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Biomedical subjects

H Gautier

Publications and source records attributed to H Gautier.

At least 55 records · Page 3Linked to original sources

Maturational changes in body temperature and ventilation during hypoxia in kittens.

Developmental changes in body temperature (Tb) and minute ventilation (V) were studied in unanesthetized kittens of 1, 2, 4, 6 and 8 weeks of postnatal age while breathing either air, 11% O2, or 11% O2 + 2.5% CO2. Experiments were mainly carried out at the ambient temperature (Ta) of 26-28 degrees C at which Tb was similar to that measured in the nesting box with the mother and littermates. In air, Tb progressively rose with increasing age to approach adult values by the age of 8 weeks. In hypoxia, Tb significantly decreased relative to room air values at all ages. However, the greatest decline occurred during the first month after birth, whereas by 6 and 8 weeks Tb was only slightly affected by hypoxia. The hypoxic-induced fall in Tb was partially prevented by the addition of 2.5% CO2 to the hypoxic mixture at 1, 2 and 4 weeks and slightly enhanced in the oldest kittens. On the other hand, V was consistently depressed by hypoxia relative to room air in the 1- and 2-week-old kittens. After 4 weeks of age, hypoxia induced a marked and sustained increase in V as in adult cats. Therefore, the depressant effect of hypoxia on body temperature which becomes progressively less effective during the first two months after birth appears to follow a similar postnatal evolution as the ventilatory response to hypoxia. It is suggested that maturity may be a contributing factor to the hypoxic-induced fall in Tb and that the maturational changes in V and Tb in response to hypoxia may be under the influence of the same central mechanisms.

Air↗

Hypoxia-induced changes in shivering and body temperature.

Experiments were carried out on conscious cats to evaluate the general characteristics and modes of action of hypoxia on thermoregulation during cold stress. Intact and carotid-denervated (CD) conscious cats were exposed to ambient hypoxia (low inspired O2 fraction) or CO hypoxia in prevailing laboratory (23-25 degrees C) or cold (5-8 degrees C) environments. In the cold, both groups promptly decreased shivering and body temperature when exposed to either type of hypoxia. Small increases in CO2 concentration reinstituted shivering in both groups. At the same inspired concentration of O2, CD animals decreased shivering and body temperature more than intact cats. While this difference resulted, in part, from a lower alveolar PO2 in CD cats, a difference between intact and CD cats was apparent when the two groups were compared at the same alveolar PO2. During more prolonged hypoxia (45 min), shivering returned but did not reach normoxic levels, and body temperature tended to stabilize at a hypothermic value. Exposure to various levels of hypoxia produced graded suppression of shivering, with the result that the change in body temperature varied directly with inspired O2 concentration. Hypoxia appears to act on the central nervous system to suppress shivering and sinus nerve afferents appear to counteract this direct effect of hypoxia. In intact cats, this counteraction appears to be sufficient to maintain body temperature under hypoxic conditions at room temperature but not in the cold.

Animals↗

Influence of halothane on control of breathing in intact and decerebrated cats.

The effects of halothane anesthesia have been investigated in intact and in decerebrated cats. Pulmonary ventilation and breathing pattern were studied during room-air breathing, hypercapnia, and O2 inhalation. The following results have been demonstrated. First, halothane anesthesia does not modify pulmonary ventilation, but a tachypnea much more intense in intact than in decerebrated cats is observed. This indicates that halothane-induced tachypnea originates mainly in structures rostral to the brain stem. Second, decerebrated animals exhibit a breathing pattern and a ventilatory response to CO2 similar to those of intact conscious cats, suggesting that forebrain facilitatory and inhibitory influences on brain stem are cancelled out by decerebration. However, the tidal volume vs. inspiratory duration relationship observed in decerebrated cats differs from that in conscious cats. Finally, during halothane anesthesia, ventilatory response to CO2 is markedly depressed. Third, during O2 inhalation, except in decerebrated, anesthetized animals, ventilation is only slightly depressed. This suggests that central stimulatory effect of O2 is enhanced and/or that peripheral chemoreceptor drive is reduced.

Anesthesia↗

Hypoxia and monosynaptic reflexes in humans.

