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Biomedical subjects

C Grimaud

Publications and source records attributed to C Grimaud.

At least 19 recordsLinked to original sources

Transient hypoxia: ventilatory response after vagotomy and during artificial phasic inflation.

The early ventilatory response to transient hypoxia was examined in the anaesthetized rabbit. In intact spontaneously breathing animals, an increase in tidal volume (VT) with an accompanying slight increase in inspiratory duration (TI) and a decrease in the expiratory duration (TE) was observed. After vagotomy, the ventilatory response was distinguished by a greater increase in VT and a significant decrease in TI and TE. In another group of artificially ventilated rabbits, an increase in inspiratory volume with a simultaneous decrease in breathing frequency was found to involve a smaller reflex increase in phrenic inspiratory discharge after onset of transient hypoxia. These observations suggest that afferents from pulmonary vagal stretch receptors inhibit those from arterial chemoreceptors.

Animals

Mechanisms of the bronchoconstrictor effects of deep inspiration in asthmatic patients.

A single deep inspiration (DI) is commonly followed by transient airflow obstruction in asthmatic patients. In some patients, however, DI results in a sustained response which suggests that more than one mechanism may be responsible. We have studied the characteristics of the response to repeated DI, and their modificatiion by various pharmacological agents, by measuring specific airway resistance (sRaw) in ten subjects who showed reproducible and consistent increases in sRaw after DI. Two types of reaction were observed: type A (n = 8) had an immediate maximum and usually short persistence; type B (n = 2) had a delayed maximum with a progressive increase. In type A reactions repetition of DI showed different patterns of response--either a reproducible reaction to each DI or a plateau effect. In type B reactions the response spontaneously increased with repeated DI. Type A responses to DI were inhibited completely by a beta-adrenergic stimulant (BAS), largely by an anticholinergic drug (AC, ipratropium bromide), but in no case by disodium cromoglycate (DSCG). Type B responses were inhibited completely by BAS, largely by DSCG, and partially by AC. These findings suggest that the response to DI is due to bronchoconstriction, which in type A reactions is of reflex origin, vagally mediated, and is due in part or wholly to mediator-release in type B reactions.

Adolescent

[Correlations between the changes in the affinity of hemoglobin of oxygen and the anaerobic metabolism during muscular exercise in 20 silicotic patients (author's transl)].

This study investigated the changes in hemoglobin affinity for oxygen -- P50 standard [P50 (7.40)]; P50 in vivo (P50 IV), and 2,3-diphosphoglycerate concentration (2,3-DPG) -- and the anaerobic metabolism during a short muscular exercise in 20 silicotic patients. P50 (7.40) and 2,3-DPG remained unchanged at the end of the exercise but P50 IV increased significantly. A negative correlation was found between the increase in the arterial lactates and the increase in P50 IV. Such a shift to the right of the oxyhemoglobin dissociation curve probably improves the tissular oxygenation and can be regarded as a compensatory mechanism in patients with pulmonary impairment during exercise.

Diphosphoglyceric Acids

Pattern of the ventilatory response to transient hypoxia in man: differences from transient hypercapnic test.

The pattern of change in ventilatory variables after inhalation of pure N2 for two breaths was studied in normal children and adults. In six subjects the trends of change were compared to the ventilatory response to transient hypercapnia. We observed differences in the patterns of increasing ventilation with an initial abrupt increase of tidal volume for transient hypoxia and a progressive change for hypercapnia. In both cases respiratory frequency was progressively but unsystematically enhanced. A highly significant positive correlation was demonstrated between individual sensitivities to CO2 and O2, with a greater response to hypercapnia (5.6 time) than to hypoxia. Finally, a very short-latency decrease in expiratory duration occurred in the first breath after inhalation of hypercapnic mixture, supporting the recent data of Cunningham et al. (1977).

Adult

[Hemoglobin oxygen combining capacity power. Reproducibility, variability; the effect of carboxyhemoglobin (author's transl)].

Hemoglobin oxygen combining power (HOCP) was measured in blood samples of 41 non smoking subjects and 36 smokers. The reproductibility and the varibility of this value were established (maximal variability was 2,5% in individual measurement). When the oxygen carrying capacity is reported to total hemoglobin (Hbt.), these two groups are not significantly different (1,344 +/- 0,004 ml O2 g-1 Hbt--n = 77-). However, when oxygen carrying capacity is reported to functional hemoglobin (Hbf = Hbt -- HbCO) there is a significative difference between smokers and non smokers (Student's t test 2 p less than 0,001) (1,404 +/- 0,005 ml O2 Hbf -- n = 77-).

