Changes In Pulmonary Mechanics Research Articles

Pulmonary Mechanical Responses to Intravenously Administered Capsaicin in Guinea-pigs: Effect of Peptidase Inhibitors

Summary: In order to examine the role of peptidases in modulating bronchoconstrictor responses to iv administered capsaicin, a potent C-fiber stimulant, we measured changes in pulmonary conductance ( G L ) and dynamic compliance ( C dyn) in anesthetized mechanically ventilated guinea-pigs. Control guinea-pigs, and guinea-pigs treated with the neutral endopeptidase (NEP) inhibitors thiorphan (1.7 mg/kg) or SCH32615 (1 mg/kg), the angiotensin converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), or combinations of NEP and ACE inhibitors, were given increasing doses of capsaicin by rapid iv injection. The doses of capsaicin required to cause a 50% decrease in G L and C dyn (ED 50 G L and ED 50 C dyn respectively) were computed for each animal. None of the peptidase inhibitors, when given alone, had any effect on the changes in pulmonary mechanics induced by capsaicin. However, combined administration of thiorphan and captopril, or SCH32615 and captopril, caused a decrease in ED 50 C dyn for capsaicin, and prolonged the time during which the peak changes in G L induced by capsaicin persisted. These data support the hypothesis that substances whose degradation is inhibited by combined NEP and ACE inhibitors contribute to the bronchoconstriction induced by iv administered capsaicin. This profile of enzymatic degradation is consistent with the tachykinin, substance P.

Cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease.

Severe chronic obstructive pulmonary disease is characterized by limited exercise capacity as a result of changes in pulmonary mechanics, abnormal gas exchange, altered cardiac function, respiratory muscle dysfunction, nutritional factors, and dyspnea. Cardiopulmonary exercise testing is a safe, effective method for objectively studying exercise performance and may be carried out using simple walk tests or more complicated treadmill or cycle-ergometry testing. Indications in patients with chronic obstructive pulmonary disease include defining the etiology of dyspnea, evaluating work disability or impairment, and assessing the response to therapy or the need for supplemental oxygen. It is also indicated in preoperative evaluation and as part of a pulmonary rehabilitation program.

Heat and water exchange in human airways.

The intrathoracic airways of humans play a prominent part in conditioning inspired air. During inspiration the air is warmed and humidified by the movement of heat and water from the mucosa as a direct function of the temperature and vapor pressure gradients that exist. In this process, the mucosa is cooled. During expiration, the gradients are reversed, and heat and water are given back into the airways. At low levels of ventilation, most of the conditioning process takes place in the upper air passages; however, as ventilation rises, more and more of the tracheobronchial tree becomes involved, and incompletely conditioned air penetrates deeply into the distal airways before it is brought to equilibrium with body conditions. It is likely that the heat required to condition the inspired air is derived from the bronchial circulation, but this has not yet been definitely proved. In normal persons, the thermal events associated with the conditioning of inspired air do not produce any changes in pulmonary mechanics. In contrast, in asthmatics, the airway cooling of hyperpnea and the rapid rewarming that develops when hyperpnea is terminated evoke bronchoconstriction.

Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine.

We assessed pulmonary mechanics in six open-chest rabbits (3 young and 3 adult) by the forced oscillation technique between 0.16 and 10.64 Hz. Under control conditions, pulmonary resistance (RL) decreased markedly between 0.16 and 4 Hz, after which it became reasonably constant. Measurements of alveolar pressure from two alveolar capsules in each rabbit showed that the large decrease of RL with increasing frequency below 4 Hz was due to lung tissue rheology and that tissue resistance was close to zero above 4 Hz. Estimates of resistance and elastance, also obtained by fitting tidal ventilation data at 1 Hz to the equation of the linear single-compartment model, gave values for RL motion that were slightly higher than those obtained by forced oscillations at the same frequency, presumably because of the flow dependence of airways resistance. After treatment with increasing doses of aerosolized methacholine, RL and pulmonary elastance between 0.16 and 1.34 Hz progressively increased, as did the point at which the pulmonary reactance crossed zero (the resonant frequency). The alveolar pressure measurements showed the lung to become increasingly inhomogeneously ventilated in all six animals, whereas in the three younger rabbits lobar atelectasis developed at high methacholine concentrations and the alveolar capsules ceased to communicate with the central airways. We conclude that the low-frequency pulmonary impedance of rabbits exhibits the same qualitative features observed in other species and that it is a sensitive indicator of the changes in pulmonary mechanics occurring during bronchoconstriction.

