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PubMed1992

Chasing the elusive animal model of late-phase bronchoconstriction: studies in dogs, guinea pigs and rats.

Antigen inhalation in sensitized dogs, guinea pigs and rats resulted in a marked, late-phase, eosinophil-rich, influx of inflammatory cells into the bronchial lumen. Attempts to demonstrate an associated late-phase bronchoconstriction were disappointing. We were unable to demonstrate a late-phase bronchoconstriction in either rats or dogs, even when dogs were pretreated with metyrapone to reduce blood cortisol levels. In ovalbumin-sensitized guinea pigs, challenged with low doses of ovalbumin, we observed an immediate bronchoconstriction, a late-phase bronchopulmonary eosinophilia but no late-phase bronchoconstriction. However, inhalation of very high doses of antigen in mepyramine-treated sensitized guinea pigs did induce a moderate late-phase bronchoconstriction.

Animals↗

PubMed1989

Effect of cyclosporin A and the platelet-activating factor (PAF) antagonist, BN 52021, on PAF- and antigen- induced bronchoconstriction in the guinea-pig.

The effects of the PAF antagonist, BN 52021, and cyclosporin A (CsA), either alone or in combination, on PAF- and antigen- induced bronchoconstriction were investigated in control and passively sensitized guinea-pigs, respectively. Although single administration of CsA alone has no effect on the PAF-induced bronchoconstriction, a marked inhibition of this phenomenon is observed when the drug is given along with an inactive dose of BN 52021. This effect of the association of the two drugs on the bronchoconstriction is also related to an action on the PAF-induced alterations in the number of leukocytes and platelets. In addition, administration of CsA for 48 hrs, which alone does not influence PAF-induced bronchoconstriction, markedly increases the inhibition evoked by BN 52021. Although bolus administration of CsA has no effect on the antigen -induced bronchoconstriction, a marked inhibition of this phenomenon is observed when the drug is given for 2 days. This inhibition by CsA is not further enhanced when the animals are also treated with BN 52021. These results strengthen the hypothesis that PAF and the immune system are involved in the regulation of bronchopulmonary reactions.

Animals↗

PubMed1986

Effects of PAF-acether and structural analogues on platelet activation and bronchoconstriction in guinea-pigs.

PAF-acether (platelet-activating factor) (1-O-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine) induces platelet-dependent bronchoconstriction in the guinea-pig which correlates with its in vivo thrombocytopenic effect. We investigated the influence of modifications of the polar head group in position 3 of the glycerol skeleton of PAF-acether on guinea-pig platelet activation and bronchoconstriction. PAF-acether itself induced concentration-dependent platelet activation (EC50 for aggregation = 0.41 nM and EC20 for secretion of ATP = 0.56 nM). The 3-phosphoryl-N-methyl-morpholino ethanol analogue was slightly more active than PAF-acether and the 3-phosphoryl-N-methyl-piperidinium ethanol, 3-phopshoryl-(N-methyl-piperidino-3') methanol and 3-phosphoryl-(N-methyl-hydroxy-4') piperidine analogues were equieffective to PAF-acether in activating platelets. The 3-phosphoryl-piperidino ethanol analogue was 8 times less active than PAF-acether; the 3-phosphoryl-morpholino ethanol analogue and the 1-O-octadecyl-2-O-acetyl-3-O-[trimethyl-ammonio)-propyl) glycerol were inactive up to 1 microM. Our data show that the choline head group is not a compulsory requirement for activity. When injected i.v. to the propranolol-treated guinea-pigs, the platelet-activating analogues also induced bronchoconstriction. Two PAF-acether antagonists, compounds 48740 RP and BN 52021, inhibited PAF-acether-induced platelet activation when added to PRP at the final concentration of 0.1 mM (aggregation inhibited by 91 +/- 4 and by 94 +/- 3% respect.; secretion inhibited by 80 +/- 12 and 79 +/- 10% respectively, mean +/- S.E.M., n = 4). Both antagonists also suppressed platelet activation and in vivo bronchoconstriction, thrombocytopenia, leukopenia and hypotension induced by PAF-acether and the various analogues. Our results indicate that PAF-acether and the analogues studied trigger platelet activation and the consequent bronchoconstriction through mechanisms which share sensitivity to same antagonists.

