The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB neuropsychological test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effects on CANTAB measures were detected. We conclude that the effect of antipsychotics on LI is both modality and pharmacologically dependent and that further research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether there are important differences between them.

An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors.

Since the original work of by Hering and Breuer in 1868 numerous studies have demonstrated that slowly adapting pulmonary stretch receptors (SARs) are the lung vagal afferents responsible for eliciting the reflexes evoked by moderate lung inflation. SARs play a role in controlling breathing pattern, airway smooth muscle tone, systemic vascular resistance and heart rate. Both anatomical and physiological studies support the contention that SARs, by their close association with airway smooth muscle, continuously sense the tension within the myoelastic components of the airways caused by lung inflation, smooth muscle contraction and/or tethering of small intrapulmonary airways to the lung parenchyma. In addition, intrapulmonary SAR discharge activity is sensitive to changes in P(CO2) within the physiological range. Despite this extensive characterization of SARs, their role in determining breathing pattern and airway tone in individuals with respiratory diseases is only recently being appreciated.

Antisaccade and smooth pursuit eye movements in healthy subjects receiving sertraline and lorazepam.

Patients suffering from some psychiatric and neurological disorders demonstrate abnormally high levels of saccadic distractibility when carrying out the antisaccade task. This has been particularly thoroughly demonstrated in patients with schizophrenia. A large body of evidence has been accumulated from studies of patients which suggests that such eye movement abnormalities may arise from frontal lobe dysfunction. The psychopharmacology of saccadic distractibility is less well understood, but is relevant both to interpreting patient studies and to establishing the neurological basis of their findings. Twenty healthy subjects received lorazepam 0.5 mg, 1 mg and 2 mg, sertraline 50 mg and placebo in a balanced, repeated measures study design. Antisaccade, no-saccade, visually guided saccade and smooth pursuit tasks were carried out and the effects of practice and drugs measured. Lorazepam increased direction errors in the antisaccade and no-saccade tasks in a dose-dependent manner. Sertraline had no effect on these measures. Correlation showed a statistically significant, but rather weak, association between direction errors and smooth pursuit measures. Practice was shown to have a powerful effect on antisaccade direction errors. This study supports our previous work by confirming that lorazepam reliably worsens saccadic distractibility, in contrast to other psychotropic drugs such as sertraline and chlorpromazine. Our results also suggest that other studies in this field, particularly those using parallel groups design, should take account of practice effects.

Interaction of vagal lung afferents with inhalation of histamine aerosol in anesthetized dogs.

In seven alpha-chloralose anesthetized dogs we examined the contribution of lung afferents to the rapid, shallow breathing induced by inhalation of 10 breaths of histamine aerosol. In four spontaneously breathing dogs, the inhalation of histamine caused an increased respiratory frequency, decreased tidal volume, and decreased dynamic lung compliance. Selective blockade of pulmonary C-fibers abolished a reflex-induced increase in respiratory frequency but did not significantly affect the reductions in tidal volume or lung compliance. Terbutaline treatment in combination with C-fiber blockade abolished the reductions in tidal volume and lung compliance induced by histamine. In three separate alpha-chloralose anesthetized, open-chest, mechanically ventilated dogs, we recorded an increase in the inspiratory activity of rapidly adapting pulmonary stretch receptors (RARs) induced by the inhalation of histamine aerosol. Selective C-fiber blockade abolished histamine-induced increases in RAR activity while only partially attenuating reductions in lung compliance. We conclude that the increase in RAR activity induced by histamine depends on intact C-fibers and not on a direct effect of histamine on RARs or an indirect effect of histamine reducing lung compliance. In addition, our data illustrate the multiple interactions that occur between the various vagal afferents and their roles in the reflexes induced by histamine inhalation.

Vertical fixation disparity curve and the effects of vergence training in a normal young adult population.