Methacholine-induced bronchoconstriction and phrenic motoneuron activity in dogs

To evaluate the effect of changes in bronchomotor tone on the firing pattern of single phrenic motoneurons, efferent activity of both the C 5 branch phrenic nerve and a single fiber from the contralateral phrenic nerve were studied in dogs anesthetized (chloralose/urethane) and breathing spontaneously (65% O 2). Bronchoconstriction was induced by inhalation of methacholine (MCh) aerosol, which increased total lung resistance, decreased dynamic lung compliance and tidal volume. The rate of rise of phrenic activity was significantly increased by the changes in pulmonary mechanics induced by MCh. Single phrenic motoneurons could be separated into early (EOM) and late (LOM) onset types based on the onset time of firing relative to the beggining of whole phrenic nerve activity. The increased phrenic nerve activity was due primarily to the recruitment of LOMs. The recruitment of LOMs consisted of a shift in the time onset to an earlier portion in inspiration, a longer firing duration, and an increase in the number of spikes per inspiratory cycle. After bilateral cervical vagotomy, all the responses of phrenic nerve to changes in pulmonary mechanics induced by aerosolized MCh were attenuated. These results suggest that phrenic motoneurons activity is modulated by alterations in pulmonary mechanics via a reflex mediated by the vagus nerve and that LOM play an important part in this response.

Nebulized corticosteroid improves pulmonary function and outcome in experimental porcine septicemia

Nebulized beclomethasone dipropionate was administered to six anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (aerosol group). Changes in pulmonary mechanics, gas exchange and hemodynamics during an observation period of 44 h were compared with those in six pigs subjected to the same insults but given no corticosteroid (non-treatment group). Six pigs served as controls, without sepsis or aerosol, but with the same general management (control group). The septic insult induced an acute 3-fold increase in mean pulmonary artery pressure (MPAP) in the aerosol and non-treatment group. MPAP fell to near baseline levels in the aerosol group, but remained significantly higher in the non-treatment group. Mean systemic arterial pressure fell more in the non-treatment than in the aerosol group, reaching its lowest level at 32 h. Pulmonary function was less affected in the aerosol group, with significantly better maintenance of arterial oxygenation, lower venous admixture and superior lung-thorax compliance than in the non-treatment group. Survival was significantly improved in the aerosol group. In this porcine model of septicemia-induced adult respiratory distress syndrome, nebulized corticosteroid thus attenuated the development of respiratory failure.

Pulmonary Mechanics in Preterm Neonates With Respiratory Failure Treated With High-Frequency Oscillatory Ventilation Compared With Conventional Mechanical Ventilation

Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.

Differential effects of oxygen and barotrauma on lung injury in the neonatal piglet

In order to differentiate the effects of hyperoxia and barotrauma in the pathogenesis of acute neonatal lung injury, piglets were either hyperventilated (Paco2, 15-20 torr) for 48 hours with 100% oxygen (Group I), hyperventilated with 21% oxygen (Group II), normally ventilated (Paco2, 40-45 torr) with 100% oxygen (Group III), or normally ventilated with 21% O2 (Group IV) and compared to unventilated controls. Pulmonary function was tested, and biochemical indicators of lung injury were analyzed in tracheo-bronchial aspirates at 0, 24, and 48 hours. Bronchoalveolar lavage fluid was analyzed for surfactant composition and activity at the end of the study. At 48 hours, hyperoxic, hyperventilated piglets had significantly decreased dynamic lung compliance (30%) and increased pulmonary resistance (16%), aspirate cell count (190%), elastase activity (88%), albumin (214%), and total protein (150%) concentration. Qualitative light microscopy showed moderate to severe atelectasis, fibrinous exudate, edema, and inflammation. Normoxic, hyperventilated animals had comparable changes in pulmonary mechanics, but significantly milder cellular, biochemical, and morphologic changes. In hyperoxic, normocarbic animals pulmonary physiologic, cellular, and biochemical variables changed comparably to hyperoxic, hyperventilated animals; the pathologic changes were intermediate between hyperoxic, hyperventilated and normoxic, hyperventilated piglets. Normoxic, normocarbic animals had no significant changes in most variables over 48 hours; on morphologic examination their lungs were similar to unventilated controls and showed only mild edema. Surfactant had normal biophysical activity in all animals. Our results demonstrate that hyperoxia causes more significant physiologic, inflammatory, and histologic changes than barotrauma alone. Future attempts to prevent lung injury in neonates should be directed primarily at oxygen toxicity.

