury edema in dogs with oleic acid and directly measured small (less than 2 mm) pulmonary vein pressure. We found that the small pulmonary vein pressure was increased from 9.8 +/- 0.5 mmHg to 12.6 +/- 0.5 mmHg (n = 10) by oleic acid injury edema. The increase was not due to a rise in left atrial pressure since the small pulmonary vein-left atrial pressure gradient also increased. To test if this increase in the postcapillary pressure gradient was sympathetically mediated, we either unilaterally ablated the stellate ganglion or produced unilateral alpha adrenergic blockade with phenoxybenzamine before giving oleic acid. Both of these "antisympathetic" interventions prevented the increase in pulmonary vein pressure caused by oleic acid edema in the protected lung but not in the intact contralateral lung. These interventions produced a 30 +/- 6.8% reduction in the amount of edema caused by oleic acid. Restoring the increase in small vein pressure by inflating a balloon in the left atrium of dogs with bilateral stellate ganglion ablations abolished the reduction in edema produced by antisympathetic treatment. However, the decrease in edema was not significantly correlated with the reduction in pulmonary vein pressure. Thus, the mechanism of the effects of these antisympathetic interventions remains unclear. We conclude that lung injury edema causes sympathetically mediated pulmonary venoconstriction and that antisympathetic interventions significantly reduce lung injury edema and microvascular pressure.

Animals↗

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↗