BACKGROUND: The vertical forced vergence fixation disparity (VFD) curve represents the amount of vertical fixation disparity, the steady-state vertical bifixation error of the eyes, at various levels of vertical vergence demand. The main aim of the present study was to examine the effects of vertical vergence training on the slope of the VFD curve in a normal, young adult population. METHODS: Forty-five subjects with normal vision and binocular function underwent vertical vergence training for 1 week. The training was done using a vertical prism bar, and the vertical fixation disparity was measured using the Disparometer. RESULTS: The mean slope of the VFD curve in a normal, young adult population was 1.103 min arc/delta. The slope of the VFD curve decreased significantly after the training and remained flattened for at least 3 months. There was no evidence to support the idea that the decrease in the VFD slope was related to the increase of vertical fusional amplitude. CONCLUSIONS: Vertical prism bar training provided a long-term effect, both increasing the vertical fusional amplitude and flattening the slope of the VFD curve. The decrease in the slope of the VFD curve was thought to be independent of the increase of vertical fusional amplitude.

The effect of sleep deprivation on memory and psychomotor function in healthy volunteers.

Benzodiazepines and other psychotropic drugs have been implicated in the production of memory deficits. The mechanism is unclear, but both a distinct pharmacological action and a non-specific sedative effect have been suggested as being causal or contributory. These two postulated mechanisms of action may be examined separately by using sleep deprivation as a method of non-pharmacological sedation. We measured psychomotor and memory functions in eight sleep-deprived healthy volunteers and eight controls. There was both subjective and objective evidence of sedation, but memory function was not affected. These findings support the view that the effect on memory of psychotropic drugs is principally caused by a direct amnestic effect rather than by drug-induced sedation. Copyright 2000 John Wiley & Sons, Ltd.

Breathing pattern response and epithelial labeling in ozone-induced airway injury in neutrophil-depleted rats.

To test the hypothesis that neutrophils enhance the repair of ozone (O3)-injured airway epithelium, we investigated breathing pattern responses and airway epithelial injury and repair in rats depleted of neutrophils using rabbit antirat neutrophil serum (ANS) and control rats treated with normal rabbit serum (NRS). Thirty-seven Wistar rats were exposed to O3 (1 ppm) or filtered air (FA) for 8 h followed by 8 h in FA. O3-exposed NRS- and ANS-treated rats showed similar progressive decreases in tidal volume and increase in breathing frequency, with maximal changes occurring at 8 h of exposure, whereas FA-exposed rats showed no significant changes. O3-exposed ANS-treated rats showed more epithelial necrosis in the nasal cavity, bronchi, and distal airways than did O3-exposed NRS-treated rats. Incorporation of 5-bromo-2-deoxyuridine (BrdU), a measure of cellular proliferation, was assessed using an optical disector to count BrdU- labeled terminal bronchiolar epithelial cells. O3-exposed ANS-treated rats had significantly less BrdU- labeled epithelial cells than did O3-exposed NRS-treated rats. We conclude that neutrophils contribute to the repair process by enhancing the proliferation of O3-injured airway epithelial cells.

Capsaicin-sensitive C-fiber-mediated protective responses in ozone inhalation in rats.

To assess the role of lung sensory C fibers during and after inhalation of 1 part/million ozone for 8 h, we compared breathing pattern responses and epithelial injury-inflammation-repair in rats depleted of C fibers by systemic administration of capsaicin as neonates and in vehicle-treated control animals. Capsaicin-treated rats did not develop ozone-induced rapid, shallow breathing. Capsaicin-treated rats showed more severe necrosis in the nasal cavity and greater inflammation throughout the respiratory tract than did control rats exposed to ozone. Incorporation of 5-bromo-2'-deoxyuridine (a marker of DNA synthesis associated with proliferation) into terminal bronchiolar epithelial cells was not significantly affected by capsaicin treatment in rats exposed to ozone. However, when normalized to the degree of epithelial necrosis present in each rat studied, there was less 5-bromo-2'-deoxyuridine labeling in the terminal bronchioles of capsaicin-treated rats. These observations suggest that the ozone-induced release of neuropeptides does not measurably contribute to airway inflammation but may play a role in modulating basal and reparative airway epithelial cell proliferation.

