Exercise-induced Bronchodilation Equalizes Exercise Ventilatory Mechanics despite Variable Baseline Airway Function in Asthma.

PURPOSE: We quantified the magnitude of exercise-induced bronchodilation in adult asthmatics under conditions of narrowed and dilated airways. We then assessed the effect of the bronchodilation on ventilatory capacity and the extent of ventilatory limitation during exercise. METHODS: Eleven asthmatics completed three exercise bouts on a cycle ergometer. Exercise was preceded by no treatment (trialCON), inhaled ß2 agonist (trialBD), or a eucapnic voluntary hyperpnea challenge (trialBC). Maximal expiratory flow-volume maneuvers (MEFV) were performed before and within 40 s of exercise cessation. Exercise tidal flow-volume loops were placed within the preexercise and postexercise MEFV curve and used to determine expiratory flow limitation and maximum ventilatory capacity (V˙ECap). RESULTS: Preexercise airway function was different among the trials (forced expiratory volume 1 s during trialCON, trialBD, and trialBC = 3.3 ± 0.8 L, 3.8 ± 0.8 L, and 2.9 ± 0.8 L, respectively; P < 0.05). Maximal expired airflow increased with exercise during all three trials, but the increase was greatest during trialBC (delta forced expiratory volume 1 s during trialCON, trialBD, and trialBC = +12.2% ± 13.1%, +5.2% ± 5.7%, +28.1% ± 15.7%). Thus, the extent of expiratory flow limitation decreased, and V˙ECap increased, when the postexercise MEFV curve was used. During trialCON and trialBC, actual exercise ventilation exceeded V˙ECap calculated with the preexercise MEFV curve in seven and nine subjects, respectively. CONCLUSIONS: These findings demonstrate the critical importance of exercise bronchodilation in the asthmatic with narrowed airways. Of clinical relevance, the results also highlight the importance of assessing airway function during or immediately after exercise in asthmatic persons; otherwise, mechanical limitations to exercise ventilation will be overestimated.

Hepatopulmonary syndrome has low prevalence of pulmonary vascular abnormalities on chest computed tomography.

PURPOSE: Hepatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatations associated with hepatic disease. This study aimed to assess the prevalence of type 1 and 2 pulmonary vascular abnormalities on chest computed tomography (CT) in patients with cirrhosis and HPS and to characterize intra- and interobserver reliability. MATERIALS AND METHODS: Two thoracic radiologists retrospectively evaluated chest CT scans from 38 cirrhosis patients with HPS. They classified the pulmonary vascular abnormalities as type 1 (multiple dilated distal pulmonary arteries), type 2(nodular dilatation or individual pulmonary arterial malformation), or absence of abnormality. Furthermore, they measured the diameters of the central pulmonary arteries and subsegmental pulmonary arteries and bronchi. We analyzed the prevalence, intraobserver reliability, and interobserver reliability of abnormal CT findings related to HPS, and the correlation of these findings with partial arterial oxygen pressure (PaO2). RESULTS: The overall prevalence of pulmonary vascular abnormalities was 28.9% (95% confidence intervals: 15.4%, 45.9%). Moreover, 26.3% of patients had type 1 abnormality (13.4%, 43.1%) and 2.6% of patients had type 2 abnormality (0.0%, 13.8%). The intraobserver reliability kappa value was 0.666 (0.40, 0.91) and the interobserver kappa value was 0.443 (0.12, 0.77). There was no correlation between pulmonary vascular abnormalities on CT and PaO2 values. CONCLUSIONS: The prevalence of pulmonary vascular abnormalities on chest CT of patients with cirrhosis and HPS is low and not correlated with PaO2. These findings question the usefulness of chest CT for the evaluation of patients with cirrhosis and HPS.

Evaluación funcional de la vía aérea / Functional asessment of airway

Airway function study includes a variety of tests involving various sub-specialties of medicine and related professions. We describe the methods that assess: 1) upper airway (nose to larynx): rhinomanometry, acoustic rhinometry and nasopharingolaryngoscopy, 2) central airways (trachea and main bronchi): bronchoscopy, imaging study and Flow / Volume curve, 3) distal or peripheral airway: spirometry, bronchodilator response assessment, airway hyper responsiveness and measurement of airway resistance (plethysmography, interrupted resistence and impulse oscillometry).

