Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs

BACKGROUND: Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension. METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines. RESULTS: 5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v.. CONCLUSION: In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.     

Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs

BACKGROUND: We have previously found that agents increasing intracellular cAMP levels of smooth muscles, such as PDE3 inhibitors, aminophylline and prostaglandin E1, produce both bronchodilation and pulmonary vasodilation in serotonin-induced pulmonary hypertension and bronchoconstriction models. In the present study we have simultaneously evaluated the spasmolytic effects of colforsin daropate, a novel forskolin derivative, on serotonin-induced pulmonary hypertension and bronchoconstriction. METHODS: Ten mongrel dogs were anesthetized with pentobarbital. The pulmonary hypertension and bronchoconstriction were elicited with serotonin (10 microg/kg + 1 mg x kg(-1) x h(-1)) and assessed as percentage changes in pulmonary vascular resistance (PVR) and bronchial cross-sectional area (BCA) (basal = 100%). Initially, the relaxant effects of colforsin daropate (0-300 microg/kg) were determined. The PVR and BCA were assessed before and 30 min after serotonin infusion began and 5 min after each dose of colforsin daropate. To determine whether colforsin daropate-induced relaxation is independent of plasma catecholamine, propranolol 0.4 mg/kg was given following colforsin daropate 300 microg/kg i.v. RESULTS: Colforsin daropate reversed both pulmonary hypertension and bronchoconstriction dose-dependently: -logED50 (95% confidence intervals, mean ED50) for pulmonary hypertension and bronchoconstriction 5.44 (5.08-5.80, 3.6 microg/kg) and 4.90 (4.06-5.20, 12.5 microg/kg), respectively. However, colforsin daropate (>or= 30 microg/kg) produced a more pronounced systemic than pulmonary vasodilation. Although colforsin daropate (>or= 30 microg/kg) significantly increased plasma catecholamines, propranolol did not reverse the relaxant effects. CONCLUSIONS: Colforsin daropate may attenuate bronchoconstriction and pulmonary hypertension. In addition, as beta-blockade did not change the attenuation, the relaxant effects may be independent of plasma catecholamines.     

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs

In this study, we simultaneously evaluated the spasmolytic effectsof prostaglandin E₁ (PGE₁) on serotonin-induced bronchoconstrictionand pulmonary hypertension. Eleven mongrel dogs (8–12kg) anaesthetized with pentobarbital were assigned to two groups:saline (n=4) and PGE₁ (n=7). Bronchoconstriction and pulmonaryhypertension were elicited with serotonin 10 µg kg^–1+ 1 mg kg^–1 h^–1 and assessed as the percentage changein bronchial cross-sectional area (BCA) measured by bronchoscopyand pulmonary vascular resistance (PVR), respectively. Thirtyminutes after starting the serotonin infusion, saline or PGE₁0 (saline), 0.01, 0.1, 1.0 or 10 µg kg^–1 i.v. wasgiven. %BCA and %PVR (basal=100%) were assessed before and 30min after serotonin, and 30 and 60 min after saline (salinegroup) or 5 min after each dose of PGE₁ (PGE₁ group). In thesaline group, pulmonary hypertension and bronchoconstrictionwere stable. In the PGE₁ group, PGE₁ at     

A comparison of the spasmolytic effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction with or without beta-blockade in dogs

In the present study in dogs, we compared with aminophylline the spasmolytic effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin-induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induced with serotonin: 10 microg/kg + 1 mg x kg(-1) x h(-1), and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0-1000 microg/kg) and aminophylline (n = 8: 0-100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminophylline dose-dependently attenuated both PH and bronchoconstriction (olprinone > aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37+/- 0.35[4.24 microg/kg] vs. 1.60+/-0.23[25.4 mg/kg] and 4.06+/-0.12[87.8 microg/kg] vs. 1.51+/-0.21[30.6 mg/kg], respectively). In addition, olprinone produced more potent pulmonary vasodilation than bronchodilation while aminophylline was equipotent. In addition, there was a significant increase in plasma catecholamines after olprinone (> or =100 microg/kg) and aminophylline (> or =10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measured. Therefore, the spasmolytic effects of olprinone are independent of plasma catecholamines, while the bronchodilating effect of aminophylline may partially involve increased levels of circulating catecholamines.     

