Decrease In Tidal Volume Research Articles

Effect of dorsal displacement of the soft palate on ventilation and airflow during high-intensity exercise.

Dorsal displacement of the soft palate (DDSP) is one of the most common obstructive conditions of the upper respiratory tract in the racehorse. The present study was conducted to determine the effects of intermittent dorsal displacement of the soft palate (DDSP) on ventilation and respiratory airflow during high intensity exercise. Videoendoscopic recordings were made of the nasopharynx and larynx simultaneously with measurements of airflow and respiratory gas exchange, during high-speed treadmill exercise in 9 horses with confirmed intermittent DDSP admitted for clinical investigation of poor racing performance. In all horses, DDSP resulted in a reduction in minute ventilation (VE) (P<0.001), associated with a decrease in tidal volume (VT) (P<0.01) with no change in breathing frequency (f) and a reduction in oxygen consumption (VO2) (P<0.01). Further, DDSP resulted in reduction of expiratory flow parameters, including peak expiratory flow (PEF), EF50, EF25 and EF125 (P<0.01), with no alteration of inspiratory flow. These results confirm that naturally-occurring intermittent DDSP creates a flow-limiting expiratory obstruction. The associated impairment of athletic performance is probably caused, at least in part, by the accompanying decrease of oxygen uptake.

Contralateral Tension Pneumothorax During One-Lung Ventilation for Lobectomy: Diagnosis Aided by Fiberoptic Bronchoscopy

Contralateral Tension Pneumothorax During One-Lung Ventilation for Lobectomy: Diagnosis Aided by Fiberoptic Bronchoscopy

Comparative evaluation of ultrasonography and lung function testing with the clinical signs and pathology of calves inoculated experimentally with Pasteurella muftocida

Seventeen calves were inoculated intratracheally with Pasteurelia multocida D on three consecutive days with 10 ml of an inoculum containing 109 colony forming units/ml per day per calf. Before the...

Capnography and Severe COPD

To The Editor: The influences of chronic obstructive pulmonary disease (COPD) on end-tidal CO2 concentration (ETco2) monitoring are well known and consist primarily of the appearance of a significant gradient Paco2/ETco2 secondary to the increase of the alveolar dead space, and the appearance of an ascending capnogram, of which the slope is proportional to the degree of expiratory airway obstruction (1). The extreme stressing of these phenomena can lead to surprising clinical presentations, one of which is described below. A 51-yr-old female patient was scheduled for bilateral thoracoscopic lung reduction for severe postnicotinic bronchoemphysema. Preoperatively, forced vital capacity and FEV1 were 58% and 16%, of normal values, respectively, and Pao2 and Paco2 in air were 59 and 46 mm Hg, respectively. Ventilation and perfusion ratios were respectively 33% and 34% for the left lung and 67% and 66% for the right lung. Anesthesia consisted of a combined thoracic epidural analgesia and general anesthesia that included propofol, sufentanil, and cisatracurium. The trachea was easily intubated with a 37-ch left double-lumen endotracheal tube, of which the right positioning was checked by fibroscopy. Ventilation was controlled with a Fio2 of 0.5, with a maximal peak pressure limit set to 30 cm H2O, at a frequency of 12 breaths/min. Ten minutes after initiation of the mechanical ventilation, ETco2 was 31 mm Hg for a Paco2 value of 47 mm Hg. The operation was performed in dorsal decubitus. The left pulmonary reduction was uneventfully achieved in 68 min during one-lung ventilation. The right thoracoscopy was then started after the exclusion of the right lung. The total absence of a reading on the capnogram was noticed concomitant to the development of increased insufflation pressure and a decrease of tidal volume (120 mL). The permeability of both the endotracheal tube and the left bronchial tree were then checked again by fibroscopy. Surprisingly, the Sao2 remained normal. The reventilation of the right lung systematically allowed the reappearance of breathed out CO2 as well as a slight increase of the tidal volume, whereas the left one-lung ventilation was always associated with a “flatline” capnogram. The examination of the patient did not reveal the cause of this problem. The thoracic drain of the left side had a moderate air leak, but this could not explain the clinical picture by itself. It was then noticed that a several-seconds period of apnea resulted in a very slow appearance of CO2 coming from the left lung. Obviously, the degree of expiratory obstruction of the left lung airway were such that the extent of the ascending inclination of the ETco2 did not allow the appearance of CO2 while breathing out before occurrence of the next ventilatory cycle (Fig. 1). The reason for this was probably a result of the severity of the broncoemphysematic pathology on the left side, increased by the fact that this lung had been previously nonventilated during 68 min, which most certainly caused a slight interstitial edema, worsening the degree of stenosis of the small airways. Last, the presence of the bronchopleural air leak could explain the persistence of moderate alveolar ventilation although no ETco2 has been measured. Obviously, our patient was hypoventilated (maximum Paco2 value of 70.7 mm Hg) because of the important increase of the insufflation pressures of the left side and the subsequent decreasing of its tidal volume, but its oxygenation remained satisfactory. Finally, the right pulmonary reduction was completed in 50 min. The return to two-lung ventilation allowed the reappearance of ETco2, and the trachea could finally be extubated just after the procedure.Figure 1: ETco2 (upper curve) and airway pressure (lower curve) trends showing absence of capnogram during mechanical ventilation (small arrows) and progressive appearance of ETco2 during a period of apnea (large arrow) resulting from severe expiratory airway obstruction.In conclusion, the absence of capnographic reading in patients showing severe COPD is not an absolute indicator of no ventilation. Serge M. Broka, MD Sihem Boujlel, MD