Effects of Protriptyline on Diurnal and Nocturnal Oxygenation in Patients with Chronic Obstructive Pulmonary Disease

To determine the effects of a nonsedating tricyclic antidepressant (protriptyline) on pulmonary function (lung volume, expiratory flow), arterial blood gases, sleep architecture, and sleep-induced breathing abnormalities in patients with chronic obstructive pulmonary disease. A before-and-after trial in which patients, blinded to treatment, were given a placebo for 2 weeks, followed by 2 and 10 weeks of protriptyline treatment. Referral-based pulmonology clinic in a public institution. Sixteen outpatients were enrolled in the trial. Complete results for 11 patients and partial results for 3 patients are presented. Patients were evaluated at baseline, after receiving placebo for 2 weeks, and after 2 and 10 weeks of protriptyline therapy (20 mg/d, taken at bedtime). At baseline, for the whole group, forced expiratory volume in 1 second (FEV1) was 1.0 +/- 0.08 L (mean +/- SE); the partial pressure of O2 in arterial blood (PaO2) was 59 +/- 1.2 mm Hg; and the partial pressure of CO2 in arterial blood (PaCO2) was 48.9 +/- 1.2 mm Hg. These variables remained stable after placebo. Pulmonary function test results were unchanged with protriptyline therapy. Arterial blood gas levels improved with such therapy: PaO2 levels increased by 5.1 +/- 1.4 mm Hg after 2 weeks and 6.7 +/- 2.4 mm Hg after 10 weeks (P less than 0.01); PaCO2 levels decreased by 4.2 +/- 0.9 mm Hg after 2 weeks and 2.2 +/- 1.1 mm Hg after 10 weeks (P less than 0.01). Total sleep times were similar at these visits. The only change in sleep architecture was a significant decrease in rapid eye movement (REM) sleep. The lowest value for the saturation of hemoglobin with O2 in arterial blood (SaO2) seen during sleep was 72.0% +/- 2.0% at baseline. After 2 and 10 weeks of protriptyline therapy, SaO2 values increased by 7.1% +/- 1.6% and 5.0% +/- 2.1%, respectively (P less than 0.01). With protriptyline therapy, the cumulative SaO2 curve, derived from data obtained during sleep, shifted down and to the right. Protriptyline improves diurnal and nocturnal hypoxemia in patients with chronic obstructive pulmonary disease. These changes are not related to changes in pulmonary mechanics.

Vagal cholinergic innervation of the airways in newborn cat and dog

Although several studies have examined the pulmonary response to muscarinic agonists in the newborn, none has addressed the functional capabilities or "maturity" of vagal innervation to airway smooth muscle in the newborn. The purpose of the present study was to provide a quantitative analysis of the ability of vagal excitatory innervation (encompassing the pre- and postganglionic fibers, airway ganglia, and airway smooth muscle) to alter pulmonary mechanics in the newborn. We measured the changes in pulmonary mechanics elicited by electrical stimulation of the vagus nerves in 20 newborn cats and 18 puppies anesthetized with chloralose urethan. Animals were tracheotomized and ventilated (chest open), and the cervical vagus nerves were sectioned and placed on stimulating electrodes. Animals were placed in a flow plethysmograph, and mean inspiratory resistance (RL,I) and dynamic compliance were measured on a breath-by-breath basis. In each animal RL,I increased, dynamic compliance decreased, and heart rate slowed during 10 s of vagal stimulation at frequencies ranging from 2 to 20 pulses/s. At each stimulus frequency there was a spectrum of responses with respect to the percent change in RL,I. At 15 pulses/s there was a fourfold difference in the RL,I response of the most- and least-sensitive animals. In both species, higher stimulus frequencies caused greater increases in RL,I; at 2 pulses/s RL,I increased on average approximately 40%, compared with approximately 250% at 20 pulses/s. The increase in RL,I was similar in the kitten and puppy at stimulus frequencies of 6 and 15 pulses/s but was less in the kitten at 2 pulses/s (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