El estudio de la función de la vía aérea abarca una gran variedad de exámenes que implican a diversas subespecialidades de la medicina y profesiones relacionadas. Se describen los métodos que evalúan: 1) vía aérea superior (nariz hasta laringe): rinomanometría, rinometría acústica y nasofarigolaringoscopía, 2) vía aérea central (tráquea y bronquios mayores): bronconcoscopia, estudio de imágenes y curva flujo/volumen, 3) vía aérea distalo periférica: espirometría, evaluación de respuesta a broncodilatador y de hiperreactividad bronquial y medición de la resistencia de la vía aérea (pletismografía, resistencia interrumpida y oscilometría de impulso).

The proximal airway of the bat Tadarida brasiliensis: a minimum entropy production design.

The bronchial tree of most mammalian lungs is a good example of an efficient distribution system whose geometry and dimensions of branched structures are important factors in determining the efficiency of respiration. Small and flying endothermic animals have high-energy requirements, requiring morphological and physiological adaptations to reduce energy loss. Here we show that Tadarida brasiliensis, a nocturnal small bat whose energy requirements are exacerbated by this small size and by their frequent exposure to high altitude, has a different morphology in the proximal airway, sustained by a wider trachea and better scaling factors, than other non-flying mammals. This design allows a great decrease of the volume specific resistance of the proximal airway and in consequence a very low entropy production during breathing, approximately 1/18 of that expected for a non-flying mammals of similar body size.

Immune cell infiltration and broncovascular remodeling after nitric acid nasal instillation in a mouse bronchiolitis obliterans model.

Immune cell airway infiltration and the bronchovascular remodeling process have shown to be promising in the understanding of bronchiolitis obliterans (BO) pathogenesis. In this study we sought to validate the importance of immune cells, whether diffusely distributed or forming lymphoid follicles, collagen density, and vascular factors. Eight weeks after a single nitric acid (NA) nasal instillation, lung changes were characterized by lumen distortion, epithelial layer folding, reduction or total obliteration of terminal bronchiole (TB) lumen, and wall thickness increase. The morphologic changes in the TB and TA (terminal artery) lumen coincide with the measurement difference in the three groups. The TB diameter and lumen were significantly decreased in BO when compared with non-BO lungs (0.76 +/- 0.05 microm vs. 0.81 +/- 0.05 microm and 12,286.13 +/- 378.83 microm vs. 18,182.27 +/- 5,593.98 microm, p = 0.05 and p = 0.01, respectively). Equally significant was the increase in TB thickness in BO when compared with the non-BO group (201.72 +/- 35.75 microm vs. 149.75 +/- 40.61 microm, p = 0.007). The morphologic changes in immune cells seen in TB, TA, and bronchus-associated lymphoid tissue (BALT) also coincide with the quantification differences observed in the three groups. We concluded that immune cell infiltration and collagen/vascular remodeling are related to the spectrum of histologic changes in a BO nasal-induced model in mice and may be an appropriate target for prospective studies of human bronchiolitis.

Estimation of tube wall compliance using pulse-echo acoustic reflectometry.

This paper focuses on the estimation of tube wall compliance using reflection analysis of acoustic pulses. The wall compliance of a rubber latex tube was found theoretically using an acoustical transmission line model. Wall compliance was also obtained experimentally from acoustical and mechanical measurements. The acoustically estimated, mechanically estimated, and simulated wall compliances were CwEXP=6.55x10(-7) cm5/dyne, CwMech=6.89x10(-7) cm5/dyne and CwSim=5.18x10(-7) cm5/dyne respectively. The methods developed and the preliminary results obtained from this research could serve as the groundwork for the development of a device that determines the pathological condition of compliant biological conduits such as the airways.

Dopaminergic modulation of human bronchial tone.

