Bronchial Cross-sectional Area Research Articles

Milrinone Attenuates Serotonin-Induced Pulmonary Hypertension and Bronchoconstriction in Dogs

We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg · kg−1 · h−1). Bronchoconstriction and PH were elicited by 5HT (10 μg/kg + 1.0 mg · kg−1 · h−1). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 μg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 μg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% ± 27% and decreased percentage of bronchial cross-sectional area to 52% ± 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, −log 50% effective concentration (mean ED50 in μg/kg) of milrinone for bronchoconstriction: 4.32 ± 0.13 (47.6) was significantly smaller than that for PH: 3.84 ± 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 μg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by β-adrenoceptor activation because β-blocker did not antagonize. Implications: We studied the effects of milrinone on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Milrinone produces pulmonary vasodilation and bronchodilation, whose effects may not be caused by β-adrenoceptor activation. In addition, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than that in pulmonary vascular smooth muscle.

I.V. Lidocaine Worsens Histamine-Induced Bronchoconstriction in Dogs

HIROTA, K.; HASHIMOTO, Y.; SATO, T.; YOSHIOKA, H.; KUDO, T.; ISHIHARA, H.; MATSUKI, A. Author Information

Prostaglandin E1 produces spasmolytic effects on histamine-induced bronchoconstriction in dogs.

In this study, we evaluated the spasmolytic effect of intravenous prostaglandin (PG) E1 on histamine-induced bronchoconstriction with a direct visualization method using a superfine fiberoptic bronchoscope. A university research laboratory. Mongrel dogs. The bronchial cross-sectional area (BCA) of mongrel dogs was measured by a direct visualization method using a superfine fiberoptic bronchoscope. Bronchoconstriction was elicited with histamine (H) infusion: 10 microg/kg iv bolus + 500 microg/kg/h continuous iv. The first protocol (n = 7) was designed to determine the effects of intravenous bolus of PGE1: 0 (saline), 0.01, 0.1, 1.0 and 10 microg/kg on H-induced bronchoconstriction. BCA was assessed before and 30 min after starting the H infusion and 5 min after each dose of intravenous PGE1. The second protocol was designed to determine whether continuous intravenous infusion of PGE1 reverses H-induced bronchoconstriction. In the PG group (n = 6), PGE1 was continuously infused at 0.1 microg/kg/min (20 mL/hr). In the control group (n = 6), saline was administered at a rate of 20 mL/hr iv. BCA was assessed before and 30 min after starting the H-infusion and at 5, 10, 30 and 60 min after commencing the PGE1 or saline infusion. Arterial blood was obtained simultaneously for measurement of plasma concentrations of epinephrine and norepinephrine by gas chromatography mass spectrometry. In the first protocol, PGE1 produced a dose-dependent increase in the percentage of BCA and 10 microg/kg of PGE1 almost fully reversed the H-induced bronchoconstriction. Plasma catecholamines did not change significantly. In the second protocol, continuous infusion of PGE1 produced a time-dependent reversal of H-induced bronchoconstriction (percentage of BCA increased to 80.0+/-9.0% 60 min after the start of PGE1 infusion), whereas saline infusion did not reverse the bronchoconstriction. Plasma catecholamines did not change significantly in either group. Both intravenous bolus and continuous intravenous infusion of PGE1 reversed the H-induced bronchoconstriction. PGE1 may be used safely for patients with the hyperreactive airway and might be useful as a therapeutic agent for these patients.

Relaxant effect of propofol on the airway in dogs

Propofol has been suggested to produce airway relaxant effects in vivo, although the mechanism is unclear. We have evaluated the bronchodilating effect of propofol using a direct visualization method with a superfine fibreoptic bronchoscope. We studied 21 mongrel dogs anaesthetized with pentobarbital 30 mg kg-1 i.v. and pancuronium 0.2 mg kg-1 h-1. The animals were allocated randomly to one of three groups (n = 7 in each): propofol group, atropine-propofol group and histamine-propofol group. The trachea was intubated using a tracheal tube that had a second lumen for insertion of the bronchoscope to monitor continuously bronchial cross-sectional area (BCA). BCA was measured using the NIH Image program. In the propofol group, dogs were given the following doses of propofol at 10-min intervals: 0 (saline), 0.2, 2.0 and 20 mg kg-1 i.v. In the atropine-propofol group, saline, atropine 0.2 mg kg-1 and propofol 20 mg kg-1 were given at 10-min intervals. In the histamine-propofol group, bronchoconstriction was elicited with histamine 10 micrograms kg-1 and 500 micrograms kg-1 h-1 until the end of the experiment. Thirty minutes after the start of infusion of histamine, propofol (0, 0.2, 2.0 and 20 mg kg-1) was administered. Changes in BCA were expressed as percentage of basal area. Histamine decreased BCA by 39.2 (SEM 5.4%). Propofol increased significantly basal and histamine-decreased BCA in a dose-dependent manner by 18.4 (4.5%) and 15.8 (4.9%), respectively after 20 mg kg-1 i.v. However, propofol following atropine i.v. did not increase BCA (129.9 (8.2)% after atropine vs 125.7 (8.9)% after propofol). Therefore, the relaxant effect of propofol may be a result of reduction in vagal tone.