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs

Background. Thiopental sometimes causes bronchospasm duringinduction of anaesthesia. In addition, we have reported previouslythat thiopental produced transient bronchospasm, which was blockedby atropine pretreatment, and worsened histamine-induced bronchoconstrictionin dogs. Previous in vitro reports suggest that synthesis ofcontractile cyclooxygenase products, such as thromboxane A₂,may be involved in the mechanism of bronchospasm. However, thein vivo spastic effects have not been defined comprehensively. Methods. Twenty-seven mongrel dogs were anaesthetized with pentobarbital.Bronchoconstriction was elicited with methacholine (0.5 µg kg^–1+5.0µg kg^–1 min^–1; Mch group, n=7) orserotonin (10 µg kg^–1+1 mg kg^–1 h^–1;5HT group, n=20), and assessed as percentage changes in bronchialcross-sectional area (BCA, basal=100%) using a bronchoscope.In the 5HT group, dogs were subdivided into four groups of fiveeach: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HTgroups, 30 min before serotonin infusion dogs were given salineand indomethacin respectively at 5 mg kg^–1 i.v. Inall groups, 30 min after bronchoconstrictor infusion started,dogs were given thiopental at doses between 0 (saline) and 20mg kg^–1. In the 5HT-S and 5HT-A groups, dogs weregiven saline or atropine 0.2 mg kg^–1 i.v. 5 min afterthiopental 20 mg kg^–1. Results. Methacholine and serotonin reduced BCA by about 50and 40% respectively. Thiopental 20 mg kg^–1 increasedand decreased BCA by about 20 and 10% in the Mch and 5HT groupsrespectively. Indomethacin and atropine did not attenuate thepotentiation of serotonin bronchoconstriction produced by thiopental. Conclusion. The present study indicates that thiopental mayattenuate or worsen bronchoconstriction induced by muscarinicor serotonin receptor stimulation, respectively. The synthesisof contractile cyclooxygenase products and cholinergic stimulationmay not be involved in the contractile effect of thiopentalon serotonin bronchoconstriction. Br J Anaesth 2003; 91: 379–84     

Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs

BACKGROUND: Clinical use of high dose beta-blocker therapy is limited by excessive negative inotropic effects. Previous studies suggest that milrinone may be of utility in limiting the inotropic but not the chronotropic effects of beta blockers. We examined the hemodynamic effects of co-administration of a new potent selective beta(1) blocker, landiolol, and milrinone in halothane-anesthetized dogs. METHODS: Eighteen adult mongrel dogs were anesthetized with 1.2 MAC halothane. Hemodynamic measurements were made at baseline, 30 min after starting the milrinone (0.5 micro g x kg(-1) x min(-1)) or normal saline infusion (n = 9 in each), then 30 min after each change in the dose of landiolol infusion. The tested doses of landiolol were 10, 100, and 1000 micro g x kg(-1) x min(-1). RESULTS: Landiolol (>/= 10 micro g x kg(-1) x min(-1)) has significant and comparable negative chronotropic effects in both groups of dogs. While it also has significant negative inotropic effects in both groups, such effects are significantly attenuated in the dogs treated with milrinone. CONCLUSION: Milrinone is effective to attenuate the negative inotropic effects of landiolol in halothane-anesthetized dogs.     

Effects of pulmonary allotransplantation in dogs with microembolic pulmonary hypertension

Glass bead embolization was employed in 42 dogs to produce pulmonary hypertension prior to allotransplantation of a normal left lung. There was an early mortality of 48% after beads were administered, but survivors showed pulmonary hypertension for three to four weeks and variable effects on pulmonary function. Of 17 surviving animals that received unselected normal canine left lungs, 12 lived longer than 48 hours with evidence of progressive hemodynamic benefit in comparison with nonoperated controls. Surviving animals showed decreases in mean pulmonary artery pressure and pulmonary vascular resistance and increased resting cardiac output. Respiratory function changes induced by embolization, including hypoxia, elevated dead space/tidal volume ratios, and increased alveolar-arterial oxygen tension gradients, were not improved consistently by allotransplantation during the period of observation.     

Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in chronically instrumented dogs

BACKGROUND: The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state. METHODS: Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators. RESULTS: Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation. CONCLUSION: These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.     

Midazolam reverses histamine-induced bronchoconstriction in dogs

Purpose

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.

Methods

After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg · kg^?1 pentobarbitoneiv, and were paralysed with 200 μg · 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 nght bronchus. A videopnnter printed the BCA which was then measured with a NIH Image program. Bronchoconstnction was produced with histamine (H) 10 μg · kg^?1 followed by 500 μg · kg^?1 · hr^?1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg · kg^?1 midazolam and 25 μg · 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 flumazeniliv. At the same time, arterial blood was sampled for plasma catecholamine measurement.

Results

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.

Conclusion

Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.     

急性颅内压增高时肺动静脉分流的意义

目的 探讨颅内压增高对呼吸功能的影响。方法 16条犬分为高颅压组和对照组。高颅压组升高颅内压至 8 kPa(1 kPa=7.5 mm Hg),维持 6 h。两组均行肺动脉插管,动态测量肺分流量。结果 颅内压增高后肺动脉压、肺血管阻力指数、肺泡动脉氧分压差显著增加;肺动静脉分流率(Qs/Qt)迅速从(9.70±4.83)％增加到(21.80±6.89)％(P<0.01)。呼吸抑制、肺不张、肺水肿、肺部感染、肺血流动力变化共同参与颅内压增高后的肺分流增加。结论 肺分流率是颅内压增高后呼吸功能不全的重要指标。     

Effect of phenylephrine on histamine-induced bronchoconstriction in dogs

Purpose 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). Methods 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. Results 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. Conclusion 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.     

Small-dose inhaled nitric oxide attenuates hemodynamic changes after pulmonary air embolism in dogs.

Inhaled nitric oxide (NO) has been used to treat pulmonary hypertension. Experimental studies have suggested therapeutic effects of NO after pulmonary microembolism. We evaluated the protective effects of NO in dogs during a pulmonary air embolism (PAE). NO (3 ppm) was administered to six anesthetized mongrel dogs (NO group) but not to the seven dogs in the control group. After 20 min, each dog received a venous air injection of 2.5 mL/kg. Hemodynamic evaluation was performed, and blood samples were drawn for blood gas analysis before and after NO inhalation and 5-60 min after the PAE. Both arterial blood pressure and cardiac output were decreased in the control group for >15 min after PAE, whereas NO-treated animals showed only transient hypotension. NO attenuated the pulmonary hypertension after PAE, as demonstrated by small (P < 0.05) increases in pulmonary artery pressure and pulmonary vascular resistance index in NO-treated animals (90% and 135%, respectively) compared with the controls (196% and 282%, respectively). These hemodynamic effects of NO were associated with higher mixed venous O2 tensions and saturations in the NO group compared with the controls. We conclude that small-dose NO (3 ppm) attenuated the hemodynamic changes induced by PAE in dogs. This protective effect of NO on hemodynamics is not accompanied by improvement in pulmonary oxygenation in this setting. IMPLICATIONS: In this study, we evaluated the protective effects of inhaled nitric oxide in a pulmonary air embolism setting. Nitric oxide attenuated the hemodynamic changes induced by pulmonary air embolism without improving pulmonary oxygenation.     

Effects of inhaled nitric oxide on platelet-activating factor-induced pulmonary hypertension in dogs