Assessment of the use of the laryngeal tube for cardiopulmonary resuscitation in a manikin

During 60 3-min CPR sequences, the face mask, laryngeal tube and tracheal tube were compared using an Ambu Megacode Trainer. Ten 3-min sequences each were performed for both a combination of the face mask and laryngeal tube with a bag-valve device (compression–ventilation ratio 5:1). With continuous chest compressions, ten 3-min CPR sequences each were performed for a combination of the laryngeal tube and tracheal tube with a bag-valve device and ten 3-min CPR sequences each for a combination of the laryngeal tube and tracheal tube with an automatic transport ventilator. Signs of gastric inflation occurred only with the face mask. Ventilation with the laryngeal tube was significantly better than with the face mask and comparable to the tracheal tube during ventilation with the bag-valve device and with the automatic transport ventilator. Chest compressions caused a significant decrease in tidal volumes during ventilation with the automatic transport ventilator. The findings of this study support the idea of the laryngeal tube as a new adjunct for emergency airway management, but will have to be verified during clinical practice.

Effect of delayed sternal closure after cardiac surgery on respiratory function in ventilated infants.

Studies examining the effect of sternal closure on respiratory function have not been published, and currently there is little evidence to guide ventilation management immediately after closure. The aim of this study was to establish the impact of delayed sternal closure on expired tidal volume, respiratory system compliance, and CO2 elimination immediately after the procedure in infants who had undergone open heart surgery. Prospective study of respiratory function before and after delayed sternal closure. Cardiac intensive care unit, Great Ormond Street Hospital, London. Seventeen infants (median age, 2 wks) with open median sternotomy incisions after cardiac surgery. Data were collected between August 1998 and March 2000. Respiratory function was measured continuously for 30 mins before and after delayed sternal closure in paralyzed ventilated infants. Four babies were excluded from the study because they required either immediate increase in ventilation after delayed sternal closure (n = 3) or removal of pericardial blood collection (n = 1). In the remaining 13 infants, expired tidal volume and CO2 elimination decreased significantly (p < .005) by a mean of 17% and 29%, respectively, after sternal closure. In five of the remaining 13 patients, the magnitude of tracheal tube leak increased by > or = 10% after delayed sternal closure, thereby invalidating recorded changes in respiratory system compliance. Of the eight infants in whom there was a minimal change in leak, respiratory system compliance decreased significantly (p < .05) by a mean of 19%. This study supports the hypothesis that respiratory function may be compromised after delayed sternal closure and that ventilatory support should be increased to counteract the anticipated decrease in tidal volume. Extra vigilance should be applied in monitoring blood gases after delayed sternal closure to assess clinical responses to sternal closure or changes in ventilatory support. Accurate assessment of change in respiratory system compliance after any therapeutic intervention may be precluded by changes in tracheal tube leak during the procedure.

