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H Lorino

Publications and source records attributed to H Lorino.

At least 37 records · Page 2Linked to original sources

Respiratory resistance by end-inspiratory occlusion and forced oscillations in intubated patients.

Measurement of respiratory impedance by the forced oscillation technique (FOT) in intubated patients requires corrections for the flow-dependent resistance, inertance, and air compression inside the endotracheal tube (ETT). Recently, we published a method to correct respiratory impedance for the mechanical contribution of the ETT. To validate this correction, we compared the respiratory resistance obtained with this method (Rfo) to the intrinsic (Rmin) and total resistances (RT) measured by the airway-occlusion technique (OCT) in 16 intubated sedated paralyzed ventilated patients. The FOT was applied at functional residual capacity in the 4- to 32-Hz frequency range, whereas the OCT was performed at the end of a normal constant-flow inspiration. Rmin corrected with Rfo measured at 16 and 32 Hz [Rfo(16) = 1.10 x Rmin + 0.10 cmH2O.s.l-1, r = 0.96, P < 0.001; Rfo(32) = 0.93 x Rmin + 0.72 cmH2O.s.l-1, r = 0.97, P < 0.001]. RT corrected with Rfo at 4 Hz [Rfo(4) = 1.11 x RT - 1.48 cmH2O.s.l-1; = 0.92; P < 0.001]. We conclude that the FOT improved by correction for the behavior of the ETT is in good agreement with the OCT in intubated patients.

Adult↗

Effects of assisted ventilation on the work of breathing: volume-controlled versus pressure-controlled ventilation.

During assisted ventilation, the same tidal volume can be delivered in different ways, with the possibility for the physician to vary the ventilatory target (pressure or volume) and the peak flow setting. We compared the effects on the respiratory work rate of assisted ventilation, delivered either with a square wave flow pattern (assist control ventilation [ACV]) or with a decelerating flow pattern and a constant pressure (assisted pressure-control ventilation [APCV]). In the first part of the study where seven patients were studied, inspiratory time and tidal volume were similar in the two modes of ventilation. High and moderate levels of tidal volume (VT) were studied (12 ml/kg and 8 ml/kg, respectively). To obtain moderate VT, inspiratory time was kept constant and, therefore, mean inspiratory flow was reduced. At high VT, no difference between ACV and APCV was noted for breathing pattern, respiratory drive indexes, respiratory muscle work, or arterial blood gases. All patients exhibited respiratory alkalosis. At moderate VT, normal pH was achieved. In this situation significantly lower levels were observed during APCV than during ACV for the power of breathing (10 +/- 2 versus 19 +/- 5 J/min, p<0.05), transdiaphragmatic pressure swing (7 +/- 1 versus 11 +/- 2 cm H2O, p<0.05), and pressure-time index (252 +/- 43 versus 484 +/- 114 cm H2O.s, p<0.05), even though breathing pattern and gas exchange were similar. In the second part of the study where six additional patients were studied, tidal volume was kept constant at a moderate level (8 ml/kg), and we studied the effect of shortening inspiratory time and increasing mean inspiratory flow. At moderate VT and high inspiratory flow, no significant differences could be found between ACV and APCV, and although pressure-time index tended to be lower during APCV, absolute levels of effort were of small magnitude (56 +/- 55 versus 76 +/- 55 cm H2O.s). We conclude that at moderate VT and low flow rates only, inspiratory assistance delivered at a constant pressure reduces the respiratory work rate more effectively than assist control ventilation.

Aged↗

Patient-triggered ventilation decreases the work of breathing in neonates.

During conventional intermittent mandatory ventilation (IMV) in neonates, asynchrony between mechanical and spontaneous breaths is frequent. We tested the hypothesis that patient-triggered ventilation (PTV) reduces the work of breathing (WOB) by providing synchronized assistance for each breath. Accordingly, six intubated preterm infants were studied at the median postnatal age of 34 days while they were being weaned from mechanical ventilation (MV). Patients were ventilated using the Draeger Babylog 8000 (software #3) and studied in four successive modes of MV with a constant level of positive end-expiratory pressure. They were randomly assigned to IMV, PTV with peak inspiratory pressure of either 10 cm H2O (PTV10) or 15 cm H2O (PTV15), and spontaneous ventilation with continuous positive airway pressure. PTV was achieved in the assist/control mode. During PTV, infants adapted their pattern of breathing in response to an increase in tidal volume (median 7.5 ml/kg in IMV versus 8.2 in PTV10 and 8.5 in PTV15, p<0.05) by decreasing their respiratory rate, thus maintaining minute ventilation (439 ml/min/kg in IMV versus 422 in PTV10 and 455 in PTV15, NS) and transcutaneous CO2. WOB fell significantly during PTV compared with its level during IMV (0.81 J/L in IMV versus 0.48 and 0.47 during PTV10 and PTV15, respectively, p<0.05). Power of breathing decreased in the same proportions. These results demonstrate that PTV mode allows reduction of the workload imposed on the respiratory muscles.