174 PULMONARY EFFECTS OF CLOSURE OF PATENT DUCTUS ARTERIOSUS (PDA) IN PREMATURE: INFANTS WITH SEVERE RESPIRATORY DISTRESS SYNDROME (RDS)

In preterm infants PDA is generally thought to compromise pulmonary function. Aggressive treatment directed to close the PDA is therefore generally thought to be indicated in these patients. Altogether 8 infants with mean gestational age 26.5 weeks (range 25-30) and mean birth weight 830 g (range 535-1140 g) were studied. Pulmonary mechanics were measured with commercial equipment (PEDS) approx. 24 h. before and 24 as well as 48 h. after treatment (6 surgery, 2 pharmacologic). Data (mean±SEM) are given for lung compliance-CL/kg, pulmonary resistance-R and FiO2(*p <0.05) Closure of PDA resulted in significant improvement in oxygenation. No significant changes in pulmonary mechanics were found.

Effect of single dose surfactant on pulmonary function

Sequential changes in pulmonary mechanics in response to single dose exogenous surfactant instillation were studied in 15 preterm neonates who had hyaline membrane disease (HMD). The infants were part of a larger double-blind national study. Birth weight ranged from 0.88 to 1.55 kg, and gestational age was between 27 to 32 wk. There were six infants in the surfactant group and nine in the placebo group. Pulmonary mechanics were studied before and at 2, 24, 60, and 96 h after surfactant or sham instillation using a pneumotachometer and an esophageal balloon catheter. The variables studied were dynamic compliance (Cdyn), pulmonary resistance, work of breathing, tidal volume, and minute ventilation. Infants in the surfactant group showed an immediate and significant (p less than .05) improvement in gas exchange ratio, decreased mean airway pressure (9.7 +/- 0.9 to 7.9 +/- 0.4 cm H2O) and airway resistance (133 +/- 6.3 to 92 +/- 14.9 cm H2O/L.sec) (p less than .05). Changes in Cdyn were noted only at 24 h after surfactant instillation. In the control group, gradual improvement occurred after the initial deterioration. The findings suggest that the immediate improvement in oxygenation after surfactant instillation is the result of factors other than changes in lung compliance, such as improved ventilation/perfusion and better capillary stability with decreased leakage of fluid into alveoli.

Pulmonary mechanics and energetics of normal, non‐ventilated low birthweight infants

Pulmonary mechanics and energetics were determined in 33 healthy low birthweight infants (less than 1,500 g, 28-34 weeks gestation) who had never received ventilatory support. Tidal volume, dynamic pulmonary compliance, pulmonary resistance, pressure-volume relationships, and tidal flow-volume measurements were obtained by pneumotachography and the esophageal balloon technique. Standardized data collection and software data analysis by least mean squares technique yielded data at 0.5, 1, 2, and 4 weeks postnatally, as a function of gestational age (less than 30, 30-32, and greater than 32 weeks gestation). Relatively stable values were obtained for tidal volume and minute ventilation (normalized for body weight); these were associated with values of peak-to-peak esophageal pressure significantly (P less than 0.001) increasing from 4.4 +/- 0.3 SEM cmH2O at 0.5 weeks to 8.1 +/- 0.8 SEM cmH2O at 4 weeks of age. Dynamic pulmonary compliance ranged from 2.0 to 2.4 mL/cmH2O in the first 4 weeks of life. When normalized for weight, compliance decreased with age, which may suggest a slower pulmonary maturation as compared to increase of body weight. Mean pulmonary resistance decreased from 62.9 cmH2O/L/s at less than 30 weeks gestation to 32.5 cmH2O/L/s at greater than 32 weeks gestation, 0.5 weeks postnatally. Pulmonary resistance peaked at 2 weeks postnatally (P less than 0.05), at all gestational ages, then decreased. Changes in pulmonary mechanics resulted in increasing resistive work of breathing. Our findings suggest a postnatal retardation of pulmonary and airway growth, relative to gestation maturation. These data can provide an objective base of comparison for data in sick, low birthweight neonates.

