[Effect of smoking on carboxyhemoglobin and erythrocyte filtration].
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Biomedical subjects
Publications and source records attributed to C Guillot.
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1 Concentration-effect curves to acetylcholine and histamine were produced in fresh human bronchial muscle (2 to 4 h after removal from the patients) and in preparations previously stored at 4 degrees C for 12 h. 2 Sensitivities of fresh human airway muscle preparations to acetylcholine (pD2 value, 5.89 +/- 0.03; n = 4) and histamine (pD2 values, 5.41 +/- 0.03; n = 13) were similar. There was no significant difference in the sensitivities of stored preparations (acetylcholine: pD2 value, 5.70 +/- 0.06; n = 23 and histamine: pD2 value, 5.44 +/- 0.07; n = 16) when compared to the fresh preparations. 3 Indomethacin did not significantly change the basal tone in preparations of either fresh or stored human airway muscle. 4 A low concentration of indomethacin (0.17 muM) significantly reduced responsiveness and sensitivity to histamine in stored bronchi but not in fresh bronchi. The acetylcholine concentration-effect curves were unaltered by exposure to this concentration of indomethacin in either fresh or stored tissues. High concentrations (1.7 muM and 17 muM) depressed the maximal responsiveness of the bronchi to both agonists. 5 These results suggest indirectly that the regulatory role of prostaglandins in human airway muscle may be different from that in other species.
Among 2,069 patients subjected to pulmonary function tests, 20% were smokers with a mean oxyhemoglobin (HbCO) level of 5.2%. Similar values for HbCO (2.4%) were found in non-smokers and ex-smokers. A positive correlation was observed between daily tobacco consumption and HbCO level, i.e. HbCO = 0.123 (g/day) + 3.433. For a similar consumption (16 g/day), smokers who inhaled the smoke had a significantly higher level of HbCO than smokers who did not (5.8 vs. 4.7%). The interval separating the time when the last cigarette was smoked from HbCO measurement is of utmost importance: for a similar tobacco consumption (10 g/day) HbCO ranged from 6.5 +/- 0.5% when the interval was 1 h to 4.6 +/- 0.3% when it was 3 h (p < 0.005). In some cases, there were discrepancies between the number of cigarettes smoked as indicated by the subjects and the measured levels of HbCO. Possible inhalation of exogenous CO from other sources than smoking or increased production of endogenous CO could account for these differences.
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.
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.
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).
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-).
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.
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.
The ventilatory response to a transient hypercapnia was studied in four awake rabbits maintained in a volume displacement plethysmograph : the increase in inspiratory volume (VI) was associated or not with an increase in inspiratory and expiratory durations (TI and TE). These ventilatory variations were consistent with the activation of the peripheral chemoreceptors by carbon dioxide (short latency of the initial response). After vagal blockade by local anaesthesia, relative ventilatory variations were not significantly different from those previously measured. Central activity seems an important factor reducing inhibitory vagal input and favouring peripheral chemoreceptor afferents.
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.
In 12 normal subjets we studies the effects of beta-adrenergic stimulation (Salbutamol, 500 microgram inhaled) on the closing volume (CV) and the closing capacity and on the ratios of these indexes to the vital capacity (VC) and the total lung capacity, respectively. CV and CV/VC % increased in ten subjects wereas it decreased in two subjects. On an average, the changes were small but significant (p less than 0.01) and could be duplicated in four subjects. Similar studies have yielded variable results. The reasons for those variation could be attributed either to technical or/and individual differences in the resulting effect of beta stimulation on respiratory mechanics.
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.
The individual importance of peripheral chemosensitive afferents was studied using a transient hypercapnia (inhalation of a 5% or a 10% CO2 in air gas mixture respectively during 4 or 2 breaths) in human conscious subjects chosen for their different eupnoeic ventilatory patterns. Calculation of the speed of change in end-tidal CO2 pressure in tracheal gas (sPETCO2) and of the rate of change in tidal volume (sVI) gave assessment for quantifying the sensitivity of arterial chemoreceptors to hypercapnia (sCO2=SVI/SPETCO2). Our results showed that, independently of any outside influence of the eupnoeic ventilatory pattern on the components of the chemical stimulus, sVI and sCO2 were found to be much smaller in subjects whose pattern of breathing was slow (i.e. having a large tidal volume). The possible causes of the weak importance of peripheral chemosensitive afferents in such subjects were discussed.
The relationship between tidal volume (V1) and inspiratory duration (T1) was studied in 5 subjects by a rebreathing procedure in pure O2. The range of this relationship marked by a decrease of T1 with increasing V1, related by Clark and Von Euler to the inhibitory vagal feed-back loop Breuer Hering or B.H. reflex, was only found in 3 subjects possessing the B.H. reflex. In the others, whose pattern of breathing was very slow, nor this range nor the B.H. reflex were found. These findings confirm previous owner data (2). Indeed in our subjects having a slow pattern of breathing, the control of T1 seems to be unrelated to vagal afferences coming from lung stretch receptors.
We determined the lactate concentration in 112 samples of arterial blood, simultaneously by two-different technic: 1) The usual enzymatic technic (plasmatic and intracellular lactates). 2) A new technic using an enzymatic lactate sensor ("lactate analyzer 5400") which measures the plasmatic lactates only. The data obtained with the two technics were very similar (r = 0,982). The small volume of blood used and the handiness and rapidity of the new procedure are to be noted.
The authors studied the tobacco consumption of 283 blood donors and its consequences. 151 were nonsmokers and 132 were smokers (47.7% smoke more than 10 g/day). Their mean HbCO level was 4.3 +/- 0.2% (highest level 15%). HbCO levels are significantly correlated with daily tobacco consumption (p less than 0.001) and can be estimated with the following regression equation: HbCO% = 0.176 (tobacco in grams/day) + 1.976. For a similar consumption, inhalers exhibit significantly (p less than 0.001) higher HbCO levels than noninhalers and the increase is significantly higher (p less than 0.02) in inhalers who smoked 1 h or less prior to blood sampling. High HbCO levels have two consequences: in the donors they have caused a tobacco polycythemia syndrome and in the recipients they have caused acute problems in cases of massive blood transfusion and cardiovascular surgery with extracorporeal circulation.