Adaptation, Physiological↗

Home versus intensive care pressure support devices. Experimental and clinical comparison.

A bench study using an artificial lung model and a clinical study in patients were performed to evaluate six commercially available home pressure support devices. Six devices were tested in the in vitro study, including five designed for home use and one designed for use in intensive care units. Minimal positive end-expiratory pressure (PEEP) varied across home devices, from 0.5 cm H2O to 4.3 cm H2O. Work imposed during exhalation varied up to six-fold across devices. A substantial rebreathing volume has present for the three home devices with a common inspiratory and expiratory line. This rebreathing volume decreased with increasing PEEP level, as expected, but remained substantial at the widely used PEEP level of 5 cm H2O. Use of a non-rebreathing valve increased both the work imposed by the circuit during the exhalation phase and the time required to attain the relaxation equilibrium. Except for two home devices and a bilevel positive airway pressure (BiPAP) device equipped with a non-rebreathing valve, differences in inspiratory trigger sensitivities were small between home and intensive care devices. During pressure support, the total work performed by the machines did not differ by more than 15% between devices, whereas differences of more than 300% were observed in flow acceleration. Only one home device gave a flow acceleration similar to or better than that obtained with the intensive care device. In a randomized, crossover clinical study, we compared a home device to a device specially designed for intensive care use in seven intubated patients during weaning from mechanical ventilation. The main differences between the two devices were trigger sensitivity and initial flow acceleration. For the same level of pressure support, there were no significant differences in arterial PCO2, tidal volume, respiratory rate, or minute ventilation between these two devices. However, the esophageal pressure-time product was 30% higher with the home device (165 +/- 93 versus 119 +/- 80 cm H2O/min, p < 0.05). In conclusion, differences exist between devices in terms of occurrence of rebreathing, speed of attainment of stable pressure support level, and expiratory resistance. These differences characterizing the delivery of pressure support may have clinical impact on the inspiratory effort of patients.

Adult↗

A new correction technique for measuring respiratory impedance through an endotracheal tube.

Measurement of respiratory impedance (Zrs) in intubated patients requires corrections for flow-dependent resistance and air compression inside the endotracheal tube (ET). The purpose of this study was to test a new correction technique for these effects. We therefore studied 110 patients in two conditions: breathing normally (C1), or breathing through an ET placed at the mouth (C2). In C1, we measured pressure and flow signals at the mouth, and in C2, at the ET inlet, during application of a pseudorandom forced excitation (4-32 Hz). In C1, respiratory impedance was calculated directly as Z1. In C2, pressure data were first corrected for the flow-dependent resistance of the ET, and respiratory impedance was then corrected both for gas compression inside the set-up and ET inertance (impedance Z2). Strong linear relationships were found between the reference and corrected estimates of the resistance at 6 Hz, the frequency dependence of resistance and the resonant frequency. The mean normalized distance between Z1 and Z2 observed in the patients over the 4-32 Hz frequency range was about 14% for resistance and 12% for reactance (-9% and -4%, respectively, when considering the algebraic value of the distance). This slight underestimation of both components of impedance might be due to an overcorrection of pressure for the flow-dependent resistance of the ET. We conclude that, in intubated patients, newly tested corrections for the mechanical contribution of the endotracheal tube may yield a fair estimate of respiratory impedance when pressure is measured at the inlet of the endotracheal tube.

Airway Resistance↗

Comparison of the effects of pressure support ventilation delivered by three different ventilators during weaning from mechanical ventilation.