The recruitment curves of the monosynaptic Hoffmann (H) reflex and of the direct motor (M) excitation of alpha-motor fibers of the posterior popliteal nerve were studied in seven human subjects in normoxic and hypoxic conditions at sea level. The amplitude of the H and M responses were determined from the computerized full-wave rectified and integrated surface electromyographic (EMG) signal derived from bipolar surface electrodes placed over the soleus muscle. Hypoxic exposure [end-tidal O2 fraction (FETO2) = 0.066 +/- 0.003 and end-tidal CO2 fraction (FETCO2) = 0.0504 +/- 0.001 (SE)] did not affect the maximal M (Mmax) response but decreased significantly (7%) the maximal H (Hmax) response. The Hmax/Mmax ratio decreased from 0.60 to 0.53. Furthermore, by fitting the rising phase of the recruitment curves of the H and M responses vs. stimulus intensity with linear regressions, hypoxia was found to produce a significant decrease of similar magnitude (6%) in the threshold of both the H and M responses with no change in slope. Using a constant stimulus strength eliciting an H response of half the maximum (H50%) of the control conditions, hypoxia resulted in a 50% increase in the amplitude of the H response within 12 min. These results suggest that the effects of hypoxia on the nervous system consist of a direct depolarizing action on the peripheral alpha-fibers and 1A sensory fibers and of a central effect on supraspinal structures affecting the spinal alpha-motoneurons.

Adult↗

Ventilatory response of the conscious or anesthetized cat to oxygen breathing.

In conscious intact cats, oxygen breathing for up to 1 h does not modify ventilation, and the ventilatory response to CO2 in hyperoxia is not consistently decreased. However, oxygen breathing induces sustained hyperventilation in conscious cats after carotid body denervation. In anesthetized cats, oxygen breathing provokes a hypoventilation which is transient under light anesthesia but more sustained under deeper levels of anesthesia. At all levels of anesthesia, the ventilatory response to CO2 is decreased in hyperoxia as compared with normoxia. These results suggest that: the effects of hyperoxia include a central stimulating component, seen only in conscious animals, which offsets the decreased ventilatory drive from peripheral chemoreceptors; this central component is sensitive to anesthesia, thus allowing an explanation for the permanent decrease in ventilation and decrease in ventilatory response to CO2 observed when oxygen is given during deep anesthesia; and anesthesia may help to purposefully unmask factors involved in the control of breathing, but it markedly alters the normal functioning of the respiratory network.

Anesthesia↗

Effects of chronic administration of phenobarbital in low doses on control of breathing in the cat.

The ventilatory response to CO hypoxia (FICO = 0.0025), hypercapnia, and hypoxia was studied in a group of intact, conscious cats before and during chronic administration of phenobarbital (60 mg/day). It was found that the ventilatory response to hypercapnia or hypoxia was not significantly modified during phenobarbital administration. However, the ventilatory response to CO hypoxia was markedly blunted with phenobarbital: the initial ventilatory inhibition was still observed but the subsequent hyperventilation was delayed. Furthermore, the tachypnea was less intense and the decrease in tidal volume was smaller during CO hypoxia. In addition, the behavioral reactions which usually accompanied the tachypnea were attenuated and unconsciousness was often noted. These results indicate that the modifications caused by phenobarbital do not result from a general inhibition of the respiratory control network but rather from a selective inhibition of the structures rostral to the brain stem. As a consequence, the behavioral reactions and resulting respiratory activation were attenuated. Since the hypoxic tachypnea and behavioral reactions are observed only during central hypoxemia, it is concluded that arterial chemoreceptor afferents normally inhibit the supra-pontine structures which are otherwise stimulated by central hypoxemia.

Animals↗

Ventilatory recovery from hypothermia in anesthetized cats.

Ventilation and breathing pattern were recorded in a group of seven anesthetized cats during rewarming from 24 to 38 degrees C of esophageal temperature. It was found that at 24 degrees C, ventilation was very much depressed accounting for an alveolar hypoventilation resulting in hypoxia and hypercapnia. During rewarming, ventilation increased steadily; this was caused by sequential changes in central inspiratory activity (VT/Ti) and Ti/Tt ratio reflecting breath timing. Changes in VT/Ti have been initially attributed to an improvement in chemoresponsiveness and subsequently, to an involvement of supra-pontine thermoregulatory control areas during rewarming. Marked changes in breath timing, especially observed between 28 and 34 degrees C, have been attributed to a direct effect of rewarming upon the brain stem respiratory network. It has the result, that during hypothermia, several components of the respiratory control system are differently affected causing marked changes in breathing pattern and ventilation. They are accompanied by modifications in arterial blood pressure and heart rate.

Animals↗

Chronic ventilatory effects of diazepam and barbiturates in conscious cats.