The effects of chlorpromazine and lorazepam on abnormal antisaccade and no-saccade distractibility.

BACKGROUND: Abnormally high levels of saccadic distractibility have been demonstrated to occur in patients with schizophrenia. Converging evidence implicates frontal cortical dysfunction as a mechanism; however, much of the neuropharmacology of saccadic distractibility has not yet been established. METHODS: We measured antisaccade, no-saccade, and visually guided saccade components in healthy subjects following single doses of lorazepam 2 mg, chlorpromazine 50-100 mg, and placebo. Visual analogue rating scales (VARS) provided a subjective measure of sedation. RESULTS: Lorazepam, but not chlorpromazine, was shown to cause an increase in saccadic distractibility in both the antisaccade and no-saccade tasks. Peak visually guided saccade velocity was decreased by lorazepam and chlorpromazine in a dose-dependent manner, with corresponding changes seen in VARS. Lorazepam, unexpectedly, did not affect peak antisaccade velocity. The background level of antisaccade directional errors was 6.43%, which is relatively low compared to control groups in patient studies. CONCLUSIONS: These results support the view that abnormal saccadic distractibility in patients with schizophrenia is not due to an acute effect of antipsychotic medication. The use of benzodiazepines and the level of task practice are highlighted as possible confounding variables in patient studies. The implications of these results for the current neuropathological theories of abnormal saccadic distractibility are discussed.

Control of ventilation during lung volume changes and permissive hypercapnia in dogs.

We investigated the effect changes in end-expiratory lung volume (EEVL) had on the response to progressive hypercapnia (CO2-response curve) in eight open-chest, anesthetized dogs, in order to clarify the role that vagal lung mechanoreceptors have in altered respiratory drive during permissive hypercapnia. The dogs were ventilated using a positive-pressure ventilator driven by phrenic neural activity. Systemic arterial CO2 tension (PaCO2) was elevated by increasing the fraction of CO2 delivered to the ventilator. EEVL was altered from approximated functional residual capacity ("FRC") to 1.5 and 0.5 "FRC" by changing positive end-expiratory pressure. Although the tidal volume (VT)-PaCO2 and inspiratory time (TI)-PaCO2 relationships were not affected, decreasing EEVL from 1.5 "FRC" to "FRC" and then to 0.5 "FRC" caused a significant (p < 0.01) upward shift in the CO2-response curves for minute ventilation (V I) and frequency (f ), and a significant (p < 0.01) downward shift in the CO2- response curve for expiratory time (TE). We conclude that these shifts were explained by a decrease in the inhibitory activity of slowly adapting pulmonary stretch receptors (PSRs) as EEVL was lowered. In addition, increases in EEVL from 0.5 "FRC" to 1.5 "FRC" caused a significant (p < 0.05) increase in the apneic threshold, which we attribute to an inhibitory effect on central drive caused by increased PSR activity.

The effects of haloperidol on visual search, eye movements and psychomotor performance.

The effects of single doses of haloperidol (2, 4 and 6 mg) were compared with lorazepam 2.5 mg and placebo in 15 healthy subjects. Visual search strategy was measured, along with a range of psychomotor and eye movement tests. Patients with Parkinson's disease have been shown to exhibit a shift from parallel to serial processing in visual search, but we demonstrated that this does not occur following administration of either haloperidol or lorazepam. Haloperidol was detected by visual analogue rating scales and peak saccadic velocity, the latter being the more sensitive measure. Haloperidol had no statistically significant effect on smooth pursuit position error, velocity error or saccadic intrusions. Digit symbol substitution performance was clearly diminished by haloperidol, but there was no effect on the continuous attention test. Lorazepam decreased performance in all tests apart from saccadic latency.

A comparison of the sedative and amnestic effects of chlorpromazine and lorazepam.