Airway ammonia negates the normal ventilatory response to airway CO 2 in garter snakes

Earlier studies from this lab showed that unidirectionally ventilated snakes, maintained on high airway [CO 2], breathe slowly with a large tidal volume. If airway [CO 2] is abruptly reduced during inspiration, inspiratory duration ( ti) and tidal volume increase. On the other hand, in an animal normally receiving fresh air (no CO 2 in the inspired air) on each inspiration, if fresh air is withheld for one breath, ti and tidal volume decrease. To test the effect of producing an alkaline environment in the presence of CO 2 during these two maneuvers, six unidirectionally ventilated snakes weighing 32±16 g were maintained on 4% CO 2 in air flowing at 300 ml/min even during inspiration. NH 3 (4%) was introduced into the lung during one inspiration. During that breath, ti increased significantly, as if CO 2 had been removed from the lung. In another study, six different snakes weighing 21±6 g received fresh air at each inspiration. At the end of inspiration [CO 2] was again raised to 4%. However, for one breath, [CO 2] was maintained high during inspiration and airway NH 3 (3–4%) was simultaneously introduced into the airstream. During this breath, ti was expected to decrease, owing to the elevated [CO 2]; however, there was no significant difference in the ti of the test breath compared with the previous breath, indicating that ammonia interfered with the expected CO 2 response. This study suggests that pH (probably intracellular) rather than P CO 2 produces this ventilatory reflex.

Is It Safe for Patients With Chronic Hypercapnic Respiratory Failure Undergoing Home Noninvasive Ventilation To Discontinue Ventilation Briefly?

A brief discontinuation (< 1 week) of long-term ventilation may be necessary in patients who are not totally ventilator-dependent in cases of technical problems, intolerable nasal irritation, upper airway congestion, or travel. We examined the incidence, timing, and causes of possible clinical deterioration after a brief withdrawal of ventilation in patients with chronic respiratory failure (CRF) who were well-established on long-term noninvasive mechanical ventilation (NIMV). Prospective clinical study. Eleven inpatients in clinically stable condition (COPD, 6 patients; and restrictive thoracic disease [RTD], 5 patients) who had severe CRF (PaCO(2), > 50 mm Hg) and had been receiving NIMV for (mean +/- SD) 19.3 +/- 5.3 months were enrolled. Arterial blood gas (ABG) levels, maximal inspiratory pressure (PImax), breathing pattern, dyspnea rating, and life symptoms (measured by a questionnaire) were recorded daily after NIMV withdrawal for 6 days or until the patients showed clinical and/or ABG level deterioration. Pulmonary function tests were performed and neuromuscular drive was measured at the beginning and the end of the study. Five of the 11 patients (45.4%) [COPD, 3 patients; and RTD, 2 patients] were reconnected to a ventilator before the scheduled time because of ABG level deterioration. Despite these changes, none of the patients reported severe worsening of symptoms or other medical complications. The patients whose ABG levels worsened had statistically significant decreases in tidal volume and PImax, suggesting that the development of alveolar hypoventilation was related to respiratory muscle weakness. A brief discontinuation of NIMV in patients who were affected by chronic hypercapnic respiratory failure and were well-established on NIMV is associated with a relatively high incidence of ABG level worsening due to the development of alveolar hypoventilation. If NIMV must be briefly interrupted for clinical reasons, the patient should be monitored closely for abrupt worsening, and prompt technical intervention should be provided if a ventilator fails.

Ventilatory responses to ozone are reduced in immature rats.

During ozone (O(3)) exposure, adult rats decrease their minute ventilation (VE). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O(3) (2 ppm) in nose-only-exposure plethysmographs. Baseline VE normalized for body weight decreased with age from 2.1 +/- 0.1 ml. min(-1). g(-1) in 2-wk-old rats to 0. 72 +/- 0.03 ml. min(-1). g(-1) in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O(3) caused 40-50% decreases in VE that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O(3)-induced changes in VE were significantly less, and in 2- and 4-wk-old rats, no significant changes in VE were observed during O(3) exposure. The increased baseline VE and the smaller decrements in VE induced by O(3) in the immature rats imply that their delivered dose of O(3) is much higher than in adult rats. To determine whether these differences in O(3) dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O(3) was significantly greater in 2- than in 8-wk-old rats (267 +/- 47 vs. 165 +/- 22%, respectively, P < 0.05). O(3) exposure also caused a significant increase in PGE(2) in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O(3) is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.

