Volume dependence of respiratory system resistance during artificial ventilation in rabbits.

The volume dependence of respiratory resistance (Rrs), usually observed during normal breathing, is expected to be accentuated during expiratory flow limitation (EFL). In order to quantify this dependence we studied the pressure, flow, and volume data obtained from eight New Zealand rabbits, artificially ventilated at different levels of applied expiratory pressure (0-10 hPa), before and during histamine i. v. infusion. EFL was provoked by lowering the expiratory pressure and was detected by the application of an additional negative expiratory pressure and by forced oscillations. The analysis of respiratory system mechanics was performed by multiple regression, using the classical linear first-order model and also a nonlinear model, accounting for volume dependence of Rrs. Both models satisfactorily fitted the data in the absence of EFL. The nonlinear model proved to be more appropriate in the presence of EFL. The coefficient expressing the volume dependence of Rrs (Rvd) was significantly more negative during EFL. Rvd values were highly correlated with the fraction of the tidal volume left to be expired at the onset of EFL. A threshold Rvd value of -1,000 (hPa x s x l(-2)) detected EFL with high sensitivity and specificity. We conclude that a strongly negative volume dependence of Rrs is a reliable and noninvasive index of EFL during artificial ventilation.

Evaluation of a method for assessing respiratory mechanics during noninvasive ventilation.

Noninvasive assessment of respiratory resistance (Rrs) and elastance (Ers), which is not easy with conventional methods, could be useful in the optimization of pressure support ventilation. The aim of this study was to evaluate a simple noninvasive method (Delta-inst) of measuring Rrs during nasal pressure support ventilation. Rrs and Ers (Delta-inst) were computed from inspiratory mask pressure, flow and volume recorded during pressure support ventilation. The Delta-inst method was compared with the forced oscillation technique (FOT) in seven patients with chronic obstructive pulmonary disease (COPD) and in eight healthy subjects without and with added resistance (3.1 cmH2O x s x L(-1)). Rrs measured by Delta-inst (5.2+/-1.7, 7.2+/-0.5 and 6.9+/-1.2 cmH2O x s x L(-1)) and by FOT (5.0+/-0.7, 7.6+/-0.9 and 8.1+/-2.7 cmH2O x s x L(-1)) in healthy subjects without and with added resistance and COPD, respectively, were not significantly different (p>0.05). Rrs measured by both techniques showed a significant coefficient of linear correlation (r=0.70 s) (p<0.01). In the COPD patients, the variability of Delta-inst Rrs (30%) was greater than that of FOT Rrs (21%). The agreement between Ers obtained by Delta-inst and by FOT was less than that found for Rrs. Delta-inst is a noninvasive and simple method for reliably assessing resistance. Therefore, it is useful for monitoring airway obstruction and is potentially helpful in adapting the settings for pressure support ventilation in accordance with patient mechanics.

Respiratory and upper airways impedance responses to methacholine inhalation in spontaneously breathing cats.

The upper airways may contribute to the increase in respiratory resistance induced by methacholine (Mch). The aim of this study was to simultaneously assess the Mch response of upper airways and lower respiratory resistances (Rua, Rrs,lo) and reactances (Xua, Xrs,lo), and to test whether the change of total respiratory resistance and reactance after Mch were affected by upper airways mechanisms. Seven cats breathing spontaneously were studied under chloralose, urethane anaesthesia. Forced oscillations were generated at 20 Hz by a loud-speaker connected to the pharyngeal cavity. A pneumotachograph was placed between rostral and caudal extremities of the severed cervical trachea. Pressure drops were measured across the upper airways and across the lower respiratory system. Rua, Xua, Rrs,lo and Xrs,lo were obtained after nebulized normal saline and Mch administered directly through the tracheostomy. The analysis focused on Mch tests showing clear positive upper airways response. Volume and flow dependence of Rrs,lo and Rua were assessed during tidal inspiration using multiple linear regression analysis. After Mch, Rrs,lo increased and became negatively volume dependent, while the increase in Rua was associated with no significant change in volume dependence; Xrs,lo became negative while Xua did not change. The upper airways response to methacholine may thus contribute to the increase in total respiratory resistance but may not account for either its negative volume dependence or the decrease in total resistance. It is surmised that these features more specifically reflect alterations in respiratory mechanics occurring at the level of the intrathoracic airways.

A simplified method for monitoring respiratory impedance during continuous positive airway pressure.

The forced oscillation technique is useful in detecting changes in upper airway obstruction in patients with sleep apnoea undergoing continuous positive airway pressure (CPAP) ventilation. The aim of this study was to implement and evaluate a method for estimating respiratory impedance (Zrs) from the pressure and flow recorded at the inlet of the CPAP tubing. The method is based on correcting impedance measured at the inlet of the CPAP tubing (Zi) for the effect of the tubing and the exhalation port. The method was evaluated in mechanical analogues and in a healthy subject. Sinusoidal oscillation of 5, 10 and 20 Hz were superimposed on CPAP (5-15 cmH2O). At 5 Hz, the changes in airflow obstruction were substantially underestimated by Zi. Furthermore, Zi exhibited a negative dependence on Zrs at 20 Hz. The assessment of Zrs was greatly improved after correcting Zi for the effects of the CPAP tubing and the exhalation port. Zrs was well estimated at low frequencies, reaching very high values during total occlusion (>60 cmH2O x s x L(-1) at 5-10 Hz). These results indicate that changes in airflow obstruction can be detected using the forced oscillation technique from pressure and flow recorded on the continuous positive airway pressure device. This facilitates the clinical application of the forced oscillation technique for monitoring upper airway patency during sleep.