The effects of single doses of chlorpromazine (100 mg) and lorazepam (0.5, 1 and 2 mg) were compared with placebo in a battery of tests of information processing, working and semantic memory. Peak saccadic velocity was used to provide a precise and reliable measure of sedation and its results were found to be consistent with those using visual analogue rating scales. Chlorpromazine 100 mg was equally sedative to lorazepam 2 mg. Lorazepam caused dose-dependent deterioration in performance in many of the memory tests, whereas an equally sedative dose of chlorpromazine did not. These data therefore support the view that benzodiazepine-induced amnesia is not secondary to sedation. Peak saccadic velocity has considerable advantages over visual analogue scales as a measure of sedation, since it is objective and has a demonstrated low coefficient of variation. It is suggested that saccadic eye movement measurement will permit considerably more reliable and precise separation of the sedative and amnestic effects of drugs and will allow investigation of amnesia caused by clinically relevant doses of psychotropic drugs.

Neonatal capsaicin treatment increases the severity of ozone-induced lung injury.

To test the hypothesis that lung sensory C fibers protect the small distal airways and alveoli from oxidant injury, we compared the effects of inhalation of ozone (1 ppm) or filtered air for 8 h on lung injury and lung inflammation in four groups of rats: (1) normal rats exposed to filtered air; (2) normal rats exposed to ozone; (3) rats treated as neonates with capsaicin (50 mg/kg, intraperitoneally) and subsequently exposed to filtered air; and (4) rats treated as neonates with capsaicin and subsequently exposed to ozone. All rats were allowed to recover in filtered air for 0, 4, 16, and 40 h before necropsy. Rats exposed to filtered air (Groups 1 and 3) showed normal airway and parenchyma structure. Normal untreated rats exposed to ozone showed a random distribution of mild, interstitial inflammatory changes and epithelial necrosis of bronchi and bronchiolar epithelium. However, rats treated with capsaicin and subsequently exposed to ozone demonstrated severe acute interstitial inflammation and epithelial coagulate necrosis in all airways, especially in small, peripheral airways and parenchyma; all of these changes were statistically significant. These findings support our hypothesis that lung sensory C fibers protect the distal airways from oxidant injury during acute ozone inhalation.

Management of debilitating injuries in a large industrial setting.

It has long been the goal of the occupational health specialist to avoid significant impairment or disability from debilitating injury at the work place. This paper is a description of effective and ineffective management strategies with disabling work injuries. Starting proactively with a preventive safety and health program, many of these injuries can be prevented or lessened significantly. When injury does occur, we must examine what can be done to ensure speedy recovery. The elements of prevention, including personal protective programs, ergonomics and pre-placement exams are reviewed. Injury care from early intervention with careful planning of case management involving all providers is also examined, as is the use of rehabilitation for early return to work including work conditioning and work hardening. Also included is how disability guides and a transitional work program can increase rapid recovery. Ultimately, although each element is essential as part of a good management program, the key to success lies in a good employee/employer relationship.

Influence of background vagal C-fiber activity on eupneic breathing pattern in anesthetized dogs.

In 19 dogs anesthetized with xylazine and alpha-chloralose, we examined the influence of background vagal C-fiber activity on the breathing pattern using a modified perineural capsaicin treatment. In seven dogs, we tested the efficacy of this treatment by recording compound action potentials before and after capsaicin application. In the remaining 12 dogs, we examined the effect of vagal perineural capsaicin on the Hering-Breuer expiratory facilitatory inflation reflex, pulmonary chemoreflex, and breathing pattern (tidal volume and expiratory and inspiratory times). Neither the peak height nor integral of the A wave of the compound action potential was significantly affected. However, the peak height and integral of the C wave of the compound action potential were significantly affected. However, the peak height and integral of the C wave of the compound action potential were significantly reduced. The myelinated fiber-initiated Hering-Breuer reflex remained intact after perineural capsaicin, but the C-fiber-initiated pulmonary chemoreflex was abolished. Perineural capsaicin increased tidal volume (0.399 +/- 0.031 to 0.498 +/- 0.058 liter; P < 0.05), expiratory time (3.62 +/- 0.31 to 4.82 +/- 0.68 s; P < 0.05), inspiratory time (1.49 +/- 0.12 to 1.72 +/- 0.17 s; P < 0.10) and total time per breath (5.11 +/- 1.08 to 6.54 +/- 0.82 s; P < 0.05). We conclude that background vagal C-fiber activity exerts an inhibitory effect on tidal volume and an excitatory effect on breathing frequency.

