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Biomedical subjects

A Harf

Publications and source records attributed to A Harf.

At least 163 records · Page 9Linked to original sources

Comparison of the effects of fentanyl on respiratory mechanics under propofol or thiopental anaesthesia.

Twenty patients were randomly anaesthetized with either thiopental 5 mg/kg followed by a 15 mg/kg/h continuous infusion, or propofol 2.5 mg/kg followed by a 9 mg/kg/h continuous infusion, paralysed with vecuronium 0.1 mg/kg, intubated and ventilated with nitrous oxide 50% in oxygen. Fifteen minutes after induction, fentanyl 5 micrograms/kg was injected. Inspiratory tracheal pressure (PT), gas flow (V) and volume (V) were continuously measured while the lungs were inflated with a constant inspiratory flow ventilator. Respiratory compliance (Crs) and resistance (Rrs) were calculated from the regression of PT on V. In both groups Crs decreased following anaesthesia. Fentanyl injection elicited an increase in Rrs (from 1.04 +/- 0.70 to 1.63 +/- 0.92 kPa x l-1 x s) and a further decrease in Crs (from 0.55 +/- 0.30 to 0.42 +/- 0.10 l x kPa-1) in the thiopental group but not in the propofol group (Rrs: 1.26 +/- 0.69 to 1.08 +/- 0.44 kPa x l-1 x s, Crs: 0.49 +/- 0.11 to 0.48 +/- 0.13 l x kPa-1). These results suggest that the dose of propofol administered in this study may prevent fentanyl-induced bronchoconstriction.

Adult↗

Influence of tidal volume on histamine-induced bronchoconstriction in guinea pigs.

The effects of tidal volume amplitude on bronchopulmonary reactivity were investigated in three groups of 14 anesthetized paralyzed mechanically ventilated guinea pigs. Animals of group 1 served as control; in animals of group 2, both the sympathetic and parasympathetic nervous systems were blocked; in animals of group 3, only the parasympathetic system was blocked. In each group, the animals were randomly divided into two subgroups characterized by their ventilatory pattern: rate of 60/min with a 6-ml/kg tidal volume or rate of 40/min with a 9-ml/kg tidal volume. Bronchopulmonary reactivity to infused histamine was assessed by the respiratory compliance and conductance values measured during bronchoconstriction and expressed as a percentage of the corresponding basal values. In group 1 the animals ventilated with a 9-ml/kg tidal volume were found significantly less reactive than those ventilated with a 6-ml/kg tidal volume. This difference was abolished in groups 2 and 3. These results demonstrate that the effects of increased tidal volume on bronchopulmonary reactivity are vagally mediated and suggest that the decrease observed in histamine-induced bronchoconstriction is mainly due to reflex effects evoked by stretch receptor stimulation.

Animals↗

Fentanyl-induced airway hyperreactivity in the guinea pig.

The bronchopulmonary effects of fentanyl were studied in mechanically ventilated, paralyzed guinea pigs that had been anaesthetized with pentobarbitone sodium. Fentanyl did not alter the resting bronchial tone but enhanced the bronchoconstrictor effects of 5-hydroxytryptamine in a dose-related manner. The enhancement induced by 20 micrograms kg-1 fentanyl was suppressed by pretreatments with 0.5 mg kg-1 naloxone or 5 mg kg-1 propranolol, but did not change after 3 mg kg-1 atropine. The bronchoconstrictor responses to histamine were also enhanced by 20 micrograms kg-1 fentanyl. These results suggest that fentanyl-induced airway hyperreactivity is not mediated by an increase in vagal tone but is due to a reduction in the central sympathetic drive and/or in the levels of circulating catecholamines, which occurs through stimulation of opiate receptors.

Animals↗

Effects of propranolol on pulmonary gas exchange in patients with cirrhosis.