Vagal and mediator mechanisms underlying the tachypnea caused by pulmonary air embolism in dogs.

We investigated the vagal and mediator mechanisms underlying the tachypnea caused by pulmonary air embolism (PAE) in anesthetized and spontaneously breathing dogs. PAE was induced by infusion of air into the right atrium (0.2 ml. kg(-1). min(-1) for 10 min). The first PAE induction caused an increase in respiratory frequency accompanied by a decrease in tidal volume in each of the 30 animals studied. Subsequently, animals were evenly divided into five groups, and a second PAE induction was repeated after various experimental interventions. The tachypneic response to PAE was not significantly altered by pretreatment with a saline vehicle but was largely attenuated by either perivagal capsaicin treatment (a technique that selectively blocks the conduction of unmyelinated C fibers), pretreatment with ibuprofen (a cyclooxygenase inhibitor), or pretreatment with dimethylthiourea (a hydroxyl radical scavenger). Ultimately, the tachypneic response was nearly abolished by a bilateral cervical vagotomy. These results suggest that 1) lung vagal unmyelinated C-fiber afferents play a predominant role in evoking the reflex tachypneic response to PAE and 2) both cyclooxygenase products and hydroxyl radical are important in eliciting this vagally mediated response.

The effect of intratracheal pulmonary ventilation on the decrease of dead space in rabbits with acute respiratory failure.

A technique that improves the efficiency of alveolar ventilation should decrease the pressure required and reduce the potential for lung injury during mechanical ventilation. High partial pressure of carbon dioxide (PaCO2) can be tolerated if associated with a lower airway pressure as in permissive hypercapnia (PH). Intratracheal pulmonary ventilation (ITPV) was developed to allow a decrease in physiological dead space during mechanical ventilation. We compared the effect of hybrid ventilation (HV) as a modification of ITPV with PH on the decrease of tidal volume and airway pressures in rabbits with acute respiratory failure. Tracheostomy was performed in seven rabbits ventilated under volume-controlled mode in the supine position. Arterial blood gas analysis, airway pressures, and dead space ventilation were measured at respiratory rates of 20/min as control values. Oleic acid (OA) of 0.06 mL/kg was injected to induce acute respiratory failure. Tidal volume (V(T)) was elevated to maintain PaCO2 in the normal range. These same parameters were measured as OA values. Then V(T) was reduced to the control level to allow PH. Hybrid ventilation was initiated by inserting a reverse thrust catheter (RTC) into the endotracheal tube. Hybrid ventilation consists of a pressure-controlled mode of mechanical ventilation and ITPV while flushing fresh gas continuously via the RTC. Respiratory parameters were compared under control, OA, PH and HV conditions. Oleic acid injection decreased partial pressure of oxygen (PaCO2) from 401+/-35 mmHg to 129+/-39 mmHg, increased V(T) from 42+/-5 mL to 52+/-10 mL, and increased dead space (V(D))/V(T) ratio from 0.65+/-0.07 to 0.71+/-0.07. During PH, the increase in PaCO2 was accompanied by an increase in V(D)/V(T) ratio from 0.71+/-0.07 to 0.79+/-0.03 and by a decrease of peak inspiratory pressure (PIP) from 19.4+/-4.0 cmH2O to 16.8+/-3.1 cmH2O. PaCO2 was lowered from 50+/-5 mmHg in PH to 39+/-5 mmHg in HV with a lower V(T). V(D)/V(T) ratio in HV which was as low as that in control. Hybrid ventilation is an effective and easy-to-use ventilatory modality to reduce PaCO2 and airway pressures by the reduction in V(D)/V(T) ratio in acute respiratory failure model.