Pharmacological profile of MDL 26,024GO: a novel antiasthmatic agent.

MDL 26,024GO was shown to be an orally absorbed mediator release inhibitor in the rat PCA and PPA tests. In addition, the compound was shown to both elicit and inhibit elicitation of the Bezold-Jarisch reflex in the dog. MDL 26,024GO also significantly reduced Ascaris-induced changes in pulmonary mechanics in cynomolgus monkeys. The compound inhibited both early and late phase antigen induced-changes in Ascaris-sensitive sheep, as well as the increased airway hyperreactivity which normally follows antigen challenge. These results suggest the compound may have therapeutic potential in the treatment of asthma.

Changes in Pulmonary Mechanics After the Administration of Surfactant to Infants With Respiratory Distress Syndrome

Davis, J. M.; Veness-Meehan, K.; Notter, R. H.; Bhutani, V. K.; Kendig, J. W.; Shapiro, D. L. Author Information

Changes in Pulmonary Mechanics After the Administration of Surfactant to Infants with Respiratory Distress Syndrome

We assessed pulmonary mechanics in 35 premature infants with respiratory distress syndrome just before and one hour after the administration of 90 mg of surfactant to each infant. Transpulmonary pressure was measured between the airway opening and an esophageal balloon with use of a differential transducer, and flow rates were measured by a pneumotachometer. Values for pulmonary mechanics were then calculated by microcomputer processing. The administration of surfactant produced a large decrease (56 percent) in the mean (+/- SEM) ratio of alveolar to arterial oxygen, from 7.1 +/- 0.5 to 3.1 +/- 0.2 (P less than 0.0001)--a change that indicates improvement in gas exchange. Associated changes in pulmonary mechanics were not demonstrable when 10 of the infants were studied during continuous mechanical ventilation. However, in the 25 infants examined during spontaneous breathing with continuous positive airway pressures (identical airway pressures before and after treatment), large and consistent improvements in pulmonary mechanics were found after the administration of surfactant. Tidal volume increased by 32 percent (P less than 0.03), minute ventilation by 38 percent (P less than 0.02), dynamic compliance by 29 percent (P less than 0.004), and inspiratory flow rates by 54 percent (P less than 0.01). We conclude that significant improvement in pulmonary mechanics results from surfactant-replacement therapy for respiratory distress syndrome, but that these mechanical changes are apparent only during spontaneous respiration and can be masked if measurements are made during mechanical ventilation.

Prevention and reversal of aerosol LTD4-induced changes in guinea pig pulmonary mechanics by Wy-48252, an orally active LTD4/E4 receptor antagonist.

Anesthetized male albino guinea pigs were prepared for recording changes in the pulmonary mechanics parameters, dynamic compliance (Cdyn) and airway conductance (Gaw). Two aerosol leukotriene D4 (LTD4) challenges (0.125 microgram/ml, 3-7 breaths, 1 h apart) were administered via an ultrasonic nebulizer to each animal and, produced reductions in Cdyn that were approximately 60% of those of Gaw. Intraduodenal administration of the LTD4/E4 receptor antagonists Wy-48252 (30 min), Wy-45911 and Ly-171883 (15 min) produced dose-related inhibition of the second LTD4 challenge. From the data, ID50 values were calculated and, Wy-48252 was 8- to 17-fold more potent (mg/kg) than Wy-45911 or Ly-171883. Responses to histamine were not altered by the antagonists. In separate experiments, Wy-48252 (0.3 and 1 mg/kg i.v.) rapidly reversed aerosol LTD4-induced decreases of Cdyn and Gaw, but did not reverse pulmonary mechanics decreases produced by prostaglandin F2 alpha. The results indicate that systemically administered LTD4 receptor antagonists can both prevent and reverse bronchoconstriction produced by aerosol LTD4 in the guinea pig.