Propranolol, a beta-blocking agent, has been proposed in the prevention of gastro-intestinal bleeding in cirrhotic patients, and is known for its bronchoconstrictive effects. Since hypoxemia is a frequent finding in patients with cirrhosis, this work was undertaken to study the effects of intravenous propranolol on pulmonary function and on gas exchange in these patients. The 10 patients studied had cirrhosis associated with an increase in the alveolar arterial O2 difference, (A-a)DO2, an index of arterial oxygenation impairment. Their 1-s forced expiratory volume/forced vital capacity (FEV1/FVC) was normal, but in most a reduction of the forced expiratory flow of 25-75% of vital capacity was observed (FEF 25-75), suggestive of some degree of small airway obstruction. Although propranolol induced a significant decrease of FEF 25-75 from 67.7 +/- 19.3% to 55.4 +/- 21.5% (P less than 0.01), suggesting a bronchoconstriction of the small airways, there was no significant decrease in mean arterial oxygen partial pressure (PaO2) (74.1 +/- 6.4 mmHg before and 77.0 +/- 6.5 mmHg after propranolol). Indeed, a slight but significant improvement of the (A-a)DO2 was observed, from 39.1 +/- 5.9 mmHg to 34.4 +/- 4.9 mmHg (P less than 0.02). Although the mechanism of this beneficial effect remains to be elucidated, we conclude that in spite of its bronchoconstrictive action, propranolol is not contra-indicated in cirrhotic patients with hypoxemia who have normal expiratory flow.

Adult↗

Increase in tracheal pressure during jet ventilation.

Gas injection systems used in several techniques of ventilation cause increases in airway pressure and physiological changes which are frequently overlooked. The momentum flux theory describes such phenomena most appropriately. We have defined and measured the characteristics of such increases in airway pressure, using a lateral tracheal injection system which has been described previously. In such a system, wall friction is a major source of loss in jet momentum flux, in contrast with the changes in axis-symmetrical systems. This process results in a potentially beneficial increase in airway pressure and in greater mixing, which might be clinically useful.

Animals↗

Influence of body temperature on histamine-induced bronchoconstriction in guinea pigs.

The effects of body temperature on histamine-induced bronchoconstriction were investigated in anesthetized, paralyzed, and mechanically ventilated guinea pigs. Four groups of guinea pigs were studied with constant body temperatures of 40, 38, 35, and 32 degrees C, respectively. Histamine was infused for 5 min at a rate of 50 ng.kg-1.s-1. Body cooling from 40 to 32 degrees C augmented the bronchomotor responses to histamine, which eventually rose almost fourfold. The enhancement of histamine-induced bronchoconstriction induced by body cooling was not suppressed by pretreating guinea pigs with 5 mg/kg hexamethonium or 5 mg/kg hexamethonium plus 3 mg/kg atropine; neither was the enhancement of histamine-induced bronchoconstriction suppressed in pithed guinea pigs, demonstrating that the autonomic nervous system is not involved in potentiating bronchoconstriction at low body temperatures. These results suggest that, at low body temperatures, increased airway responsiveness to histamine may be because of some direct effect of temperature on bronchial airway smooth muscle.

Animals↗

Cholinergic component of histamine-induced bronchoconstriction in newborn guinea pigs.

The magnitude of parasympathetic reflex-mediated bronchoconstriction during histamine infusion was compared in anesthetized paralyzed newborn and adult guinea pigs. The animals were ventilated using a constant-flow ventilator, and the conductance and compliance of the respiratory system were continuously monitored. We found that reactivity to histamine infusion was less in newborns than in adults, because newborns required a larger dose of histamine than adults (300 vs. 125 ng.kg-1.s-1) to produce an equivalent decrease in conductance (42 +/- 13 vs. 42 +/- 15%). Vagal interruption by bilateral cervical vagotomy or muscarinic blockade with atropine (3 mg/kg) significantly reduced the bronchoconstrictor response to histamine in adults. By contrast, neither vagotomy nor atropine significantly changed this response in the newborns. These results indicate the lack of a vagal component in the bronchoconstriction that histamine induced in the newborns. Their relative unresponsiveness to histamine might partly be related to the fact that, in the newborn, histamine mainly acts directly via its airway receptors.

Aging↗

Effect of air entrainment on airway pressure during endotracheal gas injection.