BACKGROUND: Dopamine exerts inhibitory and excitatory effects on different systems. Its effect on human bronchial tone is controversial. It has been reported that dopamine has no acute effect on human airways from normal subjects or those with asthma background. However, inhaled or infused dopamine decreased histamine-induced bronchoconstriction in both normal and asthmatic subjects. METHODS: We examined the possible modulating effect of dopamine on bronchial diameter by administering inhaled dopamine and the DA(2) dopaminergic blocker metoclopramide (MTC) to subjects with various degrees of bronchial tone. We examined 50 volunteers. Arterial blood pressure and heart rate were determined in each subject. By means of spirometry, we measured forced vital capacity (FVC), forced expiratory volume in the first second (FEV(1)), maximal forced expiratory flow (FEF(max)), and forced expiratory flow at 50% of vital capacity (FEF(50)), before and after each treatment. By inhalation with a nebulizer, we administered the following: a) dopamine (0.5 microg/kg/min) to 10 healthy subjects, 10 subjects with asthma without acute bronchospasm (AWAB), and nine subjects with acute asthma attack (AAA), and b) intravenous (i.v.) metoclopramide (7 microg/kg/min) was administered to 10 healthy subjects and 11 subjects with AWAB. For ethical reasons, MTC was not used in subjects with acute asthma attack. Non-parametric Wilcoxon test for paired samples, ANOVA test, and Bonferroni multiple comparison test were performed. Inhaled dopamine increased FEV(1) and FVC, FEF(max), and FEF(50) in the AAA group, but there were no modifications in the healthy group or in the AWAB group. Metoclopramide did not induce changes in respiratory parameters in healthy individuals or in those with AWAB. CONCLUSIONS: Inhaled dopamine is able to induce bronchodilatation when the bronchial tone is already increased by acute asthma attack but did not modify the resting bronchial tone in normal subjects or in asthmatics without acute bronchospasm. Additionally, DA(2) blockade with metoclopramide did not modify resting bronchial tone. Dopamine exerts a modulatory effect on the bronchial tone of human airways depending on the degree of preexisting tone.

The perfused guinea-pig lung revisited: a study of EDRF-no system.

Adult male guinea pigs from both sexes were anaesthetized with pentobarbital (40mg/Kg). After tracheotomy the lungs were perfused with Krebs-Henseleit solution at 37 degrees C in a non recirculated system composed of a perfusion pump, a transducer to measure pressure and another one to measure bronchial resistance. In all groups studied histamine injections were made at the doses of 50, 100, 200 and 400 microg/ml as a bolus. Propranolol (1 microg/ml) added to the perfusate, promoted a remarkable increase in perfusion pressure (p<0.001) and a significant augmentation in bronchoconstriction (p<0.05). When indometacin (10 microg/ml) was added to the perfusate, a great increase in histamine induced bronchoconstriction was observed, that was followed by a remarkable increase in perfusion pressure. Methylene blue at the dose of 8.25 microg/ml increased bronchorreativity as well as the perfusion pressure significantly. L-arginine (3.5 microg/ml) added to the perfusate, did not promote reactivity. The addition of L-arginine plus NADPH (1 microg/ml), promoted a significant decrease in bronchoconstriction (p<0.01). In both cases, perfusion pressure increased when compared to controls. Nitroarginine (2.5 microg/ml) greatly increased perfusion pressure with no change in bronchoconstriction. Therefore, we conclude that nitric oxide (NO) is a very important modulator for keeping the low perfusion pressure and bronchodilation of the isolated perfused guinea pig lung.

Ontogenetic changes in the fractal geometry of the bronchial tree in Rattus norvegicus.

Respiration and metabolism change dramatically over the course of the development of vertebrates. In mammals these changes may be ascribed to organogenesis and differentiation of structures involved in gas exchange and transport and the increase in size. Since young as well as mature individuals must be well-designed if the species is to survive, the physiological changes during the development should be matched with geometrical or structural adjustments of the respiratory system. The aim of this study was to evaluate changes in the fractal geometry of the bronchial tree during the postnatal development of the rat. The average fractal dimension of the bronchial tree of the rats was 1.587, but that of juveniles was larger than that of the adults. We found a significant negative correlation between age and fractal dimension. This correlation could be considered be misleading because of the difficulty of separating age/body size effects. Nevertheless, because fractal dimensions of the bronchial tree of rabbits and humans are known to be similar, 1.58 and 1.57 respectively, the body size effect may be nil. To our knowledge, this is the first report of ontogenetic changes in the fractal dimension of the bronchial tree in mammals.