Relaxant effect of magnesium and zinc on histamine-induced bronchoconstriction in dogs.

Magnesium sulfate (MgSO4) has been reported to produce bronchodilation in asthmatic patients. In vitro studies have suggested that divalent cations inhibit L-type voltage-sensitive calcium ion (Ca2+) channels in cardiac and smooth muscles. In this study, we evaluated the in vitro and in vivo effects of magnesium ion (Mg2+) and zinc ion (Zn2+) on the airway contracted by histamine. A university research laboratory. Tracheal smooth muscle from guinea pigs. Mongrel dogs. The tension of isolated guinea pig tracheal strips was measured isometrically with a force displacement transducer. The specimen was contracted with histamine (10 microM). Then, MgSO4 (n = 6), zinc sulfate (ZnSO4, n = 6), or sodium sulfate (Na2SO4, n = 6) was cumulatively added to the organ bath. The bronchial cross-sectional area of mongrel dogs was measured by a direct visualization method demonstrated previously. The dogs were randomly assigned to three groups: group Mg (n = 7), group Zn (n = 7), and group Na (n = 7). Bronchoconstriction was elicited with histamine (10 microg/kg plus 500 microg/kg/hr iv). Thirty minutes after the start of histamine infusion, 0 (saline), 1, 10, and 100 micromol/kg ZnSO4 or 1, 10, 100, and 1000 micromol/kg MgSO4 or Na2SO4 were administered intravenously in group Zn, Mg, or Na, respectively. The bronchial cross-sectional area was assessed before (basal) and 30 mins after the start of histamine infusion and 5 mins after each dose of ZnSO4, MgSO4, or Na2SO4. Arterial blood was also obtained to measure plasma levels of epinephrine and norepinephrine by gas chromatography-mass spectrometry. All data are expressed as mean +/- SEM. The doses of the divalent cations that reversed histamine-induced contraction by 50% were calculated by GraphPad Prism. MgSO4 and ZnSO4 (9.38+/-0.28 and 1.84+/-0.30 mM, respectively) relaxed histamine-contracted tracheal strip in a concentration-dependent manner, whereas Na2SO4 did not. Similarly, the in vivo study showed that MgSO4 and ZnSO4 dose-dependently reversed histamine-induced bronchoconstriction (potency, ZnSO4 > MgSO4), whereas Na2SO4 did not. In groups Mg and Zn, the plasma catecholamine levels also dose-dependently increased except when 1000 micromol/kg MgSO4 was administered. Because the divalent cations tested produced a spasmolytic effect on the contracted airway, infusion of divalent cations might be effective against asthmatic attack. However, high concentrations of these cations produce significant toxicity, so dosage will be an important concern in development of these agents.