Pulmonary mechanics of dogs during transtracheal jet ventilation.

STUDY OBJECTIVE: To quantify the delivered tidal volume and other selected measurements of pulmonary mechanics in an animal model during transtracheal jet ventilation (TTJV), with comparison to positive-pressure mechanical ventilation (PPMV) and spontaneous breathing. DESIGN: Prospective, nonblinded laboratory animal study. INTERVENTIONS: Seven mongrel dogs weighing 24.5 +/- 3.7 kg were anesthetized, paralyzed, and placed within a specially designed volume plethysmograph with the head and neck externalized. Ventilation was performed using TTJV under variable inspiratory time:expiratory time ratios (TI:TE) (1:1, 1:2, 1:3, 1:4, 1.5:2.5, 2:1, 2:2, 3:1, and 4:1) and variable driving air pressures (40, 45, and 50 psi). The dogs then were ventilated with PPMV. Tidal volume, tracheal pressure, transpulmonary pressure, air flow, arterial pressure, central venous pressure, and arterial blood gases were measured during spontaneous ventilation, TTJV, and PPMV. Quasistatic compliance of the lungs was measured after all methods of ventilation. Statistical significance was accepted at P < .05. RESULTS: There was no significant difference between delivered tidal volume during TTJV (446 +/- 69 mL at a TI:TE of 1:3 and 45 psi) and spontaneous breathing (506 +/- 72 mL). TTJV delivered a tidal volume significantly higher than the standard 15 mL/kg volume used for mechanical ventilation in dogs. Tracheal pressure and transpulmonary pressure were not significantly different between TTJV and PPMV. Variations in TI:TE had no significant effect on most of the measured variables, specifically tidal volume or transpulmonary pressure. Minute ventilation increased significantly and PCO2 decreased significantly as frequency increased during TI:TE settings of 1:1, 1:2, and 2:1. Increases in the driving air pressure during TTJV significantly increased the tidal volume as it was raised from 40 psi to 50 psi. There was no change in quasistatic lung compliance during any method of ventilation. CONCLUSION: TTJV delivers an effective tidal volume comparable to both spontaneous breathing and PPMV in a dog model. In the absence of upper-airway obstruction, there was no significant difference in the pulmonary pressures, resistance, and compliance during TTJV, as compared to mechanical ventilation. Variation in TI:TE during TTJV had no major effect on pulmonary mechanics, except to increase minute ventilation and decrease PCO2 as the frequency was increased significantly. Increasing the driving air pressure to the TTJV apparatus significantly augmented delivered tidal volume due to increased air flow.

Effects of graded upper-airway obstruction on pulmonary mechanics during transtracheal jet ventilation in dogs.