OBJECTIVE: To compare the effects of pressure support ventilation (PSV) delivered at the same level by three different ventilators on patients' work of breathing (WOB), breathing pattern and gas exchange. DESIGN: Prospective, self-controlled clinical study. SETTING: Intensive care unit of a tertiary university hospital. PATIENTS: Nine intubated adult patients during weaning from mechanical ventilation. INTERVENTIONS: Patients were randomly connected to one of three ventilators: the Siemens Servo 900 C (SC), the Ohmeda CPU 1 (CPU), and the Engström Erica (EE) during both zero cmH2O PSV and 15 cmH2O PSV. MEASUREMENTS AND RESULTS: During zero PSV, there was no significant difference in terms of WOB, VT, VE, or auto-PEEP among the three ventilators, although there was a trend towards higher levels of WOB with EE. During 15 cmH2O PSV, WOB was significantly less with SC than with EE or CPU (0.47 +/- 0.48 J/l for SC, 1.0 +/- 0.48 for EE and 0.78 +/- 0.51 for CPU1, p = 0.003). WOB was 64% less than at zero PSV with SC but only 38% less with EE. This was associated with a different pressurization shape, as assessed by the interior surface of Paw-VT loops (1.23 +/- 0.09 J/l for SC, 0.9 +/- 0.02 for EE, and 0.79 +/- 0.18 for CPU; p < 0.001). At 15 cmH2O PSV, auto-PEEP was significantly lower with SC than with EE (1.7 +/- 2.1 cmH2O for SC, 4.7 +/- 3.6 for EE, and 2.8 +/- 0.3 for CPU; p = 0.04). External expiratory resistances, in cmH2O/l/s, were significantly higher with EE than with CPU or SC (12.9 +/- 3.2 EE, 7.5 +/- 2.4 CPU, 5.9 +/- 0.5 SC; p < 0.001). CONCLUSION: During PSV, the different working principles of different mechanical ventilators profoundly affect patient's WOB. Among the various factors, velocity of pressurization of PSV may play a role in its efficacy in unloading the respiratory muscles.

Acute Disease↗

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗

Comparative effects of pressure support ventilation and intermittent positive pressure breathing (IPPB) in non-intubated healthy subjects.

We compared the efficacy of three devices delivering assisted non-invasive ventilation with different working mechanisms, during room air breathing and during CO2-induced hyperventilation. In seven healthy volunteers, breathing pattern, respiratory muscle activity and comfort were assessed: during unassisted spontaneous breathing through a mouth-piece (SB); during assisted breathing with a device delivering inspiratory pressure support (IPS); and with two devices delivering intermittent positive pressure breathing (IPPB), the Monaghan 505 (IPPB1), and the CPU 1 ventilator (IPPB2). All three devices were set at 10 cmH2O of maximal pressure. During room air breathing, the work of breathing expressed as power, was significantly greater with the two IPPB devices than with the two other modes (IPPB1 and IPPB2 7.3 +/- 5.2 and 7.2 +/- 6.2 J.min-1, respectively, versus SB and IPS 2.4 +/- 0.7 and 2.3 +/- 3.3 J.min-1, respectively). The difference did not reach the statistical significance for the pressure-time product (PTP). Discomfort was also greater during the IPPB modes. During CO2-induced hyperventilation, considerable differences in power of breathing were found between the two IPPB devices and the other two modes. The PTP was also much higher with IPPB. Transdiaphragmatic pressure was significantly smaller during IPS than during the three other modes (IPS 18 +/- 2.6 cmH2O versus SB 22 +/- 2.6, IPPB1 32 +/- 5.2, and IPPB2: 28 +/- 5.2). Maximal discomfort was observed during the IPPB modes and was correlated with the magnitude of transdiaphragmatic pressure (r = 0.60). Despite similarities in their operational principles, IPS and IPPB had very different effects on respiratory muscle activity in healthy non-intubated subjects. IPPB machines not only failed to reduce patient's effort but also induced a significant level of extra work by comparison to spontaneous ventilation at ambient pressure. Great caution is, therefore, needed in the use of patient-triggered devices for non-intubated patients with acute respiratory failure.

Adult↗

Forced oscillation technique vs spirometry to assess bronchodilatation in patients with asthma and COPD.