Sequential changes in pulmonary mechanics in the very low birth weight (≤1000 grams) infant

Pulmonary function tests were performed on 36 very low birth weight neonates (birth weight less than or equal to 1000 gm, gestational age less than or equal to 30 weeks, appropriate size for gestational age) from birth until 8 weeks of age. Tidal airflow was measured by means of a pneumotachygraph, and the transpulmonary pressure changes were determined by the esophageal balloon technique. Pulmonary mechanics and energetics were calculated by the least mean square analysis technique at 1/2, 1, 2, 4, 6, and 8 weeks of age. Compliance was lowest at 2 weeks and subsequently increased linearly (at approximately 0.1 ml/cm H2O/wk). When compliance was based on body weight, however, no change was noted with advancing age. Resistance was greatest at 2 weeks and subsequently decreased. The infants maintained a normal minute ventilation with a slightly increased resistive work of breathing. Despite our ability to wean 53% of the infants to room air by 8 weeks, none of them had pulmonary mechanics considered normal for term infants. Infants with and without bronchopulmonary dysplasia (BPD) had similar patterns of pulmonary development. At 8 weeks of age, the pulmonary mechanics in infants with BPD who had been weaned to room air were comparable to those in infants without BPD, an observation that calls into question the rationale for defining BPD at 4 weeks in this population. These data suggest that such pulmonary function profiles provide evidence of persistent lung parenchymal abnormalities.

Changes in pulmonary mechanics after the administration of surfactant to infants with respiratory distress syndrome.

We assessed pulmonary mechanics in 35 premature infants with respiratory distress syndrome just before and one hour after the administration of 90 mg of surfactant to each infant. Transpulmonary pressure was measured between the airway opening and an esophageal balloon with use of a differential transducer, and flow rates were measured by a pneumotachometer. Values for pulmonary mechanics were then calculated by microcomputer processing. The administration of surfactant produced a large decrease (56 percent) in the mean (+/- SEM) ratio of alveolar to arterial oxygen, from 7.1 +/- 0.5 to 3.1 +/- 0.2 (P less than 0.0001)--a change that indicates improvement in gas exchange. Associated changes in pulmonary mechanics were not demonstrable when 10 of the infants were studied during continuous mechanical ventilation. However, in the 25 infants examined during spontaneous breathing with continuous positive airway pressures (identical airway pressures before and after treatment), large and consistent improvements in pulmonary mechanics were found after the administration of surfactant. Tidal volume increased by 32 percent (P less than 0.03), minute ventilation by 38 percent (P less than 0.02), dynamic compliance by 29 percent (P less than 0.004), and inspiratory flow rates by 54 percent (P less than 0.01). We conclude that significant improvement in pulmonary mechanics results from surfactant-replacement therapy for respiratory distress syndrome, but that these mechanical changes are apparent only during spontaneous respiration and can be masked if measurements are made during mechanical ventilation.

Bronchoprotective and bronchodilator activity of anaritide (human atrial natriuretic factor [102–126]) infusion in the anesthetized guinea pig

The present study examined the bronchoprotective and bronchodilator efficacy of infused human atrial natriuretic factor [102-126] (Anaritide) in the guinea pig. Anesthetized and paralyzed male guinea pigs, ventilated via a tracheal cannula, were placed in a plethysmograph for measurement of agonist-induced changes in pulmonary mechanics. Reductions in dynamic compliance of the lung and airway conductance were produced either by 3 to 7 tidal volume breaths of leukotriene D4 (0.125 micrograms/ml) delivered through an ultrasonic nebulizer or by intravenous histamine (2.8 +/- 0.2 micrograms/kg). Infusion of Anaritide (1 microgram/kg/min), before evoking bronchoconstriction with either LTD4 or histamine, produced a significant protection against bronchoconstriction produced by aerosol LTD4, but not against histamine-induced bronchoconstriction of similar magnitude. In other experiments, Anaritide infusion (0.5-2 micrograms/kg/min) also rapidly reversed a stable LTD4-induced decrease in airway conductance, but did not produce a similar reversal of the decrease in dynamic compliance. The data provide evidence that intravenous Anaritide exerts both bronchoprotective and bronchodilator effects against LTD4-induced bronchospasm.