STUDY OBJECTIVE: To quantify the effects of graded upper-airway obstruction on the delivered tidal volume and selected parameters of pulmonary mechanics during transtracheal jet ventilation (TTJV) in a dog model. DESIGN: Laboratory study in which seven dogs were anesthetized, paralyzed, and placed within a volume plethysmograph with the head and neck externalized. INTERVENTIONS: Ventilation was performed using TTJV at 45 psi and a frequency of 15 beats per minute. The upper trachea was occluded progressively using a Foley catheter balloon to induce tracheal pressure levels of approximately 150%, 200%, 250%, and 300% of the tracheal pressure obtained during TTJV-c. Tidal volume, tracheal pressure, transpulmonary pressure, airflow, arterial blood pressure, central venous pressure, and arterial blood gases were measured during all conditions of ventilation. Quasistatic compliance curves of the lungs were measured at the conclusion of spontaneous breathing, TTJV-c, and TTJV (at all levels of obstruction). Minute ventilation and pulmonary flow resistance were calculated for each condition of ventilation. RESULTS: Application of graded upper-airway obstruction during TTJV yielded mean tracheal pressures of 130% (level 1), 190% (level 2), 220% (level 3), and 230% (level 4) of that obtained during TTJV-c (10.9 +/- 2.0 cm H2O). Tidal volume significantly increased with each level of obstruction except between levels 3 and 4 (spontaneous breathing, 506 +/- 72 mL; TTJV-c, 446 +/- 69 mL; level 1, 663 +/- 139 mL; level 2, 780 +/- 140 mL; level 3, 931 +/- 181 mL; and level 4, 944 +/- 135 mL). During TTJV at obstruction level 1, transpulmonary pressure was not significantly higher than either spontaneous breathing or TTJV-c, but did significantly increase during higher levels of obstruction. The mean arterial PCO2 significantly decreased at all levels of obstruction due to significantly increased minute ventilation, with a concomitant increase in arterial pH. There was no significant difference seen in the quasistatic compliance of the lungs among spontaneous breathing, TTJV-c, or TTJV at any level of upper airway obstruction. CONCLUSION: Partial upper-airway obstruction increases the delivered tidal volume, minute ventilation, and transpulmonary pressure of the lungs during TTJV, with consequent decreases in the arterial PCO2 as the amount of obstruction increases. No significant changes were seen in the quasistatic compliance of the lungs, pulmonary flow resistance, or alveolar:arterial gradient, lending support to the position that TTJV is a safe technique under conditions of partial upper-airway obstruction. However, due to significant increases in tidal volume and functional residual capacity and decreases in mean arterial blood pressure, concerns still exist during near-total or total upper-airway obstruction.

Contribution of vagal afferents to respiratory reflexes evoked by acute inhalation of ozone in dogs.

Acute inhalation of ozone induces vagally mediated rapid shallow breathing and bronchoconstriction. In spontaneously breathing anesthetized dogs, we attempted to determine whether afferent vagal C-fibers in the lower airways contributed to these responses. Dogs inhaled 3 ppm ozone for 40-70 min into the lower trachea while cervical vagal temperature was maintained successively at 37, 7, and 0 degrees C. At 37 degrees C, addition of ozone to the inspired air decreased tidal volume and dynamic lung compliance and increased breathing frequency, total lung resistance, and tracheal smooth muscle tension. Ozone still evoked significant effects when conduction in myelinated vagal axons was blocked selectively by cooling the nerves to 7 degrees C. Ozone-induced effects were largely abolished when nonmyelinated vagal axons were blocked by cooling to 0 degree C, breathing during ozone inhalation at 0 degree C being generally similar to that during air breathing at 0 degree C, except that minute volume and inspiratory flow were higher. We conclude that afferent vagal C-fibers in the lower airways make a major contribution to the acute respiratory effects of ozone and that nonvagal afferents contribute to the effects that survive vagal blockade.

Acute inhalation of ozone stimulates bronchial C-fibers and rapidly adapting receptors in dogs.

To identify the afferents responsible for initiating the vagally mediated respiratory changes evoked by acute exposure to ozone, we recorded vagal impulses in anesthetized, open-chest, artificially ventilated dogs and examined the pulmonary afferent response to ozone (2-3 ppm in air) delivered to the lower trachea for 20-60 min. Bronchial C-fibers (BrCs) were the lung afferents most susceptible to ozone, the activity of 10 of 11 BrCs increasing from 0.2 +/- 0.2 to 4.6 +/- 1.3 impulses/s within 1-7 min of ozone exposure. Ten of 15 rapidly adapting receptors (RARs) were stimulated by ozone, their activity increasing from 1.5 +/- 0.4 to 4.7 +/- 0.7 impulses/s. Stimulation of RARs (but not of BrCs) appeared secondary to the ozone-induced reduction of lung compliance because it was abolished by hyperinflation of the lungs. Ozone had little effect on pulmonary C-fibers or slowly adapting pulmonary stretch receptors. Our results suggest that both BrCs and RARs contribute to the tachypnea and bronchoconstriction evoked by acute exposure to ozone when vagal conduction is intact and that BrCs alone are responsible for the vagally mediated tachypnea that survives vagal cooling to 7 degrees C.