I.v. lidocaine worsens histamine-induced bronchoconstriction in dogs

We have assessed the effect of lidocaine (lignocaine) on histamine-induced bronchoconstriction by direct visualization with a superfine fibreoptic bronchoscope. Seven mongrel dogs were anaesthetized with pentobarbital (pentobarbitone) 30 mg kg-1 followed by 2 mg kg-1 h-1 and pancuronium 200 micrograms kg-1 h-1. The trachea was intubated with a tracheal tube containing a second lumen for insertion of a 2.2-mm fibreoptic bronchoscope. This allowed estimation of the bronchial cross-sectional area (BCA) of the third bronchial bifurcation of the right lung. We used NIH image, a public domain image processing and analysis program. Bronchoconstriction was produced with a bolus dose of histamine 10 micrograms kg-1 i.v. followed by continuous infusion of 500 micrograms kg-1 h-1. After 30 min the following i.v. doses of lidocaine were given: lidocaine 0 (saline), 0.01, 0.1, 1.0 and 10 mg kg-1 at 10-min intervals. BCA was assessed 90 s after each dose. Arterial blood sampling was performed for measurement of plasma catecholamines. Lidocaine 1.0 and 10 mg kg-1 significantly reduced histamine-decreased BCA from 69.7 (SEM 4.1)% to 59.8 (7.3)% and 34.3 (6.8)%, respectively. Plasma concentrations of catecholamines decreased significantly after lidocaine 10 mg kg-1 i.v. In addition, there was a significant correlation between percentage decreases in plasma concentrations of epinephrine (adrenaline) and norepinephrine (noradrenaline) and reduction in %BCA (epinephrine-BCA, P < 0.01, r = 0.674; norepinephrine-BCA, P < 0.01, r = 0.510). This study suggests that i.v. lidocaine may exacerbate histamine-induced bronchoconstriction by a sympatholytic effect. This may have therapeutic implications for patients with acute asthma or anaphylactic shock who may become dependent on circulating catecholamines.

Effect of phenylephrine on histamine-induced bronchoconstriction in dogs.

Although an α-adrenoceptor has been suggested to be involved in the mechanism of asthma, the effect of α1-agonist on the airway is still unclear. In this study we evaluated the effect of phenylephrine on the airway with a direct visualization method using a superfine fiberoptic bronchoscope (SFB). Seven mongrel dogs were anesthetized with pentobarbital (30 mg·kg-1 IV) and paralyzed by pancuronium (0.2mg·kg-1·h-1). The trachea was intubated with an endotracheal tube (ID 7 mm) that has a second lumen for insertion of a SFB (OD 2.2 mm) to monitor the bronchial cross-sectional area (BCA) continuously. The tip of a SFB was placed at the level between the second and third bronchial bifurcation. To assess hemodynamics, the direct arterial blood pressure (ABP) and pulmonary arterial pressure (PAP) were monitored via a femoral arterial catheter and Swan-Granz catheter. Bronchoconstriction was elicited by histamine (10 μg·kg-1+ 500 μg·kg-1·h-1_. At 30 min after the histamine was started, saline or phenylephrine (1, 10, and 100μg·kg-1) was given intravenously. The BCA and hemodynamic variables were assessed before (basal) and 30 min after the histamine was started and 5 min after saline and each phenylephrine dose. Histamine reduced BCA by 40.3±6.3%. Phenylephrine at 10 and 100 μg·kg-1 significantly increased the ABP and PAP; and it significantly decreased the BCA, by 6.5±6.9% and 14.2±7.9%, respectively. Plasma epinephrine and norepinephrine were also significantly reduced following phenylephrine 100 μg·kg-1 IV. The dose of phenylephrine that produced vasopressive actions worsened the histamine-induced bronchoconstriction slightly but significantly. Therefore, phenylephrine should be used with caution in asthmatic patients.

Effects of thiopental on airway calibre in dogs: direct visualization method using a superfine fibreoptic bronchoscope

Induction of anaesthesia with thiopental sometimes causes bronchospasm. Although the mechanism by which thiopental induces bronchospasm may involve cholinergic stimulation, direct spastic effect and histamine release, the spastic effects of thiopental have not been comprehensively defined. In this study, we have assessed the effect of thiopental on in vivo airway smooth muscle tone using direct visualization method with a superfine fibreoptic bronchoscope as previously reported. Twenty-one mongrel dogs were anaesthetized with pentobarbital (30 mg kg-1) and paralysed with pancuronium (200 micrograms kg-1 h-1). The trachea was intubated with a tube that had a second lumen for insertion of the bronchoscope (od: 2.2 mm) to continuously measure bronchial cross-sectional area. The tip of the bronchoscope was placed between the second and third bronchial bifurcation of the right lung. The dogs were allocated to three groups of seven: group T, A+T, H+T. In group T, thiopental 0 (saline), 0.1, 1.0 and 10 mg kg-1 was given i.v. In group A+T, saline i.v., 5 min later atropine 0.1 mg kg-1 i.v., and 5 min later thiopental 10 mg kg-1 was administered. In group H+T, bronchoconstriction was produced with histamine 10 micrograms kg-1 i.v. followed by infusion at 500 micrograms kg-1 h-1. Thirty minutes later, thiopental 0, 1.0 and 10 mg kg-1 were given. Arterial blood sampling was performed for measurement of plasma catecholamines and histamine. In group T, thiopental significantly reduced bronchial cross-sectional area (maximally by 28.7 (5.6% at 0.5 min after thiopental 10 mg kg-1), which returned to the baseline in 3 min, while any changes in plasma concentrations of catecholamines and histamine were not observed except norepinephrine level at 1 min following thiopental 10 mg kg-1 i.v. Atropine pretreatment completely prevented thiopental-induced bronchospasm in group A+T. In group H+T, thiopental 10 mg kg-1 transiently but significantly decreases bronchial cross-sectional area. Therefore, the present study indicates that the mechanism of thiopental bronchospasm may result from cholinergic nerve stimulation.