COMBINED RESPIRATORY EFFECTS OF COLD AIR WITH SO2 OR NO2 IN SINGLE 1-HOUR EXPOSURES OF HYPERVENTILATING GUINEA PIGS

The present study is a continuation of our previous experiments on repeated 10-min exposures of anesthetized, mechanically ventilated guinea pigs to clean cold dry air (Hälinen et al., 2000a), and to cold air plus gaseous air pollutants (Hälinen et al., 2000b). This time we made continuous 60-min exposures to clean cold dry air, cold air + SO2 at 1 ppm, cold air + NO2 at 1 ppm, and warm humid air + NO2 at 1 ppm, and focused on responses at 10-60 min. Clean cold dry air and cold air + pollutants (n = 8-9 in each group) produced similar cooling in the guinea pig lower respiratory tract. The decreases in intratracheal temperature (Ttr) reached a plateau at 20 min with mean maximal decreases of 9.7-11.3°C from the pre-exposure control values of 36.0-37.3°C. In contrast, there were progressive decreases in esophageal temperature (Toe) during the exposures, indicating constant conductive and evaporative heat losses from the tracheobronchial tissues. The mean maximal decreases in Toe were 1.2-1.4°C from the preexposure control values of 37.8-38.0°C. Clean cold dry air induced 4.5-10.8% mean decreases in peak expiratory flow (PEF) at 10-60 min of exposure, which were statistically nonsignificant due to a relatively large variation between animals. Cold air + SO2 at 1 ppm induced a mean decrease of 11.4% in PEF at 10 min (p < .05), which was spontaneously abolished during the next 10 min of exposure. Cold air + NO2 at 1 ppm caused no decrease, but in fact small, nonsignificant increases in PEF at 30-60 min of exposure. Cold air + NO2 at 1 ppm, and to some extent also cold air + SO2 at 1 ppm, attenuated significantly the mechanical ventilation induced gradual decrease in tidal volume (VT), when compared to clean cold dry air exposure. Cold air + NO2 at 1 ppm, but not warm humid air + NO2 at 1 ppm, increased significantly the proportion of macrophages in the differential count of bronchoalveolar lavage fluid (BALF) white cells when compared to both clean warm humid air and cold dry air. None of the exposure conditions caused morphological or inflammatory changes in the respiratory tissues. In conclusion, continuous 60-min exposures to clean cold dry air, cold air + SO2, and cold air + NO2 produced weaker functional effects on the lower respiratory tract of guinea pigs than our previous consecutive 10-min exposures to these air conditions. After the first 10 min, there was a strong attenuation of the bronchoconstrictor responses, especially to cold air + NO2 at 1 ppm. The small airway effects of prolonged mechanical ventilation were significantly modified by NO2 at 1 ppm in both cold dry and warm humid breathing air. Finally, cold air + NO2 at 1 ppm increased the proportion of macrophages in BALF white cells.

Anesthesia of the superior laryngeal nerves and tartaric acid-Induced cough

Objective: The internal branch of the superior laryngeal nerve (ibSLN) conveys impulses for the laryngeal cough reflex, which protects the laryngeal aditus and prevents the development of aspiration pneumonia. The purpose of this study was to determine the effect of bilateral anesthesia of the ibSLN on the cough reflex after inhalation of a nebulized chemoirritant solution of tartaric acid. Design: Prospective, clinical investigation. Setting: Outpatient. Participants: Nine healthy volunteers. Interventions: Bilateral injections of 2% lidocaine solution without epinephrine into the paraglottic space containing the ibSLN. Main Outcome Measures: The tidal volume after inhalation of a nebulized 20% tartaric acid solution and forced vital capacity (FVC) were measured before and after injection. Data were analyzed using the Wilcoxon signed ranks, Mann-Whitney, and sign tests. Results: Complete anesthesia of the ibSLN abolished the laryngeal cough reflex. Postinjection tidal volumes were significantly lower than preinjection volumes ( p < .01). The decrease in tidal volumes for six subjects with complete bilateral anesthesia was significantly larger than the decrease in tidal volumes for three subjects with partial anesthesia ( p < .05). FVC in both the six subjects with complete bilateral anesthesia and the three subjects with partial anesthesia did not significantly change from preinjection to postinjection. None of the subjects in this study had complications or adverse respiratory sequelae. Conclusion: Tartaric acid-induced cough may be useful in assessing the integrity of the laryngeal cough reflex after anesthesia or in patients with neurologic injury who are at risk of developing aspiration pneumonia. It may also be useful in making the decision whether to resume oral feeding.

Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea.

The response to inspiratory resistance loading (IRL) of the upper airway during sleep in children is not known. We, therefore, evaluated the arousal responses to IRL during sleep in children with the obstructive sleep apnea syndrome (OSAS) compared with controls. Children with OSAS aroused at a higher load than did controls (23 +/- 8 vs. 15 +/- 7 cmH(2)O. l(-1). s; P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs. non-REM sleep (P < 0.001), whereas normal subjects had lower arousal thresholds during REM (P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 +/- 17% of baseline at an IRL of 15 cmH(2)O. l(-1). min; P < 0.001) and after 3 min of IRL (67 +/- 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Despite compensatory changes in respiratory timing, normal children have a decrease in minute ventilation in response to IRL during sleep. However, arousal occurs before gas-exchange abnormalities.

Observations on some cardiopulmonary effects of midazolam, xylazine and a midazolam / ketamine combination in the goat

Xylazine, midazolam and a midazolam/ketamine combination were administered to 6 goats in a randomised 3-way block design. All goats received all treatments with at least a 7-day interval between treatments. Statistically significant (P < 0.05) changes were observed in some of the measured cardiopulmonary variables for xylazine and midazolam/ ketamine. Xylazine administration resulted in statistically significant decreases in minute volume, arterial partial pressure of oxygen, heart rate and mean arterial blood pressure. The increase in arterial partial pressure of carbon dioxide was not statistically significant. For the midazolam/ketamine combination, the decrease in tidal volume was statistically significant, but not the decrease in minute volume and increase in arterial partial pressure of carbon dioxide. The decrease in the arterial partial pressure of oxygen was also statistically significant. The mean arterial blood pressure for the combination was statistically significantly higher compared to xylazine. The changes in cardiopulmonary variables after midazolam administration were not statistically significant, such as tidal and minute volume, arterial partial pressure of oxygen and carbon dioxide. However, clinically significant effects such as hypoventilation and hypoxia were observed after its administration. The change in mean arterial blood pressure was minimal.

Control of breathing, respiratory patterns and dyspnoea in patients with congestive heart failure

The aim of this paper was the evaluation of the control of breathing and respiratory patterns in patients with congestive heart failure (CHF) and its relation with the genesis of dyspnoea. Forty seven patients were studied with CHF, with a mean age of 60.9±12.5 years and compared them with 35 age-matched controls, free of cardiopulmonary diseases. The evaluation included: (a) measurements of lung function using the helium dilution method; (b) determination of occlusion pressure (P0.1) at rest; (c) noninvasive breathing pattern at rest assessed by means of respiratory inductive plethysmography (RIP); (d) CO 2 re-breathing test with the simultaneous recording of ventilation, P0.1 and dyspnoea perception using a visual analogue scale. A mild restrictive ventilatory defect was found in CHF patients, together with an abnormal breathing pattern at rest defined by a significant increase in respiratory frequency and a decrease in tidal volume, when compared with the control group. However, the mean pulmonary ventilation at rest did not differ between the two groups whereas the baseline P0.1 was higher in CHF, (median 1.6; range 2.00 cmH 2O), than in controls (median 1.20; range 1.00 cmH 2O), ( P<0.001). The slope of the ventilatory response to hypercapnia was significantly lower in CHF patients, (median 0.93; range 1.95 l/min per mmHgCO 2), than in controls (median 1.30; range 1.29), ( P<0.006). However, the slope of P0.1, was similar in both groups, whereas the slope of dyspnoea perception was higher in CHF but not statistically significant. In conclusion, despite having a higher central drive at rest the CHF patients responded to hypercapnia with a slope of P0.1 similar to that of controls, however, the ventilatory response was lower and not generally accompanied by a higher sensation of dyspnoea. These findings do not favour an inappropriate increase in ventilation as a major cause of dyspnoea in CHF patients.