Adenosine Triphosphate↗

PubMed1990

Ganglion-blocking agents enhance neurally mediated bronchoconstriction in the guinea-pig: possible role of sensory neuropeptides.

The effect of ganglion blockade by hexamethonium bromide (0.1-100 mumol.kg-1) and pentolinium tartrate (0.01-3 mumol.kg-1) on the bronchoconstriction induced by vagal nerve stimulation (15 Hz, 0.2 ms, 3 s, 7-20 V) was evaluated in the anaesthetized guinea-pig. Both ganglion-blocking agents potentiated this response dose dependently. When the neural bronchoconstriction was suppressed by atropine, hexamethonium restored this response dose dependently. Hexamethonium produced inhibitory effects on vagally induced bronchoconstriction in capsaicin-desensitized and in propranolol- or reserpine-pretreated guinea-pigs. Propranolol (0.03-3 mumol.kg-1) produced a marked dose-dependent increase of neural bronchoconstriction (which was markedly reduced, about 10 times) in capsaicin-desensitized animals. Our results show that ganglion-blocking agents potentiate neural bronchoconstriction in the guinea-pig and that sensory neuropeptides may have a role in this effect. Moreover, beta-adrenergic modulation of the release of neuropeptides from vagal sensory fibers is suggested.

Anesthesia↗

PubMed1988

Effect of gallopamil, a calcium channel blocker, on carbachol- and histamine-induced bronchoconstriction in sheep.

We compared the in vivo effectiveness of the calcium channel blockers, gallopamil and verapamil, in inhibiting carbachol- and histamine-induced bronchoconstriction in conscious sheep. In 13 sheep, specific lung resistance (SRL) was measured before and after aerosol challenge with histamine (50 breaths; 5% solution) and carbachol (10 breaths; 2.5% solution), without and with pretreatment with intravenous and aerosolized gallopamil and verapamil. Histamine increased mean SRL by 213%. Intravenous (20 micrograms/kg) and aerosolized (5 mg) gallopamil markedly inhibited the histamine-induced bronchoconstriction. Mean SRL increased by 19% and 23%, respectively, whereas 2.5 mg of aerosolized gallopamil partly inhibited the histamine-induced response with SRL increasing by 115% (p less than 0.05). Carbachol increased mean SRL by 380%. Pretreatment with 2.5 mg of aerosolized gallopamil had no effect on carbachol-induced bronchoconstriction, whereas intravenous and 5 mg of aerosolized gallopamil partly attenuated the carbachol response; mean SRL increased by 204% and 177%, respectively (p less than 0.05). Intravenous (150 micrograms/kg) and aerosolized (10 mg and 20 mg) verapamil did not prevent either histamine- or carbachol-induced bronchoconstriction. These results indicate that gallopamil (parenteral and aerosol) attenuates carbachol- and histamine-induced bronchoconstriction, is more potent than verapamil, and may be of therapeutic potential.

Aerosols↗

PubMed1989

Effect of indomethacin on adenosine-induced bronchoconstriction.

The exact mechanism of adenosine-induced bronchoconstriction in patients with asthma is unknown. Adenosine contraction of guinea pig trachea was antagonized by inhibitors of cyclooxygenase. The aim of this study was to investigate the effect of indomethacin (100 mg/day) on adenosine-induced bronchoconstriction in 14 asymptomatic patients with asthma. Airway response was evaluated as FEV1, and adenosine was administered as an aerosol diluted in 0.9% saline to produce a concentration range of 0.125 to 4 mg/ml. The dose of adenosine producing a 20% change in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curve; the results of PD20 were converted to log values for statistical analysis (Student's paired t test). The study was performed on 3 separate days. On the first day, the adenosine challenge was performed, and on subsequent days patients were pretreated with either placebo or indomethacin in a randomized, double-blind manner. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 0.71 mg (95% confidence limits, 0.44 to 1.16). After placebo, a geometric mean PD20 of 0.91 mg (95% confidence limits, 0.53 to 1.58) was obtained. Indomethacin pretreatment decreased adenosine hyperresponsiveness and shifted the dose-response curves of adenosine challenge to the right with a geometric mean PD20 of 1.28 mg (95% confidence limits, 0.64 to 2.56). The effect of indomethacin on adenosine bronchoconstriction (p less than 0.01 versus baseline; p less than 0.05 versus placebo) suggests an indirect mechanism of adenosine on inducing release of arachidonic acid derivatives. Inflammatory mediators inhibited by indomethacin may be involved in adenosine bronchoconstriction, even if this mechanism is not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1997