In vivo spasmolytic effect of ketamine and adrenaline on histamine-induced airway constriction. Direct visualization method with a superfine fibreoptic bronchoscope.

Ketamine (K) has been reported to produce bronchodilation in patients suffering from asthma. Although most researchers have used indirect measurements to study the effect of K in vivo, the reliability of these indirect methods are controversial. We have developed a new technique to measure the bronchial cross-sectional area (BCA) in vivo with a superfine fibreoptic bronchoscope (SFB). Employing this method, we evaluated in vivo spasmolytic effect of K and adrenaline (A). Twenty-one mongrel dogs were anaesthetized with pentobarbitone (30 mg.kg-1) and paralyzed with pancuronium (200 micrograms.kg-1.h-1). The trachea was intubated with an endotracheal tube that has a second lumen for insertion of a SFB (OD: 2.2 mm) to measure the BCA continuously. The tip of the SFB was placed between the 2nd and 3rd bronchial bifurcation of the right lung. A videoprinter printed the BCA, which was then measured with NIH Image. Bronchoconstriction was produced with histamine (H: 10 micrograms.kg-1 + 500 micrograms.kg-1.h-1) which was administered until the end of the experiment. The BCA was assessed before and 30 min after the start of H infusion. The dogs were randomly allocated to 3 groups of 7 dogs each. In group K, K (0-10 mg.kg-1) was given i.v., and the BCA was measured 5 min after each K dose. In group A, A (0-0.4 microgram.kg-1) was given i.v., and the BCA was measured 1 min after each A dose. In group A + K, K (1 mg.kg-1 i.v. + 1 mg.kg-1.h-1 i.v.) was given followed, 30 min after, by A i.v. in the same doses as in group A. The BCA was assessed 30 min after the start of K and again 1 min after each A dose. K 10 mg.kg-1 reversed H-induced bronchoconstriction. A subthreshold dose of K significantly potentiated the effect of A, reversing the decrease in BCA by H. We have found that K could reverse the H-induced bronchoconstriction and potentiate the A-induced bronchial relaxation.

Midazolam reverses histamine-induced bronchoconstriction in dogs.

Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.

Measurement of bronchodilatation using a superfine fibreoptic bronchoscope

In this study, we report the development and accuracy of a direct technique to measure airway calibre using a superfine fibreoptic bronchoscope. Ten mongrel dogs were anaesthetized with pentobarbitone and the trachea intubated with a tracheal tube; the small lumen of the tube allowed passage of a superfine fibreoptic bronchoscope (od 2.2 mm). Bronchial cross-sectional area and airway pressure were recorded continuously and dynamic pulmonary compliance and airway resistance calculated. The dogs were allocated to one of two groups. In the first group (six dogs), bronchoconstriction was induced with histamine 10 micrograms kg-1 i.v. and 500 micrograms kg-1 h-1 c.i.v. Thirty minutes later, adrenaline 0-0.4 mg kg-1 was given i.v. Bronchial cross-sectional area, dynamic pulmonary compliance and airway resistance were assessed simultaneously. In the second group, 0.9% saline was given 30 min after placement of the superfine fibreoptic bronchoscope and 10 min later atropine 0.1 microgram kg-1 was administered. In the first group, histamine decreased mean percentage bronchial cross-sectional area by 49.2 (SD 11.5) %, reduced dynamic pulmonary compliance from 32.1 (12.6) to 22.3 (5.2) ml cm H2O-1 and increased airway resistance from 39.1 (11.6) to 57.2 (10.2) cm H2O litre-1 s-1. Adrenaline produced a dose-dependent increase in percentage bronchial cross-sectional area and dynamic pulmonary compliance to 119.4 (31.3)% and 27.4 (5.5) ml cm H2O-1, respectively, and a decrease in airway resistance to 43.9 (7.2) cm H2O litre-1 s-1. There were significant correlations between percentage bronchial cross-sectional area and dynamic pulmonary compliance (r = 0.720, P < 0.0001) and airway resistance (r = 0.727, P < 0.0001). Atropine 0.1 mg kg-1 increased basal bronchial cross-sectional area to 137.5 (16.9) %. These data indicate that adrenaline reversed histamine- and pentobarbitone-induced bronchoconstriction.