The chronic ventilatory effects of several hypnotics were investigated in six conscious cats recorded during control periods and during three consecutive days' administration of either diazepam (5 mg), pentobarbital (30 mg) or phenobarbital (60 mg). Ventilation was analyzed in terms of tidal volume (VT), breathing rate (BR) and minute ventilation (V = VT X BR). Minute ventilation was increased with diazepam owing to an increase in breathing rate in spite of a small decrease in tidal volume. With pentobarbital, minute ventilation was not changed because the decrease in breathing rate was compensated for by an increase in tidal volume. With phenobarbital, the results were more variable from one animal to another and on average, only tidal volume was increased. The animals were often excited following the administration of diazepam and sometimes drowsy with pentobarbital; with phenobarbital, behaviour varied among animals. Obviously, the present results cannot be extrapolated if different doses and perhaps different duration of drug administration are used. It is suggested that the ventilatory effects of the drugs cannot be explained only by a direct action on the brain stem respiratory network. Since the level of vigilance was altered by the various drugs, it is proposed that the ventilatory changes observed could be secondary to a supra-pontine action of the drugs which could modify both the level of alertness and respiratory activity.

Animals↗

Developmental changes in ventilation and breathing pattern in unanesthetized kittens.

Ventilation and the breathing pattern of 12 intact, unanesthetized, unrestrained kittens, were recorded at intervals from the second postnatal day to the end of the eighth month. Five of the animals were also studied at 12 months of age. Ventilation (VE) became stable by the 5th month, whereas body weight was still increasing. The relationship between tidal volume (VT) and breathing rate (BR) changed with age. During the 1st month, BR fell and VT increased, VE increasing slowly. From 1 to 5 months, BR remained nearly constant while VT increased. Finally, from 5 to 12 months, BR decreased slightly, VT increased slightly, and VE did not change. The results are compared with relevant data from the literature, especially those derived from interspecific analyses.

Aging↗

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep.

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.

Animals↗

Effects of hypoxia on ventilation during postnatal development in conscious kittens.

Effects of steady-state hypoxia (inspired O2 fraction = 0.11) on ventilation and breathing pattern were studied during postnatal development in unanesthetized kittens. Studies were done from 2 days to 8 mo of age, every week during the first month and every month thereafter. During the first 2 months, states of consciousness were determined. In the first month, minute ventilation (VE) was depressed in hypoxia compared with control values in air, whereas in the older kittens VE was increased in hypoxia, as in adult cats. The inhibitory effect of hypoxia was observed in all three states of consciousness in 7- and 14-day-old kittens. In the 21- and 28-day-old kittens, VE could not be reliably related to the state of consciousness. In the 2-mo-old kittens, VE increased in all states. Tidal volume (VT) was markedly decreased in kittens up to 14 days of age, and respiratory frequency increased. In the 21- and 28-day-old kittens, changes in breathing pattern were variable. In the oldest, the increase of VE was mainly due to an increase of VT. We conclude that in unanesthetized kittens, the ventilatory response to hypoxia is mature at 2 mo of age. The hypoxic tachypnea observed at 7 and 14 days resembles that previously seen in adult carotid-denervated cats, and may be due to a low level of carotid chemoreceptor drive and to a central excitatory effect of hypoxia on respiratory frequency. The complex response observed during the first month of life must reflect the development of peripheral and central mechanisms and their interactions.

Aging↗

[Inoperable primary bronchial cancers: treatment by chemotherapy combinations including cis-platinum].

Sixty-seven assessable patients with advanced primary bronchial carcinoma of the epidermoid or large cell undifferentiated type (37 with non-resectable stage III Mo and 30 with stage III M1) were included in two prospective non-randomized phase 2 chemotherapeutic trials. Thirty-five received a COPAC-type regimen and 32 were treated with a COPAB-RT protocol combining a COPAC-type chemotherapy with local radiotherapy. Both combination therapies contained cis-platinum. With either of these treatments the major response rate averaged 45% and the median survival rate was about 9 months. However, a significant (p = 0.03) difference in survival rate was elicited between the population of treated patients and a control group of 30 untreated patients of similar age, stage and histology (mean survival in controls: 5 months). Both chemotherapeutic regimens were regarded as reasonably well tolerated. These results suggest that platinum-based combination chemotherapy is effective in these carcinomas.

Adult↗

Active and passive respiratory mechanics and control of breathing in kittens.

In five spontaneously breathing kittens (12-13 days old), anesthetized with pentobarbital sodium, we measured the passive and active elastances and resistances of the respiratory system and the decay of inspiratory muscle pressure (PmusI) during expiration. When normalized for body weight (BW), passive resistance (Rrs . BW) was smaller in kittens than in adult cats, whereas passive elastance (Ers . BW) did not differ significantly. As a result, passive time constant (tau rs = Rrs/Ers) was shorter in kittens (mean +/- SE: 0.073 +/- 0.011 s) than in cats (0.121 +/- 0.008 s). This, associated with a faster decay in PmusI in kittens, results in 2-3 times higher flows per kilogram body weight during spontaneous tidal expirations in kittens than in cats. As in the adult cats, the average values of active elastance and resistance were higher than the passive, the average percentage increase amounting to 59 and 49%, respectively. The greater active impedance reflects force-length and force-velocity properties of inspiratory muscles. Its price is higher work of breathing; its advantage is greater intrinsic load compensation.