Effect of angiotensin II on histamine-induced bronchoconstriction in the human airway both in vitro and in vivo.

The renin-angiotensin system is activated in acute severe asthma. Angiotensin II causes bronchoconstriction in mild asthmatics and potentiates methacholine-evoked bronchoconstriction both in vitro and in vivo. To evaluate the effect of angiotensin II on histamine-induced bronchoconstriction, human bronchial rings (n = 6) were obtained from lung tissue at thoracotomy and were prepared in organ baths. Contractions were measured isometrically and cumulative concentration-response curves obtained to angiotensin II alone and to histamine in the presence and absence of threshold concentrations of angiotensin II. Eight asthmatic patients with bronchial hyper-reactivity to histamine were challenged with histamine during intravenous infusion of placebo, angiotensin II 1 ng kg-1 min-1 and angiotensin 2 ng kg-1 min-1 administered in a randomized, double-blind fashion, FEV1 was measured prior to, during the infusion and during the histamine challenge. Angiotensin II (3 x 10(-7)M and 10(-6)M) alone evoked small contractions (< 0.25 g) of human bronchi in vitro, but pre-incubation with threshold concentrations of angiotensin II (10(-7)M, 3 x 10(-7)M and 10(-6)M) had no effect on histamine-evoked contractions. In asthmatic patients, angiotensin II alone had no effect on baseline FEV1 at the low levels infused and did not affect the response to nebulized histamine as measured by the PC20 histamine: Geometric mean (range) PC20 histamine (mg ml-1) screening day 3.58 (1.26-7.75), placebo infusion 2.67 (0.89-9.57), angiotensin II 1 ng kg-1 min-1 2.45 (0.42-6.97) and angiotensin II 2 ng kg-1 3.09 (0.8-10.78). It is concluded that, in contrast to its potentiating effect on methacholine-induced bronchoconstriction, angiotensin II has no effect on histamine-evoked bronchoconstriction in human bronchi in vitro or in vivo.

Adult↗

PubMed1975

Hypocapnic bronchoconstriction and inhalation anesthetics.

The effects of halothane, enflurane, and methoxyflurane on hypocapnic bronchoconstriction (increased airway resistance and decreased compliance of the lung) were studied in vivo in the isolated left lower lobe of the canine lung. Hypocapnic bronchoconstriction, induced by altering the concentration of CO2 in gas ventilating the lobe, was repeated in the presence and absence of various concentrations of anesthetic gases (halothane: 0.5, 1.0, and 3.0 per cent; enflurane: 1.0, 3.0, and 5.0 per cent; methoxyflurane: 0.25, 0.50, and 1.0 per cent). In the higher concentrations, all three drugs blocked the bronchoconstrictor effect produced when the inspired CO2 was decreased from 5 to 0 per cent. In lower concentrations, halothane was the most effective blocking drug. Propranolol did not affect the ability of the three anesthetics to block hypocapnic bronchoconstriction, nor did the beta-receptor blocking drug sotalol affect the blocking effects of halothane. The ability of these anesthetics to block hypocapnic bronchoconstriction probably is mediated not through an adrenergic mechanism but by one that is nonspecific. (Key words: Lung, bronchoconstriction; Carbon dioxide, hypocarbia; Anesthetics, volatile, halothane; Anesthetics, volatile, enflurane; Anesthetics, volatile, methoxyflurane.)

Adrenergic beta-Antagonists↗

PubMed1986

Characterization of substance P-induced bronchoconstriction in the guinea-pig: a comparison with acetylcholine.