The forced oscillation technique (FOT) is a noninvasive test used to characterize the mechanical impedance of the respiratory system. The aim of the study was to compare the changes in respiratory conductance (Grs) measured with FOT to those in FEV1 in 22 patients with asthma and 20 patients with chronic obstructive pulmonary diseases (COPD) after salbutamol inhalation. FEV1 and Grs indexes, computed as the ratio of the difference between postbronchodilator and prebronchodilator values over the predicted value, were used to express reversibility of airway obstruction. After inhalation of salbutamol in cumulative doses up to 1,200 micrograms in ten patients of each group, FEV1 and Grs indexes showed parallel changes, and most of the increase was observed after the first dose of 200 micrograms of salbutamol for the two indexes. In all the 42 patients, we found a linear relationship between the two indexes after inhalation of 200 micrograms of salbutamol (r = 0.7, p < 0.0001). We evaluated FEV1 and Grs indexes in terms of sensitivity and specificity for identifying asthmatics among patients with COPD: using a 10% change as the cut-off value, these indexes proved of similar value (sensitivity, 0.91 and 0.95; specificity, 0.95 and 0.85, respectively). We conclude that the use of FOT can be considered as an alternative to forced expiration for detecting bronchodilatation in asthmatics and patients with COPD.

Airway Resistance↗

A synthesis of the Otis, Mead, and Mount mechanical respiratory models.

We propose a unified approach of the viscoelastic models introduced by Otis, Mead and Mount to describe the mechanical behaviour of the respiratory system. A single equation of motion is developed for these two-compartment models and solved in response to typical pressure and volume inputs. The analytic expression of the pressure response to rapid airway occlusion following constant flow inflation, and of the volume response to single breath following end-inspiratory pause are more particularly analysed. The lumped respiratory parameters derived from these responses are expressed as functions of the parameters characterising the constitutive mechanical elements of each model. Different combinations of respiratory models and of methods for measuring respiratory mechanics are examined. For each model, the physiological interpretation of the lumped mechanical parameters is summarised in terms of gas redistribution or tissue viscoelastic properties.

Humans↗

Acute and chronic respiratory effects of sulfur mustard intoxication in guinea pig.

Sulfur mustard (SM) has been used as a vesicant chemical warfare agent. To investigate the respiratory damages it causes, we studied the effects on guinea pigs of an intratracheal injection of 0.3 mg/kg of SM 5 h and 14 days after injection. Five hours after SM intoxication, respiratory system resistance and microvascular permeability were increased. These alterations were not prevented by pretreatment with 50 mg/kg sc of capsaicin 2 wk before SM intoxication. Histological studies showed columnar cell shedding all along the tracheal epithelium, bronchoconstriction, and peribronchial edema. Fourteen days after SM intoxication, guinea pigs demonstrated airway hyperreactivity to aerosolized substance P and histamine. Pretreatment with phosphoramidon caused a further increase in airway responsiveness to substance P. Neutral endopeptidase activity in the tracheal epithelium was decreased by twofold in SM-intoxicated guinea pigs. At this stage, the tracheal epithelium was disorganized and atrophic. These results demonstrate that in guinea pigs SM intoxication induces severe lesions to the tracheal epithelium, which might account for the airway hyperresponsiveness observed 14 days after intoxication.

Acetylcholine↗

Measurement of bronchial responsiveness by forced oscillation technique in occupational epidemiology.

The performance of the forced oscillation technique (FOT) in the assessment of bronchial responsiveness on the methacholine challenge test was compared with that of forced expiratory volume in one second (FEV1) in 119 active workers with normal baseline pulmonary function. Changes in resistance (delta R0%), frequency dependence of resistance (delta P) and resonant frequency (delta F%) determined by the FOT were compared to the delta FEV1%. Receiver operating characteristic (ROC) curves were established to determine values of the changes in FOT parameters which corresponded to the best sensitivity and specificity for classifying the subjects as hyperresponsive or nonresponsive on the methacholine challenge test. Significant correlations were observed between delta FEV1% and delta R0%, delta P and delta F% respectively. The ROC curves showed the following cut-off values of FOT parameters to be the best values for classifying the subjects according to the presence or absence of 20% fall in FEV1: a 65% increase in R0 (sensitivity 75%; specificity: 76%); a decrease of 65 x 10(-3) hPa.l-1.s2 in P (sensitivity 58%; specificity 83%); a 50% increase in F (sensitivity 75%; specificity 62%). Our results suggest that the FOT is a useful test for assessment of bronchial hyperresponsiveness when compared to spirometry, and can be applied to epidemiological studies of a bronchial challenge test in normal active working populations.

Adult↗

Changes in respiratory resistance to low dose carbachol inhalation and to pneumatic trouser inflation are correlated.

