Mechanisms of capsaicin- and lactic acid-induced bronchoconstriction in the newborn dog.
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1. Capsaicin activation of the pulmonary C fibre vanilloid receptor (VR1) evokes the pulmonary chemoreflex and reflex bronchoconstriction. Among potential endogenous ligands of C fibre afferents, lactic acid has been suggested as a promising candidate. We tested the hypotheses that (a) lactic acid behaves as a stimulant of C fibre receptors in the newborn dog to cause reflex bronchoconstriction, and (b) lactic acid causes reflex bronchoconstriction via the same pulmonary C fibre receptor mechanism as capsaicin using the competitive capsaicin/VR1 receptor antagonist capsazepine. 2. Right heart injection of lactic acid caused a significant increase (47 +/- 8.0 %) in lung resistance (RL) that was atropine sensitive (reduced by 75 %; P < 0.05), consistent with reflex activation of muscarinic efferents by stimulation of C fibre afferents. 3. Infusion of the competitive capsaicin antagonist capsazepine caused an 80 % reduction (P < 0.01) in the control bronchoconstrictor response (41 +/- 8.5 % increase in RL) to right heart injections of capsaicin. The effects of capsazepine are consistent with reversible blockade of the VR1 receptor to abolish C fibre-mediated reflex bronchoconstriction. 4. Lactic acid-evoked increases in RL were unaffected by VR1 blockade with capsazepine, consistent with a separate lactic acid-induced reflex mechanism. 5. We conclude that (a) putative stimulation of C fibres with lactic acid causes reflex bronchoconstriction in the newborn dog, (b) capsazepine reversibly antagonizes reflex bronchoconstriction elicited by right heart injection of capsaicin, presumably by attenuating capsaicin-induced activation of the C fibre 'capsaicin' receptor (VR1), and (c) capsazepine resistance of lactic acid-induced bronchoconstriction indicates that lactic acid evokes reflex bronchoconstriction by a separate mechanism, possibly via the acid-sensing ionic channel. (+info)
Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide modulation.
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Bradykinin has an important role in asthma pathogenesis, but its site of action is unclear. It was previously reported by the authors that bradykinin causes a dose-dependent reduction in dynamic compliance but little change in total lung resistance. This suggested that bradykinin may have a preferential effect in the distant lung. The purpose of the current investigation was to better characterize the effects of bradykinin on pulmonary resistance in rodents and explore the role of nitric oxide release in modulating the effect of bradykinin. Airway constriction was induced in the rats by aerosol administration of bradykinin with or without treatments with the inhaled bradykinin-2 receptor antagonist, Hoe 140 or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester or N(G)-monomethyl-L-arginine. Total lung resistance was partitioned into tissue and airway resistance by using the alveolar capsule method. Bradykinin induced a significant increase in both resistances. Hoe 140 abolished the response to bradykinin. The nitric oxide synthase inhibitors enhanced the bronchoconstricting response. In conclusion, the bradykinin response in the rats was not only localized to conducting airways but also involved a relatively selective tissue reaction. Bradykinin-induced bronchospasm in the rat is solely due to activation of bradykinin-2 receptor. Further, it was shown that nitric oxide significantly modulates the bronchospasm caused by bradykinin, suggesting that nitric oxide is an important modulator of airways responsiveness to bradykinin. (+info)
Compliance and stability of the bronchial wall in a model of allergen-induced lung inflammation.
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Airway wall remodeling in response to inflammation might alter load on airway smooth muscle and/or change airway wall stability. We therefore determined airway wall compliance and closing pressures in an animal model. Weanling pigs were sensitized to ovalbumin (OVA; ip and sc, n = 6) and were subsequently challenged three times with OVA aerosol. Control pigs received 0.9% NaCl (n = 4) in place of OVA aerosol. Bronchoconstriction in vivo was assessed from lung resistance and dynamic compliance. Semistatic airway compliance was recorded ex vivo in isolated segments of bronchus, after the final OVA aerosol or 0.9% NaCl challenge. Internally or externally applied pressure needed to close bronchial segments was determined in the absence or presence of carbachol (1 microM). Sensitized pig lungs exhibited immediate bronchoconstriction to OVA aerosol and also peribronchial accumulations of monocytes and granulocytes. Compliance was reduced in sensitized bronchi in vitro (P < 0.01), and closing pressures were increased (P < 0.05). In the presence of carbachol, closing pressures of control and sensitized bronchi were not different. We conclude that sensitization and/or inflammation increases airway load and airway stability. (+info)
Physiologic basis and interpretation of common indices of respiratory mechanical function.
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Tests of pulmonary mechanical function may be used in determining the prominent site of pulmonary reaction to intervention. Responses may be localized from a knowledge of changes in lung resistance and compliance. A peripheral airway or parenchymal response is characterized by a decrease in lung compliance. A central airway reaction is characterized by an increase in pulmonary resistance. In mixed reactions both parameters may change. In this communication some of the physiologic determinants of pulmonary resistance and compliance are discussed and examples of localized responses given. (+info)
The immediate effect of a Boston brace on lung volumes and pulmonary compliance in mild adolescent idiopathic scoliosis.