Substance P (0.5-8.0 micrograms/kg, i.v.) induced bronchoconstriction in anaesthetized, mechanically-ventilated guinea-pigs, comprising increases in airways resistance and decreases in dynamic compliance. These bronchoconstrictor responses were unaffected by bilateral vagotomy, pretreatment with pheniramine (2 mg/kg, i.v.) or by pretreatment with atropine (100 micrograms/kg, i.v.). Acetylcholine-induced (4-32 micrograms/kg, i.v.) bronchoconstriction was prevented by atropine pretreatment, whereas bilateral vagotomy inhibited responses to acetylcholine. Ganglionic blockade using hexamethonium (20 mg/kg, i.v.) potentiated both substance P and acetylcholine on airways resistance and dynamic compliance. Indomethacin (1 or 5 mg/kg, i.v.) did not affect substance P-induced bronchoconstriction, whereas the higher dose enhanced acetylcholine-induced increases in airways resistance. In addition, aspirin pretreatment (20 mg/kg, i.v.) did not alter the bronchoconstrictor potency for either substance P or acetylcholine. On the other hand, the combined cyclo-oxygenase/lipoxygenase inhibitors eicosatetraynoic acid (ETYA, 20 mg/kg, i.v.) and BW755C (20 mg/kg, i.v.) potentiated both acetylcholine and substance P on airways resistance and dynamic compliance. The results suggest that substance P-induced bronchoconstriction may be modulated by the sympathetic nervous system and does not appear to be influenced by vagal or histaminergic mechanisms. The failure of indomethacin or aspirin to affect substance P-induced bronchoconstriction, together with the enhancing effects of ETYA and BW755C pretreatments, provide evidence consistent with the existence of a bronchodilator mechanism which may be inhibited by compounds inhibiting lipoxygenase enzymes.

Acetylcholine↗

PubMed1983

An in vivo model for measuring antigen-induced SRS-A-mediated bronchoconstriction and plasma SRS-A levels in the guinea-pig.

1 Pharmacological modulation of antigen-induced anaphylaxis in actively sensitized guinea-pigs with intravenously administered indomethacin (10 mg/kg), pyrilamine (2.0 mg/kg) and propranolol (0.1 mg/kg) resulted in a delayed onset, slowly developing bronchoconstriction indicative of a slow-reacting substance of anaphylaxis (SRS-A) response. 2 Measurements of pulmonary mechanics on the drug-pretreated animals challenged with ovalbumin demonstrated a more prominent effect on dynamic compliance than resistance. This is consistent with the more potent effects of SRS-A on peripheral rather than central airways. 3 The slowly developing bronchoconstriction obtained after treatment with indomethacin, pyrilamine and propranolol was inhibited by the standard SRS-A antagonist, FPL 55712 and the SRS-A synthesis inhibitors, phenidone, BW 755C and nordihydroguaiaretic acid. 4 Plasma SRS-A levels were determined in guinea-pigs following antigen challenge. The appearance of SRS-A in the plasma preceded the onset of bronchoconstriction and SRS-A levels remained elevated throughout its development. Coincident with the inhibition of bronchoconstriction by the SRS-A synthesis inhibitor, phenidone, was a dose-dependent reduction in plasma SRS-A. The intravenous ED50 in each case was 4 mg/kg. 5 This model of antigen-induced SRS-A-mediated bronchoconstriction should prove useful for the in vivo evaluation and development of therapeutics which regulate the synthesis of SRS-A.

Animals↗

PubMed1988

Interference of the Paf antagonist Ro 19-3704 with Paf and antigen-induced bronchoconstriction in the guinea-pig.