Airway Resistance↗

Ventilatory response of intact cats to carbon monoxide hypoxia.

Adult intact conscious or anesthetized cats have been exposed to either hypoxia or low concentrations of CO in air. In addition, the ventilatory response to CO2 was studied in air, hypoxic hypoxia, and CO hypoxia. The results show that 1) in conscious cats, low concentrations of CO (0.15%) induce a slight decrease in ventilation and higher concentrations of CO (0.20%) induce first a small decrease in ventilation and then a characteristic tachypnea similar to the hypoxic tachypnea described in carotid-denervated cats; 2) in anesthetized cats, CO hypoxia induces only mild changes in ventilation; and 3) the ventilatory response to CO2 is increased in CO hypoxia in both conscious and anesthetized animals but differs from the increase observed during hypoxia. It is concluded that the initial decrease in ventilation may be caused by some brain stem depression of the respiratory centers with CO hypoxia, whereas the tachypnea originates probably at some suprapontine level. Conversely, the possible central acidosis may account for the potentiation of the ventilatory response to CO2 observed in either conscious or anesthetized animals.

Anesthesia, General↗

Dose effect of pentobarbital sodium on control of breathing in cats.

The dose effect of pentobarbital sodium on integrated ("moving time average") phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR.

Airway Obstruction↗

Pattern of respiration in patients recovering from barbiturate overdose.

Ventilation has been recorded in seven patients who were unconscious following self-poisoning. Measurements were obtained on admission to the hospital and repeated daily until the patients regained consciousness. On admission, recordings were characterized by a low minute ventilation as a result of a low tidal volume in spite of a high frequency of respiration. During the period of recovery tidal volume and minute ventilation increased, whereas frequency decreased. The modifications observed during recovery were the reverse of those noted during the induction of anaesthesia wih barbiturates in man. However, these modifications differ from those observed during induction of anaesthesia in cats. Consequently, as far as respiratory control is concerned, models elaborated in animals cannot be extrapolated to deeply anaesthetized human subjects.

Adult↗

Mechanical properties of the lungs during acclimatization to altitude.

Mechanical properties of the lung were studied in nine healthy lowlanders during a 6-day sojourn at an altitude of 3,457 m. In comparison to sea-level values, it was found at altitude that 1) lung volumes measured by plethysmography including total lung capacity, vital capacity, and functional residual capacity (FRC) presented small changes not exceeding 300 ml; 2) static and dynamic lung compliances were not modified but static pressure-volume curves of lungs were shifted progressively to the left (the decrease in lung elastic recoil averaged about 2 cmH2O on days 4-6); and 3) maximal midexpiratory flow, forced expiratory volume in 1 s, and maximal expiratory and inspiratory flows were increased and, conversely, airways and pulmonary flow resistances were decreased on most days at altitude. The unchanged FRC in the face of a decreased lung recoil may be explained by an increase in thoracic blood volume at altitude, but other possible mechanisms are discussed. The decrease in resistances and increase in maximal flows may be partly explained by the decreased air density at altitude, but another contributing factor such as a bronchodilatation is also suggested. It is proposed that changes in lung mechanics at altitude may account for some of the changes in the pattern of breathing and mouth occlusion pressure (P0.1) observed during acclimatization of lowlanders to altitude.

Acclimatization↗

Hypoxemia, hypercapnia, and breathing pattern in patients with chronic obstructive pulmonary disease.

The results of lung function tests (total and functional residual capacities, residual volume/total lung capacity ratio, forced expiratory volume in one second) breathing patterns and arterial PO2 and PCO2 were studied in 651 ambulatory male patients with chronic obstructive pulmonary disease, functionally and clinically stable. Function tests were only loosely correlated with gas tensions: abnormalities in mechanics and in gas exchange are not necessarily related. In patients matched for the degree of obstruction, the breathing pattern depended upon both PaO2 and PaCO2. Isolated hypoxemia was accompanied by increased respiratory frequency without any variation in tidal volume: this suggests that the chemoreceptive systems still responded to changes in PaO2. Isolated hypercapnia was accompanied by a decrease in tidal volume and an increase in respiratory frequency. Consequently, the dead space/tidal volume ratio increased, leading to a drop in alveolar ventilation and to CO2 retention.

Adult↗