Inflation of the leg compartments of pneumatic trousers increases thoracic blood volume. The resultant response in respiratory impedence was investigated in nine normal volunteers, and compared with the response to increasing doses of inhaled carbachol. Respiratory impedance was measured by the forced oscillation technique (4-32 Hz), and respiratory resistance at zero frequency (R0) was extrapolated from linear regression analysis of resistive impedance versus frequency. The mean increase in R0 was 31% after inhalation of 125 micrograms carbachol, and 21% after inflation of pneumatic trousers. The percentage changes in R0 following pneumatic trouser inflation highly correlated those induced by inhalation of 125 micrograms carbachol (r = 0.98) Our data demonstrate that, even in normal subjects, pneumatic trouser inflation causes an increase in respiratory resistance, which can be predicted by the response to a low dose of carbachol. These results support the assumption that cholinergic agents might not only be bronchoconstrictors but also vasodilators of the bronchial vessels. At a low dose, the vasodilating action of carbachol could be the major factor involved in the respiratory response.

Adult↗

Do turbines with servo-controlled speed improve continuous positive airway pressure generation?

Nasal continuous positive airway pressure (CPAP) devices with a servo-mechanism to control pressure have recently been developed. We evaluated six such devices and three conventional systems in terms of effectiveness in maintaining constant pressure. Machines were tested with pressure levels of 5, 10 and 15 cmH2O. Dynamic behaviour was evaluated: 1) by calculating the imposed work of breathing during simulated breath generated by a sinusoidal pump; and 2) by following the fall in pressure after a transient flow of 1 l.s-1. Quasi-static behaviour was evaluated by simulating a predetermined air leak. Under dynamic conditions, work of breathing was lowest with one conventional nasal CPAP device and three servo-controlled nasal CPAP devices; whereas, the highest levels of work of breathing were recorded with two servo-controlled nasal CPAP devices. The pressure-time response to a transient flow yielded similar results, with a significant inverse correlation between pressure values observed after 300 ms and imposed work of breathing during simulated breathing (r = -0.91). Under quasi-static conditions, microprocessor servo-controlled devices exhibited the best performance. These results suggest that microprocessor servo-controlled nasal CPAP devices are not always the best systems for maintaining constant airway pressure in dynamic situations. However, they are more effective in ensuring maintenance of the desired pressure in the event of an air leak at the mask.

Equipment Design↗

Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome.

BACKGROUND: Pressure-controlled (PCV) and pressure-controlled inverse ratio ventilation (PCIRV) have been proposed instead of volume-controlled conventional ratio ventilation (VC) with positive end-expiratory pressure (PEEP) for patients with adult respiratory distress syndrome (ARDS). The advantages advocated with the use of PCIRV are to decrease airway pressures and to improve gas exchange. However, most studies did not compare PCIRV and VC while keeping both the level of ventilation and end-expiratory alveolar pressure (total-PEEP) constant. METHODS: Nine patients with moderate to severe ARDS (lung injury score 2.83 +/- 0.18) had their lungs ventilated with VC, PCV with a conventional ratio (I:E 1:2; PC 1/2), and PCIRV (I:E 2:1 and 3:1; PC 2/1 and PC 3/1, respectively). Ventilator settings were adjusted to keep tidal volume, respiratory rate, FIo2, and total-PEEP constant in every mode. With each mode, a complete set of ventilatory, hemodynamic, and gas exchange parameters was obtained after 30 min. RESULTS: In PC 3/1, the data obtained could not be strictly compared to the other modes because total-PEEP was higher despite external-PEEP being set at zero. For the other modes (VC, PC 1/2, and PC 2/1), despite differences in peak airway pressures, no difference was noted for end-inspiratory and end-expiratory static airway pressures (which better reflect alveolar pressures) nor for lung and respiratory system compliance. Arterial oxygenation deteriorated slightly with PC 2/1 despite a higher mean airway pressure, whereas alveolar ventilation tended to be slightly, but not significantly, improved (lower PaCo2). A decrease in systolic and mean arterial pressure also was observed with PC 2/1 without other significant hemodynamic change. CONCLUSIONS: In this prospective controlled study, no short-term beneficial effect of PCV or PCIRV could be demonstrated over conventional VC with PEEP in patients with ARDS.

Adult↗

Measurement of respiratory impedance by forced oscillation: comparison of the standard and head generator methods.