1. In vitro, Ro 19-3704, a structurally related antagonist of platelet-activating factor (Paf) inhibited selectively rabbit platelet aggregation. In vivo, administered intravenously, it inhibited bronchoconstriction, leukopenia, thrombocytopenia and the accompanying accumulation of platelet aggregates in guinea-pig lung microvessels induced by i.v. Paf. Administered by aerosol, Ro 19-3704 failed to inhibit bronchoconstriction, thrombocytopenia or leukopenia due to i.v. Paf. 2. Bronchoconstriction induced by Paf, in aerosol form, was blocked by Ro 19-3704 administered by the i.v. or aerosol route, which suggests that it interacts with pulmonary cells responsible for bronchoconstriction. 3. Ro 19-3704 has free radical scavenging properties, since it inhibited the production of superoxide anions by macrophages stimulated by Paf and by N-formyl-methionyl-leucyl-phenylalanine (FMLP). Ro 18-7715, another Paf antagonist and analogue of Ro 19-3704, failed to inhibit the production of superoxide anions by macrophages stimulated by FMLP at concentrations which were effective against Paf. 4. Administered intravenously, Ro 19-3704 failed to block bronchoconstriction induced by an i.v. injection of ovalbumin to guinea-pigs passively sensitized with anti-ovalbumin antiserum. Passive pulmonary anaphylaxis due to an aerosol of ovalbumin was blocked by i.v. Ro 19-3704.

Aerosols↗

PubMed1988

Opioid modulation of non-cholinergic neural bronchoconstriction in guinea-pig in vivo.

1. Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non-cholinergic (NC) neural bronchoconstriction in guinea-pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea-pig. 2. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea-pigs which was reduced by atropine (1 mg kg-1), but the NC component was unaffected by hexamethonium (10 mg kg-1). 3. NC bronchoconstriction was reduced by morphine in a dose-dependent manner (ED50 = 132 micrograms kg-1 with a maximal inhibition of 79 +/- 2.1% at 1 mg kg-1). Yohimbine (0.5 mg kg-1) did not alter the inhibitory effect of morphine (1 mg kg-1). 4. The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg-1) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg-1) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. 5. The selective mu-opioid receptor agonist Tyr-(D-Ala)-Gly-(N-Me-Phe)-Glyol (DAGOL) was significantly more potent than morphine with an ED50 of 5.4 micrograms kg-1 and complete inhibition at 100 micrograms kg-1. The delta-agonist Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE) was less potent than DAGOL with an ED50 of 28 micrograms kg-1 and a maximal inhibition of only 50 +/- 5% at 100 micrograms kg-1. The delta-agonist Tyr4D-Pen)-Gly-Phe-D-Pen) (DPDPE) was less potent than DAGOL with an ED5o of 28pgkg-1 and a maximal inhibition of only 50 + 5% at lOOPgkg- . The Kappa-receptor agonist, U-50,488H had no inhibitory effect on the NC bronchoconstrictor response. 6. The bronchoconstrictor responses to exogenous substance P (25 pgkg- 1) or acetylcholine (25 pg kg- 1) were unaffected by morphine (500 pg kg- 1). 7. We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on mu-opioid receptors localized to sensory nerve endings in the airway.

Acetylcholine↗

PubMed1990

Mechanism of the potentiation of neurally-induced bronchoconstriction by gallamine in the guinea-pig.

1. Electrical stimulation of the cervical vagi (15 Hz, 0.2 ms, 3 s, 7-15 V) produced a slight bronchoconstriction in the anaesthetized guinea-pig. This effect was fully abolished by atropine, while gallamine (0.1-10 mumol kg-1) produced a dose-dependent increase up to ten fold. 2. Gallamine-induced potentiation of neurally-mediated bronchoconstriction was not inhibited by depletion of sensory neuropeptides with capsaicin or by pretreatment with pyrilamine. In propranolol-pretreated guinea-pigs the potentiation induced by gallamine 3 and 10 mumol kg-1 was inhibited by 40 and 46%, respectively. 3. Physostigmine (0.5 mg kg-1) produced a very slight and slowly developing bronchoconstriction in the anaesthetized guinea-pig, which was also potentiated dose-dependently by gallamine (0.1-10 mumol kg-1). 4. Gallamine (10 mumol kg-1) potentiated the bronchial anaphylactic response induced by aerosol challenge with ovalbumin in actively sensitized guinea-pigs. 5. These results suggest that neither sensory neuropeptides nor histamine are involved in the gallamine-induced potentiation of neurally-mediated bronchoconstriction, while inhibition of the sympathetic nervous system may play a minor role. They are in general agreement with the hypothesis that gallamine antagonizes acetylcholine selectively at prejunctional muscarinic receptors in the guinea-pig airways, thus increasing its release from parasympathetic nerve terminals. These autoreceptors appear to be operant during anaphylactic bronchoconstriction.