Turbulent jets in endotracheal tubes induce air entrainment and airway pressure changes. We attempted to understand the physical explanation for these effects, which open up to a wide range of applications in intubated patients. An in vitro study was performed on standard size endotracheal tubes with diameters of 8, 7, and 3 mm and several capillaries molded into the wall (less than 1 mm diam) allowing gas injection at approximately 1-2 cm from the tracheal end of the endotracheal tube. This produced a jet velocity-dependent gain in tracheal pressure (Ptr) during inspiration. Data have been interpreted with a theory, based on the classic momentum theorem, which indicates that the mechanisms involved resemble those of axisymmetrical confined jets: air entrainment by turbulent friction with a longitudinal increase in lateral pressure. The difference with axisymmetrical systems lies in the nonconservation of the total thrust in our system because, secondary to wall friction and to the nonaxial incidence of the jets, only a fraction of the jet momentum flux is transformed into pressure. This suggests faster mixing in the present lateral jet system, as shown by 1) the independence of Ptr on tracheal geometry and 2) the very rapid increase in lateral pressure. The present study supports the idea that pressure changes in the airways, which are potentially beneficial in intubated patients, can be satisfactorily generated by turbulent jets.

Intubation, Intratracheal↗

Nonadrenergic bronchodilation in adult and young guinea pigs.

The contribution of the nonadrenergic inhibitory system to airway responses to infusion of 5-hydroxytryptamine (5-HT) was evaluated in anesthetized, tracheotomized, and paralyzed young (13 days) and adult (82 days) guinea pigs. Animals were mechanically ventilated by a constant flow ventilator. Compliance (C) and conductance (G) of the respiratory system were continuously monitored. Three series of experiments were performed involving intravenous pretreatment with 1) atropine (3 mg/kg) and propranolol (1 mg/kg); 2) atropine (3 mg/kg), propranolol (1 mg/kg), and phentolamine (2 mg/kg); and 3) atropine (3 mg/kg) and hexamethonium (2 mg/kg). 5-HT was then intravenously infused for 5 min at a rate of 40 ng.kg-1.s-1 in adults and 60 ng.kg-1.s-1 in young guinea pigs to obtain the same degree of bronchoconstriction in both groups. At the 3rd min of the infusion, bilateral cervical vagotomy was performed and C and G were measured at the maximal response, 1-2 min thereafter. Vagotomy increased bronchoconstriction (P less than 0.01) in both young animals and adults. Phentolamine did not modify this increase, but hexamethonium completely inhibited it. These results indicate that, in adult and young guinea pigs, 5-HT infusion induces reflex activation of the nonadrenergic inhibitory system, which in turn modulates the bronchoconstrictor responses to 5-HT. This neural modulation is not mediated by an alpha-adrenergic pathway.

Animals↗

Inspiratory pressure support prevents diaphragmatic fatigue during weaning from mechanical ventilation.

Persistent inability to tolerate discontinuation from mechanical ventilation is frequently encountered in patients recovering from acute respiratory failure. We studied the ability of inspiratory pressure support, a new mode of ventilatory assistance, to promote a nonfatiguing respiratory muscle activity in eight patients unsuccessful at weaning from mechanical ventilation. During spontaneous breathing, seven of the eight patients demonstrated electromyographic signs of incipient diaphragmatic fatigue. During ventilation with pressure support at increasing levels, the work of breathing gradually decreased (p less than 0.02) as well as the oxygen consumption of the respiratory muscles (p less than 0.01), and electrical signs suggestive of diaphragmatic fatigue were no longer present. In addition, intrinsic positive end-expiratory pressure was progressively reduced. For each patient an optimal level of pressure support was found (as much as 20 cm H2O), identified as the lowest level maintaining diaphragmatic activity without fatigue. Above this level, diaphragmatic activity was further reduced and untoward effects such as hyperinflation and apnea occurred. When electrical diaphragmatic fatigue occurred, the activity of the sternocleidomastoid muscle was markedly increased, whereas it was minimal when the optimal level was reached. We conclude that in patients demonstrating difficulties in weaning from the ventilator: (1) pressure support ventilation can assist spontaneous breathing and avoid diaphragmatic fatigue (pressure support allows adjustment of the work of each breath to provide an optimal muscle load); (2) clinical monitoring of sternocleidomastoid muscle activity allows the required level of pressure support to be determined to prevent fatigue.