Contribution of nitric oxide, prostanoids and Ca(2+)-activated K+ channels to the relaxant response of bradykinin in the guinea pig bronchus in vitro.

In the guinea pig bronchus with epithelium, pre-contracted with histamine, bradykinin (BK), lysyl-BK, prostaglandin E2 (PGE2), cromakalim and S-nitroso-N-acetylpenicillamine each caused graded relaxation with mean EC50s of 34 nM, 11 nM, 0.1 nM, 0.3 microM and 3.4 microM, respectively. The addition of NO synthase inhibitors N(W)-nitro-L-arginine (L-NOARG), N(G)-monomethyl-L-arginine or 7-nitroindazole reduced BK-induced relaxation by 41+/-6%, 59+/-4% and 51+/-2%, respectively. The inhibition of BK response caused by L-NOARG was completely reversed by L-, but not by D-arginine. Methylene blue and 6-(phenylamino)-5,8-quinolinedione (LY 83583) inhibited the BK response by 88+/-5% and 64+/-4%, while 1H-[1,2,4]oxadiazolo[4,3-a]quinolaxin- -one (ODQ) had no effect. However, ODQ almost abolished SNAP-induced relaxation. Indomethacin and the cyclo-oxygenase 2 (COX-2) inhibitor 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanon e (DFU) caused graded inhibtion of BK responses with mean IC50s of 60 nM and 0.6 nM, respectively. Addition of tetraethylammonium (TEA), charybdotoxin (ChTx), or iberotoxin (IbTx) inhibited BK-induced relaxation by 76+/-4%, 30+/-4% and 99+/-1%, respectively, but the relaxations of PGE2 and cromakalim were unaffected. In contrast, 4-aminopyridine, apamin or glibenclamide did not affect BK-induced relaxation. These results indicate that BK-induced epithelium-dependent relaxation in the guinea pig bronchus is partially mediated by release of NO or by NO-related substances, involving an activation of both cyclo-oxygenase 1 (COX-1) and COX-2 enzymes, through a cyclic guanosine monophosphate (cGMP)-independent mechanism. Furthermore, BK-induced relaxation involves an activation of high-conductance Ca(2+)-activated K+ channels highly sensitive to IbTx, and to a lesser extent to ChTx and TEA.

Ontogenic changes in the fractal geometry of the bronchial tree in Rattus norvegicus

Respiration and metabolism change dramatically over the course of the development of vertebrates. In mammals these changes may be ascribed to organogenesis and differentiation of structures involved in gas exchange and transport and the increase in size. Since young as well as mature individuals must be well-designed if the species is to survive, the physiological changes during the development should be matched with geometrical or structural adjustments of the respiratory system. The aim of this study was to evaluate changes in the fractal geometry of the bronchial tree during the postnatal development of the rat. The average fractal dimension of the bronchial tree of the rats was 1.587, but that of juveniles was larger than that of the adults. We found a significant negative correlation between age and fractal dimension. This correlation could be considered be misleading because of the difficulty of separating age/body size effects. Nevertheless, because fractal dimensions of the bronchial tree of rabbits and humans are known to be similar, 1.58 and 1.57 respectively, the body size effect may be nil. To our knowledge, this is the first report of ontogenetic changes in the fractal dimension of the bronchial tree in mammals.

Tracheobronchial consequences of the use of heat and moisture exchangers in dogs.