Acetylcholine↗

PubMed1988

Pharmacological modulation of platelet activating factor (PAF)-induced bronchoconstriction and hypertension in anaesthetized guinea-pigs.

The effect of PAF has been examined in anaesthetized guinea-pigs. Intravenous (i.v.) administration of PAF (10 ng kg-1) did not modify the respiratory response but decreased the arterial blood pressure. A high dose of PAF (200 ng kg-1) caused marked bronchoconstriction and concomitant hypertension. The cyclooxygenase inhibitors aspirin (5 mg kg-1) and indomethacin (5 mg kg-1) and the thromboxane A2 (TXA2) receptor antagonist BM-13.177 (1 mg kg-1) failed to inhibit the peak bronchoconstrictive response but significantly inhibited the prolonged response following peak response. These inhibitors also attenuated PAF-induced hypertension. On the other hand, the lipoxygenase inhibitors phenidone (10 mg kg-1) and NDGA (5 mg kg-1) and the leukotriene (LT) receptor antagonist FPL-55712 (2 mg kg-1) affected neither bronchoconstriction nor hypertension induced by PAF. However, when aspirin was given in combination with NDGA, phenidone or FPL-55712, the peak and the following prolonged bronchoconstriction were significantly inhibited. The suppression of PAF-induced hypertension by aspirin was not further inhibited by the combination of these inhibitors. These results indicate that in anaesthetized guinea-pigs PAF-induced bronchoconstriction is composed of a dual response, a direct action (peak response) and an indirect action (prolonged response). The latter may be produced by the generation of TXA2 and lipoxygenase products, while PAF-induced hypertension is indirectly mediated by the generation of TXA2.

Animals↗

PubMed1986

Do asthmatics suffer bronchoconstriction during rapid eye movement sleep?

Many patients with asthma are troubled by nocturnal wheeze. The cause of this symptom is unknown, but sleep is an important factor. A study was carried out to determine whether nocturnal bronchoconstriction is related to any specific stage of sleep. Eight asthmatics with nocturnal wheeze and eight control subjects performed forced expiratory manoeuvres immediately after being woken from rapid eye movement (REM) or non-REM sleep, wakings being timed to differentiate temporal effects from those related to the stage of sleep. The control subjects showed no significant temporal bronchoconstriction or bronchoconstriction related to the stage of sleep. All patients showed bronchoconstriction overnight, the mean peak expiratory flow rate falling from 410 (SEM 50) 1/min before sleep to 186 (49)1/min after sleep. After the patients had been woken from REM sleep the forced expiratory volume in one second was on average 300 ml lower (p less than 0.02) and peak expiratory flow rate 45 1/min lower (p less than 0.03) than after they had been woken from non-REM sleep. As wakenings from REM sleep were 21(8) minutes later in the night than those from non-REM sleep multivariate analysis was performed to differentiate temporal effects from those related to the stage of sleep. This showed that the overnight decreases in forced expiratory volume in one second and peak expiratory flow rate were significantly related both to time and to REM sleep. This study suggests that asthmatics may suffer bronchoconstriction during REM sleep.

Adolescent↗

PubMed1984

Interaction of sulfur dioxide and dry cold air in causing bronchoconstriction in asthmatic subjects.