Background: Platelet-activating factor (PAF), a lipid mediator released during endotoxin shock, induces pulmonary hypertension, systemic hypotension and cardiac dysfunction. In this study, we compared the effect of inhaled nitric oxide (NO) on PAF-induced pulmonary hypertension and NO metabolism with that on pulmonary hypertension induced by a stable thromboxane A₂ mimetic, U46619. Since PAF-induced hypotension might be mediated by NO, the effect of inhaled NO combined with an intravenously administered NO synthase inhibitor, N^G-nitro-L-arginine (L-NNA), on PAF-induced hemodynamic change was also investigated. Methods: In a total of 28 beagles anesthetized with pentobarbital the following substances were intravenously administered: PAF 0.56±0.30 μg·kg^-1·min^-1 (group PAF), L-NNA 10 mg·kg^-1+ PAF 0.04±0.03 μg·kg^-1· min^-1 (group L-NNA+ PAF), U46619 0.60±0.11 μg·kg^-1·min^-1 (group U46619) or L-NNA 10 mg·kg^-1+ U46619 0.61±0.23 μg·kg^-1· min^-1 (group L-NNA+U46619) to obtain a mean pulmonary arterial pressure (MPAP) of 25 mmHg. Nitric oxide was then inhaled at 5, 10, 20 and 40 ppm for 15 min at 15-min intervals in the order of increasing concentration. An additional 7 dogs (control group) inhaled NO at normal MPAP (17 mmHg). Hemodynamic and respiratory parameters, NOHb, NO₂^-+NO₃^-, and MetHb levels in blood were measured before and during NO administration. Results: In the control group, hemodynamic and respiratory values did not change significantly during NO administration. In group PAF, NO significantly reversed the PAF-induced pulmonary hypertension. PAF induced a marked systemic hypotension and cardiac output reduction, but these changes were not affected by inhalation of NO. L-NNA pretreatment markedly decreased the dose of PAF required to maintain a MPAP of 25 mmHg, and abolished the PAF-induced hypotension. In group L-NNA+PAF, the diminishing effect of inhaled NO on pulmonary vascular resistance (PVR) was significantly greater than that in group PAF. U46619 induced pulmonary hypertension and increases in blood pressure, intrapulmonary shunt and peak airway pressure. L-NNA pretreatment did not change the dose of U46619 required to maintain a MPAP of 25 mmHg. The effects of inhaled NO on PVR decrease were similar in groups U46619 and L-NNA+U46619. No NOHb was detected in any group. NO₂^-+NO₃^- concentration increased during NO administrations. There were no significant differences in NO₂^-+NO₃^-concentration among groups. Conclusions: Inhaled NO at the dose of 5–40 ppm effectively reversed PAF-induced pulmonary hypertension, especially following pretreatment with L-NNA. Inhaled NO did not affect PAF-induced hypotension or cardiac dysfunction. These findings indicate that low concentrations of inhaled NO may be useful in reversing pulmonary hypertension in the endotoxemia where PAF may be one mediator.     

ProT-α gene transfer attenuates cardiopulmonary remedying and mortality in a flow-induced pulmonary hypertension rat model

1. Download : Download high-res image (229KB)
2. Download : Download full-size image

     

Milrinone decreases both pulmonary arterial and venous resistances in the hypoxic dog

We have studied the effect of milrinone on pulmonary vascular resistance (PVR) in dogs with hypoxic pulmonary vasoconstriction (HPV). Using a pulmonary arterial occlusion method, we measured effective pulmonary capillary pressure (Pcap) by which total PVR was partitioned into arterial (PVRa) and venous (PVRv) components. Hypoxic ventilation (FIO2 = 0.11-0.13) produced significant increases in mean pulmonary arterial pressure (PAP) and Pcap (P < 0.01) associated with increases in PVRa and PVRv (P < 0.01). During the hypoxic period, milrinone significantly decreased mean PAP and Pcap (P < 0.01), reflected in decreases in PVRa and PVRv (P < 0.01). The longitudinal distribution of PVR (PVRa/PVRv) remained unchanged throughout the experiment, indicating that HPV occurred equally in the arterial and venous segments and that milrinone-induced vasodilatation occurred equally in both segments. During hypoxia, milrinone did not produce an increase in cardiac output or a decrease in PaO2. Milrinone also produced significant decreases in mean systemic arterial pressure (P < 0.01) and systemic vascular resistance (P < 0.05) to a similar extent to the decreases in mean PAP and PVR, suggesting no selective dilating effect of milrinone on the pulmonary vasculature. These results indicate that in HPV, milrinone decreased the vascular tone of both pulmonary arterial and venous segments without increasing cardiac work or impairing pulmonary oxygenation. This suggests a potential for use in patients suffering from hypoxic pulmonary hypertension.      

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.