PURPOSE: To determine the effect of heat and moisture exchange (HME) on the tracheobronchial tree (TBT) using a unidirectional anesthesic circuit with or without CO2 absorber and high or low fresh gas flow (FGF), in dogs. METHODS: Thirty-two dogs were randomly allocated to four groups: G1 (n=8) valvular circuit without CO2 absorber and high FGF (5 L x min(-1)); G2 (n=8) as G1 with HME; G3 (n=8) circuit with CO2 absorber with a low FGF (1 L x min(-1)); G4 (n=8) as G3 with HME. Anesthesia was induced and maintained with pentobarbital. Tympanic temperature (TT), inhaled gas temperature (IGT), relative (RH) and absolute humidity (AH) of inhaled gas were measured at 15 (control), 60, 120 and 180 min of controlled ventilation. Dogs were euthanized and biopsies in the areas of TBT were performed by scanning electron microscopy. RESULTS: The G2 and G4 groups showed the highest AH (>20 mgH2O x L(-1)) and G1 the lowest (< 10 mgH2O x L(-1)) and G3 was intermediate (< 20 mgH2O x L(-1)) (P < 0.01). There was no difference of TT and IGT among groups. Alterations of the mucociliary system were greatest in G1, least in G2 and G4, and intermediate in G3. CONCLUSION: In dogs, introduction of HME to a unidirectional anesthetic circuit with/without CO2 absorber and high or low FGF preserved humidity of inspired gases. HME attenuated but did not prevent alterations of the mucociliary system of the TBT.

La reactividad de la musculatura bronquial en sujetos jóvenes: patrones en condiciones normales / Bronchial muscle reactivity in young healthy individuals: the pattern in normal conditions

Se analizan críticamente el método presentado en un trabajo anterior en el que se explora, de una manera sencilla, en el hombre, la reactividad de la musculatura de los broquios. Se presentan los resultados obtenidos con este método en 35 sujetos jóvenes sanos. El propósito fue el de encontrar valores que pudieron ser considerados como representativos de los patrones normales para individuos sanos, los cuales podrían servir de base para su comparación con los que se obtengan en los estudios de caso patológicos. Se discute la posibilidad de que la medida de la circunferencia torácica no presente un cambio proporcional de la capacidad pulmonar. Se presentan los resultados de los controles realizados en apoyo de este postulado, uno de los que sirvieron de base para la justificación del método. Se confirma que el músculo liso de los bronquios se encuentra en estado dinámico en las condiciones fisiológicas y que participa en la actividad refleja del sistema nervioso autónomo y en los estados emocionales. Se compara la actividad de este tipo de músculo con la de otros efectos autonómicos

Caracterización de la geometría fractal del árbol bronquial en mamíferos / Measuring the fractal geometry of the bronchial tree in mammals

El árbol bronquial de los mamíferos presenta un diseño que se ha asociado con un adecuado flujo de gases a los alvéolos, una mínima producción de entropía en la mecánica respiratoria y con un mínimo costo en materia y energía. Sin embargo, la vía aérea constituye sólo parte del sistema respiratorio y como tal su geometría debe ajustarse a la función de todo el sistema resolviendo el problema de distribuir un volumen de aire inspirado en una gran superficie, dispuesta en un volumen acotado. Así, la topología bronquial exhibe las características de ocupar espacio con su ramificación progresiva y una reducción del diámetro de los bronquios que se ha asociado a una geometría fractal. En este trabajo se caracteriza la topología del árbol bronquial de Rattus norvegicus mediante su dimensión fractal y se compara con otros mamíferos de distinto tamaño: Oryctolagus cuniculli y Homo sapiens. Se estudia además el efecto de la escala para verificar la autosimilitud. Los resultados demuestran una geometría fractal de la vía aérea de las tres especies, que se mantiene a distintas escalas y son una demostración directa de este tipo de geometría. La topología se mantiene invariante en las tres especies, con dimensiones fractales entre 1,57 y 1,59. Los resultados coinciden con otros estudios realizados en la vía aérea, la superficie alveolar, la ventilación y la perfusión pulmonar. Se discuten las consecuencias de este tipo de geometría en el pulmón

Traqueobronquite necrotisante: relato de um caso em lactente / Necrotizing tracheobronchitis in an infant