In vivo assessment of droperidol-induced bronchial relaxation in dogs using a superfine fibreoptic bronchoscope

Droperidol has been reported to cause bronchodilatation but its mechanism(s) of action is unknown. We have evaluated the spasmolytic effect of droperidol on histamine- and serotonin (5-HT)-induced bronchoconstriction in dogs. Bronchial cross-sectional area was assessed with a superfine fibreoptic bronchoscope. Twenty-eight mongrel dogs were allocated randomly to one of two groups (histamine and 5-HT) to receive either histamine or 5-HT to induce bronchoconstriction. Changes in bronchial cross-sectional area were presented as percentage of basal bronchial cross-sectional area. Continuous i.v. infusion of histamine 500 micrograms kg-1 h-1 or 5-HT 500 micrograms kg-1 h-1 decreased percentage bronchial cross-sectional area by 46.4 (14.3)% or 68.9 (13.7)%, respectively. In both groups, droperidol reversed bronchoconstriction in a dose-dependent manner. In the histamine but not in the 5-HT group, plasma adrenaline and noradrenaline concentrations increased significantly after i.v. droperidol. In addition, propranolol antagonized droperidol-induced relaxation in the histamine but not in the 5-HT group. Our data indicate that the spasmolytic effect of droperidol on canine airway was caused, at least in part, by both catecholamine releases and 5-HT receptor antagonism.

In vivo direct measurement of the bronchodilating effect of sevoflurane using a superfine fiberoptic bronchoscope: Comparison with enflurane and halothane

Although volatile anesthetics have been shown to have spasmolytic effects on constricted airways, most previous studies were performed to assess bronchodilation with indirect methods such as measurement of airway resistance, whose reliability is controversial. As the authors have developed a new direct method using a superfine fiberoptic bronchoscope (SFB) and confirmed the accuracy of this method, this study assessed the spasmolytic effect of sevoflurane (S) as compared with enflurane (E) and halothane (H). Open-labeled, randomized study. The study protocol was approved by the Animal Care Committee in a school of medicine. Twenty-two mongrel dogs. The dogs were anesthetized with pentobarbital, IV, paralyzed with pancuronium, and the lungs were mechanically ventilated. The endotracheal tube had an additional lumen to insert the SFB (outer diameter 2.2 mm). The tip of the SFB was located between a second and third bronchial bifurcation to continuously monitor the bronchial cross-sectional area (BCA) of third or fourth generation bronchi. The BCA was printed out by videoprinter at the end of expiration and was calculated on a Macintosh IIci computer using an NIH (National Institutes of Health) image program. Bronchoconstriction was produced with histamine (HA: 10 micrograms/kg + 500 micrograms/kg/hr). In the first protocol, 4 mongrel dogs were used to assess the accuracy of the new method. BCA was measured 30 and 60 minutes after the placement of the SFB and also 30 and 60 minutes after the start of the histamine (HA) infusion. Arterial blood (4 mL) was collected at 30 and 60 minutes after placement of the SFB to measure the plasma concentration of catecholamines with gas chromatographic mass spectrometry. In the second protocol, 18 dogs were randomly allocated to 3 groups of 6 each: group S, group E, and group H. Thirty minutes after the start of the HA infusion, the dogs subsequently inhaled the following concentrations of S, E, or H for 15 minutes: 0.2, 0.4, 0.8, and 1.6 minimum alveolar concentrations. The BCA was assessed before and 30 minutes after the start of HA and at the end of the inhalation period of each concentration. In the first study, no significant differences in the BCA were found between 30 and 60 minutes after the placement of the SFB and between 30 and 60 minutes after the start of HA. The plasma concentrations of norepinephrine and epinephrine changed from 138 +/- 45 and 162 +/- 18 to 188 +/- 48 and 136 +/- 18 pg/mL, respectively. In the second study, all volatile anesthetics significantly increased the BCA in a dose-dependent manner. There was no significant difference among the three groups. As the BCA did not change in the first study, the tip of the SBF could be well fixed, and the 30-minute interval is long enough for the HA infusion to produce stable bronchoconstriction. The plasma catecholamine concentrations suggest that the pentobarbital anesthesia was deep enough to inhibit the direct irritant effect of the endotracheal tube and the SFB on the airway. This new direct method indicates that S dilates HA-constricted proximal airway with the same potency as E and H.