Physiological and clinical studies have shown that the standard method of measuring respiratory impedance by forced oscillation leads to less efficient control of the upper airway shunt effect than the head generator method. To test the effects of these two techniques in epidemiological studies, we compared, in a sample of 73 French agricultural workers, the values obtained with each method for five forced oscillation parameters: resistance, frequency dependence of resistance, inertance, compliance and resonant frequency. For these comparisons, subjects were classified according to four respiratory status factors: smoking status, cough, expectoration and airway obstruction assessed from the maximum expiratory flow volume curve. Logistic regression models using the set of four forced oscillation parameters (excluding resonant frequency, which is derived from compliance and inertance) were then used to analyse the ability of each method to classify the subjects in each group. Significant differences between the two methods were observed for the mean values obtained for all five parameters. However, when each parameter was considered separately, the correlations between the values for each method were significant. Each method possessed the necessary ability to separate subjects into our group classification, but the significant relationships were not always found for the same parameters. Finally, logistic regression models showed that the two methods led to almost the same classification of the subjects. According to our results, the standard method of applying forced oscillation at the mouth seems an acceptable device for measuring respiratory impedance for epidemiological purposes.

Airway Obstruction↗

Influence of signal processing on estimation of respiratory impedance.

Respiratory impedance was estimated between 4 and 30 Hz by spectral analysis of the mouth flow and pressure signals measured in spontaneously breathing subjects when applying a pseudorandom pressure excitation at the mouth. The signals were submitted to antialiasing low-pass filtering followed by digital preprocessing before the calculation of spectra by a fast Fourier transform algorithm. The effectiveness of signal preprocessing in eliminating the leakage error due to breathing noise was illustrated in both a mechanical analogue and a patient. Five preprocessing techniques that combined high-pass filtering and windowing were then compared in 32 randomly selected patients by examining the influence of these techniques on 1) the values of impedance at 5, 10, and 20 Hz, and 2) the parameters of linear models fitting the real (Zr) and imaginary (Zi) parts of impedance for coherence values higher than a preset threshold. The impedance values and derived parameters were either the mean of the estimates separately obtained in the three data recordings (PA) or the single estimate obtained from average spectra (SP). Small but significant differences between filtering and windowing, as well as between SP and PA, were evidenced for the Zr, whereas Zi was only slightly sensitive to the type of averaging technique. We conclude that the signal preprocessing and data averaging techniques selected in this study have similar effects on spectral estimation of respiratory impedance.

Airway Resistance↗

Involvement of tachykinins in pentamidine-induced airway constriction and microvascular leakage in the guinea pig.

We investigated the effects of aerosolized pentamidine isethionate on airway constriction and microvascular leakage in the guinea pig, and the role of tachykinins in these abnormalities. The bronchoconstrictor response to pentamidine was determined in anesthetized, tracheotomized and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized pentamidine (5 to 30 mg/ml; 60 breaths). Respiratory system resistance was measured by the occlusion method. Airway microvascular permeability was evaluated by measuring the Evans blue dye concentration in the trachea and main bronchi. Aerosolized pentamidine caused a concentration-related increase in respiratory system resistance that was prevented by pretreatment with 50 mg/kg capsaicin given subcutaneously 2 wk before pentamidine and was significantly reduced by pretreatment with 1 mg/kg morphine given intravenously. Pretreatment with 10(-4) M aerosolized phosphoramidon (90 breaths) significantly enhanced the bronchoconstrictor response to pentamidine. Aerosolized pentamidine (50 mg/ml; 90 breaths) increased airway microvascular permeability, as the Evans blue dye concentration was 72.6 +/- 3.7 ng/mg tissue in guinea pigs aerosolized with pentamidine versus 34.2 +/- 3.5 ng/mg tissue in the controls. Capsaicin pretreatment inhibited the increase in microvascular leakage induced by pentamidine. Pretreatment with 5 mg/ml aerosolized albuterol (90 breaths) prevented the bronchoconstrictor response to pentamidine but failed to prevent the pentamidine-induced increase in microvascular permeability. Atropine did not modify the bronchoconstrictor response to pentamidine. These results indicate that in the guinea pig, pentamidine isethionate induces bronchoconstriction and airway microvascular leakage, which are mediated by tachykinins released from sensory nerves. Albuterol, which is used in humans to prevent bronchoconstriction, does not seem able to prevent airway edema.

Aerosols↗