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.

Role of the cholinergic pathway in mediating platelet-activating factor-induced pulmonary dysfunctions in unsedated calves.

The purpose of this study was to investigate the possible role of the cholinergic pathway in mediating platelet-activating factor (PAF)-induced pulmonary dysfunctions in unsedated calves. In a placebo group, PAF infusion challenge induced significant dysfunctions in the pattern of breathing [a significant increase in respiratory rate (RR) and a significant decrease in tidal volume (VT)], the mechanics of breathing [a significant increase in total lung resistance (RL) and a significant decrease in dynamic lung compliance (CLdyn)] and gas exchange, whereas in atropine pre-treated calves, PAF infusion challenge induced a significant increase in RR, VT and HR and a significant decrease in CLdyn. The RL increase was prevented by atropine pre-treatment. On the basis of our findings, we suggest that, in cattle, the PAF-induced pattern of breathing dysfunctions and the diffuse bronchoconstriction and microvascular leakage of small airways are not mediated through the cholinergic pathway. By contrast, our data suggest that PAF-induced bronchoconstriction of upper airways is at least partly mediated through muscarinic receptors.

Comparative effects of a glucocorticosteroid, theophylline and the peptido-leukotriene-antagonist CGP 45715A on antigen-induced early and late phase airway response and inflammatory cell influx in sensitised guinea pigs

A novel model of allergic early and late-phase reaction in the airways of conscious guinea pigs was developed and the effect of established and novel antiasthmatic drugs on peak of immediate response, late phase response and associated inflammatory cell influx investigated. Guinea pigs were sensitised twice in adjuvant (50 mg/kg silica+0.1 ml/kg Bordetella pertussis). Under cover of 10 mg/kg i.p. mepyramine guinea pigs exhibited still a pronounced immediate reaction. During a screening phase about 75% of guinea pigs demonstrated a late phase reaction of decrease of tidal volume between 4–10 h after ovalbumin inhalation. In a cross over study theophylline at 50 mg/kg p.o. (−1 h before ovalbumin) tended to attenuate not only the peak of the immediate reaction by about 69% ( P>0.05, n=12), but inhibited the airway late phase response significantly ( P<0.05, 5–10 h, n=12). Methylprednisolone (40 mg/kg p.o. 1 h before ovalbumin) did not inhibit the immediate response, but the late phase response. In contrast the cysteinyl-leukotriene antagonist CGP 45715A (Iralukast; 30 mg/kg p.o. 2 h before ovalbumin) neither interfered with the peak of the immediate, nor with the late phase response. When bronchoalveolar lavage by orotracheal route was performed 24 h after ovalbumin inhalation, total cell count, eosinophils, neutrophils, macrophages and lymphocytes were significantly increased in ovalbumin-controls compared to sham ( n=5; P<0.05). Methylprednisolone reduced significantly the antigen-induced increase of total cell count and eosinophil number. Neither theophylline nor the cysteinyl-leukotriene receptor antagonist attenuated the antigen-associated cell influx. The results do not provide evidence for a major role of cysteinyl-leukotrienes in the late phase response and inflammatory cell influx in this model.

Acute ventilatory restriction in children after weaning off inhaled nitric oxide: relation to rebound pulmonary hypertension.

To assess the interaction between pulmonary hemodynamics and respiratory mechanics during acute pulmonary hypertension. Ventilated and paralysed children treated with inhaled nitric oxide because of post-operative pulmonary hypertension. Weaning of inhaled nitric oxide. Air flow and airway pressure, calculation of dynamic respiratory system compliance and respiratory system resistance for each breath by multiple linear regression. In four patients, increases in pulmonary arterial pressure from 26.1 to 56.7 mm Hg (p<0.001) during weaning off nitric oxide were associated with decreases in tidal volume (from 9.7-->8.2 ml/kg, p<0.01) and reductions in dynamic respiratory system compliance (from 0.52-->0.34 cm H20/ml/kg, p<0.001), while respiratory system resistance was unchanged. Impaired ventilation during acute pulmonary hypertension is predominantly related to a reduction in respiratory system compliance.