Carboxyhemoglobin

[P50 and stored blood (+4 degrees C and -80 degrees C). In vitro studies].

The authors studied the hemoglobin oxygen affinity (P50) and the 2,3 diphospho-glycerate (2,3-DPG) level in: 33 samples of total stored blood (ACD medium); 14 samples of the same blood after mixing with a solution including inosine, pyruvate, phosphate (I.P.P.); 9 samples of freezed erythrocytes. The increase of the hemoglobin oxygen affinity, associated with a decrease of the 2,3-DPG level appears to be very fast in the samples of ACD stored blood since two hours after sampling, the P50 decrease was of 4 torr. Exposure to the I.P.P. solution (1 H at 37 degrees C), caused the hemoglobin oxygen affinity and the 2,3-DPG concentration to return to their normal values (P50 = 25.4 torr +/- 0.4 torr); 2,3-DPG = 15.6 +/- 0.9 muM.gHb-1). When freezed red blood cells, were defreezed the P50 was found to be 4 torr lower than that of fresh blood and the 2,3-DPG level was also decreased (-4.1 muM.gHb-1). These decreases are probably related to the delay which occurred between blood sampling and freezing.

Blood Preservation

[Hemoglobin oxygen affinity in children on chronic hemodialysis].

We have studied the changes induced by hemodialysis in the blood oxygen affinity in a group of 8 children with chronic kidney failure. Before dialysis: the affinity was low - P50 (7.40) = 28,3 Torr. Such a decreased affinity could explain in part why the important anemia (2 million RBC on average) observed in these patients was well tolerated. The observed decrease in hemoglobin oxygen affinity was attributed to an increase in 2-3 diphosphoglycerate (2-3 DPG) concentration, resulting from a high level of inorganic phosphates. After dialysis: the plasmatic pH increased markedly (7.52) with a consequent increase in the blood oxygen affinity in vivo (Bohr effect). No substantial change in 2-3 DPG concentration on P50 (7.40) occurred during hemodialysis.

Adolescent

Bronchial response to inhaled prostaglandin F2alpha in patients with common or aspirin-sensitive asthma.

The effect of aerosolized prostaglandin F2alpha (PGF2alpha) on specific airway resistance (SRaw) has been measured in patients with common (n = 10) or aspirin-sensitive asthma (n = 5). In all subjects PGF2alpha caused a dose-related increase in SRaw, but considerable individual differences in sensitivity were observed. The patients with aspirin intolerance did not differ from regular asthmatics in terms of their response to PGF2alpha. Two types of reactions to PGF2alpha could be distinguished from their time-course: immediate and short-lasting (3 cases) or delayed and long-lasting (12 cases). Inhalation of a beta-adrenergic drug rapidly and completely reversed the effect of PGF2alpha, suggesting that the increase in SRaw was due to bronchospasm. In 7 subjects the inhalation of an anticholinergic drug (SCH 1000) prior to PGF2alpha inhibited to a large extent the effect of the latter, suggesting that the cholinergic system played an important role in the bronchial response to PGF2alpha. In 9 subjects no correlation was found between the bronchial sensitivity to carbachol and PGF2alpha.

Aerosols

Secondary polycythaemia in chronic respiratory insufficiency.

The relationship between polycythaemia, P50 and SaCO (saturation in carboxyhaemoglobin) has been studied in 50 patients who were hypoxaemic due to chronic respiratory insufficiency. These patients were divided into two groups according to their haemoglobin concentration and haematocrit: 21 polycythaemic patients with haemoglobin greater than or equal to 16 g/dl and haematocrit greater than or equal to 50% and 29 patients without polycythaemia. PaO2, PaCO2, plasma and erythrocyte pH, haemoglobin, haematocrit, and carbon monoxide saturation and intraerythrocytic 2-3 diphosphoglycerate concentration were measured during steady-state ventilation. All polycythaemic patients were smokers and their carbon level was significantly higher than that observed in patients without polycythaemia. Additionally, their P50 and 2-3 DPG concentration were significantly lower than in patients without polycythaemia. The correlations between P50 and HbCO and between Hb and HbCO were significant (r=--0-672; r=0-552 respectively: P less than 0-001). Eleven non-polycythaemic patients who were smokers had a high level of HbCO but normal P50. A group of 29 normoxic subjects was also studied, 14 non-smokers and 15 smokers with a high HbCO level. The mean value of P50 was lower in smokers and their haematocrit was higher although the difference was not significant for the latter. The HbCO increase by tobacco seems to be a factor in the occurrence of polycythaemia in patients with chronic respiratory insufficiency. The level of increase of HbCO and/or its duration and perhaps other individual factors and explain why all patients with high HbCO level and hypoxaemia were not polycythaemic.