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Idiopathic scoliosis (IS) is known to result in lung volume and pulmonary compliance reduction. Boston brace treatment of IS is an additional factor causing restrictive respiratory syndrome due to external chest wall compression. Nevertheless, the immediate effect of Boston bracing on the pulmonary compliance of scoliotic patients has not been studied systematically. Spirometric and plethysmographic lung volumes, static lung compliance (C(ST)(L)) and specific lung compliance (C(ST)(L)/functional residual capacity) of 15 scoliotic adolescents (14 females and 1 male, of mean age 14.1+/-1.67 years, with mean Cobb angle 24.1 degrees+/-7.88 degrees) were recorded twice, in a random sequence: once without the Boston brace (nBB) and once immediately after wearing the brace (BB). Our findings showed that bracing reduced vital capacity, residual volume, functional residual capacity (FRC), total lung capacity, and forced expiratory volume in 1s in a proportional and significant way (P < 0.001). C(ST)(L) was also significantly reduced (P < 0.001), but C(ST)(L)/FRC remained unaltered. All BB and nBB indices were highly correlated. We concluded that Boston bracing in IS patients results in an immediate, predictable, and uniform reduction of lung volumes and pulmonary compliance. The reduction of C(ST)(L) under bracing conditions was related to the decrease of lung volume; the C(ST)(L)/FRC remained unaltered. (+info)
Randomised controlled trial of effect of terbutaline before elective caesarean section on postnatal respiration and glucose homeostasis.
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AIM: To determine if terbutaline given to mothers before elective caesarean section facilitates neonatal respiration and metabolism. METHODS: A randomised controlled trial of 25 full term infants delivered by elective caesarean section was conducted. The mothers received a continuous infusion of terbutaline or saline 120-0 minutes before birth. Umbilical artery blood was collected at birth and analysed for blood gases and catecholamines. The lung function of each infant was assessed two hours after birth, and blood pressure, heart rate, blood glucose and body temperature were monitored until 24 hours of age. RESULTS: The infants of the treated mothers (n = 13) had significantly higher dynamic lung compliance (p < 0.001), lower airway resistance (p < 0.001), and respiratory frequency than control infants (n = 12). Blood glucose and adrenaline concentrations were significantly higher in the treated group (p = 0.0014 and p < 0.01). None of these infants had any clinical respiratory difficulties; there were two cases of transient tachypnoea in the control group. No negative side effects due to the terbutaline treatment were seen among the infants. The mothers felt no discomfort caused by the terbutaline infusion, although they bled more during surgery (p = 0.03). CONCLUSION: Stimulation of the beta adrenoceptors in utero with terbutaline infusion to the mothers promotes neonatal respiratory and metabolic adaptation after elective caesarean section. (+info)
Effects of smoking in pregnancy on neonatal lung function.
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AIMS: To assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking. METHODS: Lung function tests were carried out within 72 hours of delivery in infants born to 100 non-smoking and 189 smoking mothers. Lung growth was assessed by plethysmography and lung mechanics using the single breath occlusion technique and oesophageal balloon/pneumotachography. Antenatal maternal serum cotinine values were obtained from 133 mothers. RESULTS: Smoking was associated with a significant reduction in birthweight (mean 256 g, 95% CI 0.164 to 0.392), and length (mean 1.26 cm, 95% CI 0.48 to 2.00). Lung volume was not reduced when related to weight. Smoking was associated with a highly significant reduction in static compliance (Crs). This effect remained significant after relating Crs to weight and lung volume. Regression analyses showed that the Crs association was limited to the boys. Smoking was associated with a small but significant reduction in respiratory system conductance (Grs) (single breath occlusion technique) and total pulmonary conductance (Gp). These associations were limited to girls. CONCLUSIONS: Smoking in pregnancy reduces static compliance in boys and conductance in girls. There was no evidence that maternal smoking adversely affected fetal lung growth. (+info)
'Alveolar recruitment strategy' improves arterial oxygenation during general anaesthesia.
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Abnormalities in gas exchange during general anaesthesia are caused partly by atelectasis. Inspiratory pressures of approximately 40 cm H2O are required to fully re-expand healthy but collapsed alveoli. However, without PEEP these re-expanded alveoli tend to collapse again. We hypothesized that an initial increase in pressure would open collapsed alveoli; if this inspiratory recruitment is combined with sufficient end-expiratory pressure, alveoli will remain open during general anaesthesia. We tested the effect of an 'alveolar recruitment strategy' on arterial oxygenation and lung mechanics in a prospective, controlled study of 30 ASA II or III patients aged more than 60 yr allocated to one of three groups. Group ZEEP received no PEEP. The second group received an initial control period without PEEP, and then PEEP 5 cm H2O was applied. The third group received an increase in PEEP and tidal volumes until a PEEP of 15 cm H2O and a tidal volume of 18 ml kg-1 or a peak inspiratory pressure of 40 cm H2O was reached. PEEP 5 cm H2O was then maintained. There was a significant increase in median PaO2 values obtained at baseline (20.4 kPa) and those obtained after the recruitment manoeuvre (24.4 kPa) at 40 min. This latter value was also significantly higher than PaO2 measured in the PEEP (16.2 kPa) and ZEEP (18.7 kPa) groups. Application of PEEP also had a significant effect on oxygenation; no such intra-group difference was observed in the ZEEP group. No complications occurred. We conclude that during general anaesthesia, the alveolar recruitment strategy was an efficient way to improve arterial oxygenation. (+info)