To determine whether sulfur dioxide and airway cooling and drying interact in causing bronchoconstriction in persons who have asthma, we measured specific airway resistance in seven asthmatic subjects before and after they performed voluntary eucapnic hyperpnea for 3 min breathing four different gas mixtures. The mixtures, which the subjects breathed through a mouthpiece in random order on 4 different days, were 1) humidified room-temperature air, 2) humidified room-temperature air containing 0.5 ppm SO2, 3) cold dry air, and 4) cold dry air containing 0.5 ppm SO2. Each subject breathed at a rate and depth known from preliminary studies to cause little or no bronchoconstriction when that subject inhaled 0.5 ppm SO2 in humidified room-temperature air or cold dry air. When given independently in the blinded study, 0.5 ppm SO2 or cold dry air again caused insignificant bronchoconstriction, but when given together the two stimuli caused significant bronchoconstriction, as indicated by an increase in specific airway resistance from 6.94 +/- 2.85 to 22.35 +/- 10.28 l X cmH2O X l-1 X s (mean +/- SD) (P less than 0.001). thus airway cooling and/or drying increases the bronchoconstriction induced by inhaled SO2 in persons who have asthma. This increase suggests that persons who have asthma may be more sensitive to the bronchoconstrictor effects of ambient SO2 in cold dry environments than in warm moist environments.

Adult↗

PubMed1987

Density dependence of maximal flow is lung volume dependent during bronchoconstriction.

We examined the changes in maximum expiratory flow (Vmax) and the density dependence of maximum expiratory flow (delta Vmax) during histamine-induced bronchoconstriction in dogs. Histamine acid phosphate solution was nebulized into the airways of six dogs to produce predominantly peripheral airway obstruction. Vmax air, Vmax with the dogs breathing 80% He-20% O2 (delta Vmax), and airway sites of flow limitation (choke points) were examined at four lung volumes (VL), which ranged from 51 to 23% of the control vital capacity (VC). The findings were interpreted in terms of the wave-speed theory of flow limitation. At all VL, Vmax air decreased during bronchoconstriction by approximately 30% compared with the control value. Resistances peripheral to a 0.3-cm-diam airway were increased about threefold with histamine, whereas resistances between 0.6-cm-diam bronchi and main-stem bronchi increased just slightly. Airway diameters were measured in the air-dried lung at 20 cmH2O transpulmonary pressure. Our results showed that only at 44% VC did delta Vmax decrease in all experiments after histamine to indicate peripheral obstruction (mean: 68.5 to 45%). At 23% VC, delta Vmax increased slightly, from 22 to 28%. At 23 and 36% VC, substantial differences in the wave-speed variables between air and HeO2 were present before bronchoconstriction, so that delta Vmax was low in some dogs, although peripheral airway obstruction was not evident. When bronchoconstriction was produced, delta Vmax at 23% VC could not be decreased further and even increased in four of six dogs. Thus changes in delta Vmax at given lung volume may not reflect the predominant site of airflow obstruction during bronchoconstriction.

Airway Obstruction↗

PubMed1987

Respiratory changes in thoracic muscle length during bronchoconstriction.

The purpose of the present study was to assess the effects of bronchoconstriction on respiratory changes in length of the costal diaphragm and the parasternal intercostal muscles. Ten dogs were anesthetized with pentobarbital sodium and tracheostomized. Respiratory changes in muscle length were measured using sonomicrometry, and electromyograms were recorded with bipolar fine-wire electrodes. Administration of histamine aerosols increased pulmonary resistance from 6.4 to 14.5 cmH2O X l-1 X s, caused reductions in inspiratory and expiratory times, and decreased tidal volume. The peak and rate of rise of respiratory muscle electromyogram (EMG) activity increased significantly after histamine administration. Despite these increases, bronchoconstriction reduced diaphragm inspiratory shortening in 9 of 10 dogs and reduced intercostal muscle inspiratory shortening in 7 of 10 animals. The decreases in respiratory muscle tidal shortening were less than the reductions in tidal volume. The mean velocity of diaphragm and intercostal muscle inspiratory shortening increased after histamine administration but to a smaller extent than the rate of rise of EMG activity. This resulted in significant reductions in the ratio of respiratory muscle velocity of shortening to the rate of rise of EMG activity after bronchoconstriction for both the costal diaphragm and the parasternal intercostal muscles. Bronchoconstriction changed muscle end-expiratory length in most animals, but for the group of animals this was statistically significant only for the diaphragm. These results suggest that impairments of diaphragm and parasternal intercostal inspiratory shortening occur after bronchoconstriction; the mechanisms involved include an increased load, a shortening of inspiratory time, and for the diaphragm possibly a reduction in resting length.

Animals↗