Carbon Monoxide

Airway response to carbachol in normal and asthmatic subjects: distinction between bronchial sensitivity and reactivity.

By constructing cumulative dose-response curves to inhaled carbachol in 12 normal and 17 asthmatic subjects with comparable baseline specific airway conductance, we have shown that there were wide variations among subjects in the dose of carbachol needed to cause a 25 per cent decrease in specific airway conductance (bronchial sensitivity) and in the slopes of the curves (bronchial reactivity). Furthermore, there was no significant correlation between these 2 characteristics of the bronchial response to carbachol. The mean dose-response curves of the asthmatic and the normal subjects were widely divergent, indicating that the asthmatic subjects differed from normal subjects more in terms of bronchial reactivity than in bronchial sensitivity. This suggests that different mechanisms determine the sensitivity and reactivity of the bronchial tree, and that hyper-reactivity is the main feature of the asthmatic response. Both should be assessed when the bronchial response to bronchoconstrictor agents is measured.

Asthma

Interaction between vagal and chemoreceptors afferents in ventilatory response to transient hypercapnia (anaesthetized rabbit).

In rabbits anaesthetized with ethyl-carbamate, stimulation of chemoreceptors afferents was allowed by transient hypercapnia, before and after vagal blockade by DC current. In these relatively fast breathing animals, the transient hypercapnia produced light changes of inspiratory tidal volume (VI), inspiratory (TI) and expiratory durations (TE). Despite the identity of transient hypercapnia, it ensued that: (1) the higher the spontaneous VI and the lower the respiratory frequency (fR), the greater their respective changes (deltaVI and deltafR) during the ventilatory response; (2) after vagal blockade, greater changes in VI, TI, TE and mean inspiratory flow rate (VI/TI) occurred than in control state, while the relation between deltafR and fR was more significant than in control state. Respective roles played by vagal and chemoreceptors afferents in the ventilatory response to transient hypercapnia are discussed.

Animals

A new simple spirometric index for use with bronchial provocation tests.

Spirometric indices such as the forced expiratory volume in one second (FEV1), the maximal expiratory flow rate (MEFR) and the maximal midexpiratory flow rate (MMFR) can be criticized for use with bronchial provocation tests since they are either partly effort-dependent or dependent on the forced vital capacity (FVC). These criticisms can be avoided by the use of a new index corresponding to the volume of air expired in one second starting at 75% of the control FVC, called the (FEV1)-25. This study was performed to evaluate the relative sensitivity of the (FEV1)-25 and the classical FEV1 in detecting airway obstruction caused by an inhaled carbachol aerosol in 20 asthmatic subjects. The mean fall in (FEV1)-25 of 46% following carbachol inhalation compared with a mean fall in FEV1 of 35% indicates that, in addition to its theoretical advantages, the (FEV1)-25 is a sensitive index for use with bronchial provocation tests.

Adolescent

Effect of short-term, low-level nitrogen dioxide exposure on bronchial sensitivity of asthmatic patients.

Our purpose was to determine whether exposure to a realistic concentration of nitrogen dioxide (NO2) could increase the bronchial sensitivity of asthmatic patients to bronchoconstrictor agents. We established dose-response curves for changes in specific airway resistance (SRaw) in response to aerosolized carbachol in 20 asthmatics after each had spent 1 h in an exposure chamber breathing on one occasion unpolluted air and on a separate occasion 0.1 ppm NO2: sequence of exposures to unpolluted air and to low levels of NO2 were randomized in a single-blind fashion. NO2 induced a slight but significant increase in initial SRaw and enhanced the bronchoconstrictor effect of carbachol in 13 subjects: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.66 mg to 0.36 mg (P less than 0.001). In contrast, NO2 neither modified the initial SRaw nor the bronchoconstrictor effect of carbachol in seven subjects. In 4 out of the 20 subjects, exposure to a higher concentration of NO2 (0.2 ppm) yielded variable results. Potentiation of the carbachol bronchoconstrictor response by NO2 could not be related to any physical or clinical characteristics of the subjects tested. Although the mechanisms underlying the NO2 effect remain controversial, the present results demonstrate that very low levels of NO2 can adversely affect some asthmatics.

Adolescent