Gas transport in branched airways during high-frequency ventilation.

A theoretical model of high-frequency ventilation (HFV) is presented based on the physical convective exchange process that occurs due to the irreversibility of gas velocity profiles in oscillatory flow through the bronchial airways. Mass transport during the convective exchange process can be characterized by a convective exchange length, LE, which depends only on the irreversibility of bronchial velocity profiles and can be measured by the experimental technique of photographic flow visualization in bronchial tree models. Using the exchange length and the molecular diffusivity, a simple model of overall bronchial mass transfer is developed. The model allows a prediction of the mean gas concentration profiles along the airways, the site of maximum mass transfer resistance, and overall flow rate of the gas of interest in or out of the lung as functions of the parameters of HFV. The results predicted by the model agree with the limited experimental data available for animals and humans. For normal unassisted ventilation, total bronchial cross-sectional area around the 15th Weibel bronchial generation is predicted to be the single most important parameter in controlling the total gas transport rate along the airways. For the breathing of room air, values of the respiratory quotient around 0.78 are predicted, which are insensitive to VT and f. The model represents a fruitful combination of fluid mechanical theory and experiment with physiologic data to yield new and deeper insight into the operation of the human respiratory system during HFV and normal breathing.

Effect of edema and height on bronchial diameter and shape in excised dog lung

Mechanical interactions among the artery, bronchus, and lung parenchyma cause the bronchus to be pulled from a circular cross-section in such a way that the largest diameter of the bronchus (Db2) lies along a line joining the centers of bronchus and artery. To effect these interactions, the peribronchovascular interstitial space must transmit stresses from the lung parenchyma to the artery and bronchus. To test how interstitial edema affects the interdependence between the artery and the bronchus, we measured orthogonal diameters (Db2, Db1) from tantulum bronchograms as a function of edema formation at a fixed transpulmonary pressure (Ptp). As lobe weight increased to three times normal, Db2/Db1 decreased from 1.08 to 1.0 at a Ptp of 6 and 25 cm H 2O. Cross-sectional area decreased only at a Ptp of 6 cm H 2O. We conclude (1) that peribronchovascular interstitial (Pi) pressure became more uniform with edema present, causing the bronchus to assume a more circular shape, and (2) that it increased, causing bronchial cross-sectional area to decrease at a Ptp of 6 cm H 2O. To determine whether Pi is uniform with height, in a separate group of lungs we measured Db1 as a function of height in two configurations; hilus-dependent, Db1(d) and then inverted or hilus-nondependent, Db1(nd). Db1 was unaffected by lobe inversion at 25, 10, 6 and 4 cm H 2O Ptp. At a Ptp of 2 cm H 2O, the difference Db1(d) - Db1(nd) was positive near the hilus, decreased to zero in the lung periphery, and increased with edema. This bronchial distortion due to lobe inversion was consistent with the effect of gravitational forces on lung parenchyma as modeled by a finite-element analysis, and was opposite to that predicted by a vertical hydrostatic gradient in Pi.

Quantitative studies on the development of the bronchi and bronchial glands of the pig from birth to maturity.

Cross-sectional areas of bronchi and bronchial glands of pigs aged from 1 day to 10 months were measured using image analysis. Growth of the bronchial glands was slow for the first month of life, reached a maximum between 1 and 3 months, and slowed again after 5 months. Mucous gland sizes fell into two groups, one included the apical, cardiac and accessory lobes, the other the diaphragmatic lobes. From birth to maturity the percentage increase in mucous gland area of all lobes was very similar. For the anterior lobes, mucous glands and bronchial lumina grew in direct proportion to each other. Up to 1 month of age the bronchial lumina of the diaphragmatic lobes grew but the glands did not. Later, glands and lumina grew in direct proportion. From birth to maturity the percentage increase in bronchial cross-sectional area was similar for all lobes.