Objetivo: Alertar os pediatras emergencistas para uma causa pouco comum de obstruçäo de vias aéreas em crianças submetidas a ventilaçäo mecânica. Métodos: Os autores relatam um caso de traqueobronquite necrotisante em lactente de 8 meses e discutem a fisiopatologia, diagnóstico e abordagem terapêutica. Resultados: A crianca apresentou evoluçäo favorável associado ao diagnóstico precoce e pronta intervençäo broncoscópica. Conclusöes: Os pediatras emergencistas devem suspeitar de traqueobronquite necrotisante em todas as crianças sob ventilaçäo mecânica que apresentarem o quadro clínico típico caracterizado por obstruçäo aguda das vias aéreas, hiperinsuflaçäo pulmonar, mesmo fora do período neonatal. Essa situaçäo, uma vez reconhecida, constitui indicaçäo precisa de traqueobroncoscopia de urgência...

Método no invasivo para explorar la actividad de la musculatura bronquial. valoración de la resistencia de las vías aéreas / Non-invasive trial for the assessment of the brinchial musculature. An evaluation of the airway resistance

Se presenta un método sencillo para explorar las funciones de la musculatura bronquial en el hombre. Fueron empleados individuos sanos voluntarios y algunos pacientes neumológicos. La respiración fue registrada con un neumógrafo colocado en la base del tórax y el flujo de aire con un neumotacógrafo de Fleisch acoplado a una mascarilla ordinaria. Se midió la amplitud máxima de los trazos: en condiciones de reposo; durante y después de una inspiración profunda, de un periodo breve de apnea voluntaria, de la maniobra de Valsalva, o de la aplicación de un ruido súbito. Con las medidas se estableció la relación P/V (presión intra-torácica/volumen pulmonar) se graficaron los datos obtenidos. Se encontró que la musculatura bronquial cambia en su resitencia al flujo de aire, tanto en las condiciones de control como en las manifestaciones reflejas evocadas por las maniobras experimentales empleadas y los estados emocionales, siguiendo las reacciones del sistema nervioso autónomo. Se concluye que a pesar de los diversos factores de error, el método puede ser muy útil para explorar la reactividad del músculo liso de los bronquios en situaciones normales y eventualmente en algunas patológicas

Efeitos da poluiçäo, tabagismo e poeiras minerais sobre o aparelho respiratório / Effects of pollution, smoking and mineral dusts on respiratory system

Doenças pulmonares intersticiais difusas e doenças crônicas das vias aéreas podem ser causadas por poeiras minerais, poluiçäo e fumo e säo discutidas neste trabalho. Doenças pulmonares ocupacionais e ambientais constituem assunto amplo e complexo, impossível de ser abordado em sua íntegra em um simples trabalho, de modo que daremos destaque a conceitos básicos envolvendo mecanismos de defesa pulmonar e um pouco da experiência prática na rotina diagnóstica. Nos pulmöes, doenças intersticiais ocupacionais säo o resultado final da composiçäo de lesöes focais. Esses sítios de lesöes focais traduzem a resposta do tecido pulmonar alveolado e condutor ao fumo, particulas ou minerais. Com a injúria pulmonar crescente e repetitiva, inflamaçäo e fibrose determinam distorçäo e remodelaçäo pulmonar, finalmente conduzindo a alteraçöes da fisiologia respiratória. Nos alvéolos, o macrófago pulmonar parece ter um papel central no desenrolar desses eventos, agindo tanto como fagócito incorporador de particulas quanto como mediador liberador de poderosas substâncias biológicas modificadoras da funçäo de outras células, como neutrófilos e fibroblastos

On the phasic reflex bronchodilation in the cat.

In records of tracheal pressure or flow taken from anesthetized cats appear large pressure-negative, or air inflow excursions, in response to single pulses applied to the central end of the vagus nerve. These responses have been attributed to phasic bronchodilation and not only due to the brief contractions of inspiratory muscles that occur as part of the total responses. Phasic bronchodilation responses appear mainly during inspiration but they may also occur in the expiratory phase through facilitation, during post-hyperventilatory apnea or that induced by constant current (d.c.) vagal stimulation. They are significantly reduced after lung sympathectomy. These bronchomotor responses showed long term depression (LTD) after spontaneous or reflexly evoked hiccups, and long term potentiation (LTP) after repetitive, or d.c. vagal stimulation. They are also potentiated on the experimental conditions that include exaggerated sympathetic activity. These and some other characteristics described indicate that bronchomotor responses are legitimate and can be used to follow the changes in excitability of the central generator of breathing.