Acute Disease↗

Mechanisms of endothelin-mediated bronchoconstriction in the guinea pig.

Intravenous injection of anesthetized ventilated guinea pigs with doses of endothelin ranging from 0.25 to 2.50 micrograms/kg caused dose-dependent decreases in respiratory system conductance and compliance. These effects were maximal 1 min after injection and had disappeared 15 min thereafter. When guinea pigs were pretreated with 3 mg/kg of propranolol or 5 mg/kg of hexamethonium, endothelin-induced bronchoconstriction rose significantly, but when they were pretreated with 3 mg/kg of propranolol plus 3 mg/kg of atropine it remained unchanged. The bronchoconstrictor effects of endothelin were suppressed in guinea pigs pretreated with 0.5 or 2 mg/kg of meclofenamate but remained unchanged in those pretreated with 30 micrograms/kg of nicardipine. Endothelin did not increase either lung permeability, as assessed by 99m technetium diethylenetriamine pentaacetic acid clearance, or airway responsiveness to histamine or 5-hydroxy-tryptamine. Histological studies showed that endothelin induced reversible contraction of airway and pulmonary artery smooth muscles but no inflammatory reactions. These results demonstrate that, in guinea pigs, endothelin 1) induces airway smooth muscle contraction mediated by cyclooxygenase metabolites and modulated by the autonomic nervous system and 2) does not induce airway hyperreactivity or inflammation.

Animals↗

Comparison of the constant flow and occlusion methods for assessment of bronchoconstriction in guinea-pigs.

Assessments of total respiratory compliance (C) and conductance (G) with the constant inspiratory flow and the occlusion methods were compared in the basal state and during histamine or serotonin induced bronchoconstriction in 22 normal, anaesthetized, paralysed, mechanically ventilated guinea-pigs. In the basal state, no significant difference was found between the C and G values measured by both methods. During drug-induced bronchoconstriction, small but significant differences were observed between the respiratory parameters measured by the two methods, and expressed as the percentage ratio (R) to the corresponding basal values (respectively RCCF and RCOC, and RGCF and RGOC). This discrepancy, which was independent of the drug and of the dose, was probably attributable to a modification of the visco elastic properties of the lung due to either the mechanical ventilation or the infused drug. Nevertheless, this study demonstrates that both methods can be considered as equivalent for bronchoconstriction assessment because very strong correlations were found between RCCF and RCOC (r = 0.96, p less than 0.001) and between RGCF and RGOC (r = 0.97, p less than 0.001), and because the slopes of the linear relationships were not significantly different from unity in both cases.

Animals↗

Four and six parameter models of forced random noise respiratory impedance in normals.

Total respiratory impedance has been measured between 3-42 Hz by the forced random noise technique, in 15 subjects breathing either air or a helium oxygen mixture in three experimental conditions: at basal state, and then with a resistor or a tube added at the mouth. Impedance is modelled, either by a 4-parameter model (M4), derived from the series model (resistance, inertance, compliance) by making resistance a linear function of frequency; or by a 6-parameter model (M6) including a central compartment (airway resistance and gas inertance), and a tissue compartment (resistance, inertance and compliance in series) placed in parallel with alveolar gas compliance. The additive resistance is perfectly evaluated by both models, whereas the additive inertance is not accurately estimated by the model M6, the fitting of which combines the real and imaginary parts of impedance. Resistance extrapolated at zero frequency on the one hand, inertance of M4 and central inertance of M6 of the other, are highly correlated. However, changes in some parameters of both models according to the experimental conditions are difficult to explain on physiological grounds. We conclude that the model M6 cannot be easily and accurately identified over such a limited frequency range, at least in normals, while the model M4 yields a simplified description of impedance which may be sufficient for diagnostic purposes.

Airway Resistance↗

Risk factors of postoperative pulmonary complications after vascular surgery.

Smoking and chronic obstructive disease are common in patients who undergo vascular surgery. These patients seem especially at risk for postoperative respiratory complications (PRCs). The value of preoperative spirometric tests to determine the risk of PRC has been recently challenged. The current prospective study was undertaken to identify the risk factors of PRC in these patients. One hundred fifty-one patients, including 67 patients who underwent abdominal aortic surgery, were included in this study. Preoperative and peroperative parameters were collected and analyzed in a multivariate analysis. PRCs were classified as minor and major. A significantly prolonged postoperative hospital stay was associated with major complications (21.3 +/- 9.0 vs 14.3 +/- 6.0 days). The overall incidence of PRC was 37.1%, and the incidence of major PRC was 15.2%. Patients who underwent abdominal aortic surgery had a higher incidence of PRC (53%; major PRC, 24%). In addition to abdominal aortic surgery, other risk factors were chest deformation, recent bronchitis, duration of surgery, and FEV1/VC. In patients who underwent abdominal aortic surgery, the risk factors for major PRC were decreases in preoperative FEV1/VC and PaO2. This study confirms the importance of an evaluation of a patient's respiratory condition, especially by preoperative spirometry and blood gas analysis, to determine the risk of PRC in a given population. General risk factors, such as the American Society of Anesthesiologists' classification, fail to achieve this task. The identification of patients with unacceptable risks remains a challenge.

Aorta, Abdominal↗

Effects of rilmenidine on bronchomotor responses in the guinea pig.

This study compares the effects of 2 alpha 2-adrenergic agonists, rilmenidine (S 3341) and clonidine, on histamine-induced bronchoconstriction (HIB) in guinea pigs. Clonidine has previously been shown to potentiate HIB in guinea pigs. The study was conducted in anesthetized, paralyzed and ventilated guinea pigs. Six groups of at least 6 guinea pigs were pretreated with saline, rilmenidine (0.1, 0.3 and 1 mg/kg intravenously) or clonidine (0.01 and 0.03 mg/kg intravenously), respectively. Conductance, dynamic compliance and static compliance of the respiratory system were measured before and during histamine infusion (80 ng/kg/s) and expressed as percent variation. Clonidine potentiated HIB as previously reported. In contrast, rilmenidine potentiated HIB only at the dose of 1 mg/kg. As it is well known that HIB is influenced by adrenergic outflow, these results suggest that rilmenidine has less inhibitory effect than clonidine on adrenal secretion.

Adrenergic alpha-Agonists↗

Respiratory mechanics for assessment of histamine bronchopulmonary reactivity in guinea pigs.

In the course of bronchial challenge, bronchopulmonary response assessment requires pleural pressure measurement. This measurement, mostly obtained in guinea pigs by a pleural catheter, is difficult to perform in anaesthetized paralysed ventilated animals needing periodical large inflations. The aim of this study was to demonstrate that the pulmonary response to intravenous histamine can be correctly appreciated from the respiratory response. In twelve anaesthetized paralysed mechanically ventilated guinea pigs, pulmonary and respiratory compliances (CL and Crs), were measured together with pulmonary and respiratory conductances (GL and Grs), using the method proposed by Rossi et al. (J. Appl. Physiol. 58: 1849-1858, 1985). Pulmonary and total respiratory mechanics were compared in the basal state, and at the end of a 5 min histamine infusion (100 ng.kg-1.sec-1). Pulmonary and respiratory compliances under histamine (HCL and HCrs), as well as pulmonary and respiratory conductances under histamine (HGL and HGrs), were expressed as a percentage of the corresponding basal values. Highly significant correlations were found between HCL and HCrs on the one hand (r = 0.98, P less than 0.001), and HGL and HGrs on the other (r = 0.97, P less than 0.001). We conclude that, in guinea pigs, the response of the total respiratory system to histamine infusion provides a simple and accurate assessment of the pulmonary response.

Animals↗