Airway and pulmonary tissue responses to capsaicin in guinea pigs assessed with the alveolar capsule technique.

We studied the effects of capsaicin on airway and lung tissue mechanics in anesthetized and tracheostomized guinea pigs that were mechanically ventilated at constant tidal volume (8 ml/kg) and breathing frequency (60 breaths/min). Dose-response curves to intravenously infused capsaicin (1, 10, and 100 micrograms/kg) were performed (five animals for each dose, one dose per animal). We measured airflow, volume (by integration of the flow signal), tracheal pressure, and alveolar pressure with an alveolar capsule. Capsaicin induced a dose-dependent increase in airway resistance, tissue resistance, and dynamic elastance. The relationship between airway pressure and flow was fitted by a quadratic (Rohrer) equation. Airflow became more turbulent after infusion of capsaicin. After infusion of 100 micrograms/kg capsaicin, airway pressure (at flow rates of 10 ml.s-1) increased from 3.03 +/- 0.40 (mean +/- SEM) to 9.58 +/- 1.88 cm H2O, whereas the pressure corresponding to viscoelastic properties of lung tissue increased from 0.92 +/- 0.14 to 8.58 +/- 1.12 cm H2O. We conclude that infusion of capsaicin results in mechanical effects in both airways and pulmonary tissue.

Potassium channel opening drugs and the airways.

1. Potassium channel opening drugs (KCOs) include benzopyrans such as cromakalim, cyanoguanidines such as pinacidil and tetrahydrothiopyrans such as RP 49356. 2. While clinical trials have indicated that cromakalim may be of benefit in the treatment of nocturnal asthma, it remains to be determined whether KCOs will find a place in our armamentarium of clinically useful anti-asthma agents. 3. KCOs inhibit the spontaneous tone of airways smooth muscle in vitro, an action associated with membrane hyperpolarization towards the potassium equilibrium potential and with the promotion of 86Rb+ or 42K+ efflux from the muscle cells. KCOs suppress spasm of airways smooth muscle evoked by low (< 40 mM) but not high (> 40 mM) concentrations of KCl. Their relaxant effects in airways smooth muscle can be attenuated by a variety of agents (including sulphonylureas) known to inhibit the opening of plasmalemmal K(+)-channels. 4. The KCOs open an ATP-sensitive K(+)-channel (KATP) in the plasmalemma. KATP is not open under normal circumstances and does not play an important role in determining the strong outward rectifying behavior of the cell membrane. The biochemical mechanisms by which the KCOs promote the opening of KATP remain to be elucidated but probably do not involve channel phosphorylation consequent to the intracellular accumulation of cAMP. 5. By causing hyperpolarization of the plasmalemma, the KCOs inhibit the cellular influx of Ca2+ through voltage-dependent channels. Relaxation follows both as a direct consequence of the fall in cytosolic free Ca2+ and also as a consequence of reduced production of phosphoinositide second messengers. The KCOs may also inhibit Ca2+ uptake by, and hence Ca2+ release from, the sarcoplasmic reticulum. 6. KCOs can inhibit cholinergic and non-adrenergic, non-cholinergic (NANC) excitatory neuroeffector transmission in the airways by glibenclamide-sensitive mechanisms which may involve inhibition of neurotransmitter release. The KCOs do not attenuate NANC inhibitory neuroeffector transmission, suggesting that KATP may not be expressed in neurones of this type. 7. The active enantiomer of cromakalim has been found to be effective in alleviating nocturnal asthma at plasma concentrations just threshold for relaxing human airways smooth muscle in vitro. The clinical efficacy of cromakalim may therefore depend on an action other than the direct relaxation of airways smooth muscle. Animal studies indicate that KCOs can reduce airway hyper-reactivity at sub-bronchodilator doses. The mechanism of this effect remains to be elucidated and may not crucially depend upon inhibition of neurotransmitter release within the lung.