Methacholine-induced volume dependence of respiratory resistance in preschool children.

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2¿V'¿+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.

Partitioning of respiratory mechanical impedance by absolute and differential body plethysmography.

We have recently demonstrated the feasibility of partitioning total respiratory impedance (Zrs) into its airway (Zaw) and tissular (Zti) components by measuring alveolar gas compression (Vpl) plethysmographically during pressure oscillations at the airway opening (Peslin et al.). The aim of this study was to comparatively evaluate an alternative approach: the measurement of Zrs and of the transfer function (FTF) between airway flow and body surface flow obtained by absolute body plethysmography. The two approaches are theoretically equivalent, provided thermal and other artifacts are properly eliminated. Zrs and Vpl (method 1) and Zrs and FTF (method 2) were measured in 11 healthy subjects from 4 to 29 Hz, using a pressure-type and a flow-type plethysmograph, respectively. Inspired gas was conditioned to body temperature and pressure, saturated with water vapor in both instances to minimize thermal factors. Zaw and Zti spectra computed from both sets of data were quite similar in shape. Neither airway resistance nor tissue compliance differed significantly; tissue resistance, however, was about 14% lower with method 1, which may be due to imperfect gas conditioning. The reproducibility of the data was similar with the two approaches. We conclude that absolute body plethysmography is as reliable as differential body plethysmography to partition Zrs.

Removal of thermal artifact in alveolar pressure measurement during forced oscillation.

Thoracic gas volume (TGV) may be measured and total respiratory impedance (Zrs) may be partitioned into its airway and tissue (Zti) components by combining forced oscillations and plethysmographic measurements of alveolar gas compression (Vpl) (Peslin, Duvivier, 1998, J. Appl. Physiol. 84, 553-561 and 862-867). The method requires that the thermal component of Vpl (Vpl,th) be eliminated by conditioning inspired gas to BTPS. We have evaluated a technically simpler method where Vpl,th is corrected using a thermal gain (G) and a thermal time constant (theta). Zrs and the relationship between Vpl and flow (Hpl) were measured in 15 healthy subjects at frequencies from 4 to 29 Hz. G was obtained from the breathing component of Vpl in phase with volume. Zti and TGV (TGVos) were computed from Zrs and from Hpl after the latter was corrected using G and different values of theta. With theta = 27.5 ms both the difference between TGVos and standard plethysmographic TGV, and the difference between Zti spectra obtained with and without gas conditioning were minimal. We conclude that the simpler method is adequate for both purposes.

Forced oscillation total respiratory resistance and spontaneous breathing lung resistance in COPD patients.

Forced-oscillation total respiratory resistance (Rrs) has been shown to underestimate spontaneous breathing lung resistance (RL,sb) in patients with airway obstruction, probably owing to upper airway shunting. The present study reinvestigates that relationship in seven severely obstructed chronic obstructive pulmonary disease patients using a technique that minimizes that artefact. Rrs at 8 and 16 Hz was computed for each successive forced oscillation cycle. Inspiratory and expiratory RL,sb were obtained by analysing transpulmonary pressure (Ptp) with a four-coefficient model, and compared to Rrs over the same periods. "Instantaneous" values of RL,sb were also obtained by computing the dynamic component of Ptp, and compared to simultaneous values of Rrs. In both respiratory phases, good agreement between Rrs and RL,sb was observed up to RL,sb values of approximately 15 hPa x s(-1) x L(-1) at 8 Hz and 10 hPa x s(-1) x L(-1) at 16 Hz. Instantaneous Rrs and RL,sb varied systematically during the respiratory cycle, exhibiting various amounts of flow- or volume-dependence in the seven patients; the amplitudes of their variations were significantly correlated, but Rrs was much more flow-dependent than RL,sb in three patients. Also, Rrs exceeded RL,sb at end-expiration in three instances, which could be related to expiratory flow limitation. In conclusion, total respiratory resistance is reliable up to much higher levels of airway obstruction than previously thought, provided upper airway shunting is avoided.

Reliability of thoracic gas volume derived from mechanical impedance at different levels of the vital capacity.

BACKGROUND: Thoracic gas volume (TGV) may be estimated during spontaneous breathing by measuring simultaneously respiratory impedance (Zrs) and alveolar gas compression (Vpl) at several oscillation frequencies [Peslin and Duvivier: J Appl Physiol 1998;84:862-867]. OBJECTIVE: The aim of the study was to test the validity of that approach at different levels of the vital capacity (VC). METHODS: We measured Zrs and Vpl at frequencies ranging from 6 to 29 Hz in 10 healthy subjects rebreathing BTPS gas in a constant volume body plethysmograph. In a first series, the subjects were asked to breathe voluntarily at different levels of the VC and oscillation TGV (TGVos) was compared to standard plethysmographic TGV (TGVst) assessed immediately after TGVos measurements. In a second series, the subjects were asked to change stepwise their lung volume in the middle of the forced oscillation recording, and the changes in TGVos (DeltaTGVos) were compared to the changes in lung volume (DeltaV) computed from the integrated flow signal. RESULTS: In most subjects TGVos and TGVst were highly correlated and the slopes of the relationships did not differ significantly from unity. DeltaTGVos and DeltaV were also highly correlated both in individuals and in the group (r = 0.97), and their signless differences averaged 0.23 +/- 0.20 liter. CONCLUSION: We conclude that forced oscillation estimates of TGV are reliable in healthy subjects over a large part of the VC.

Assessment of bronchial reactivity by forced oscillation admittance avoids the upper airway artefact.

The forced oscillation technique (FOT) allows easy assessment of bronchial reactivity. The use of a standard FOT generator (SG) results in changes in respiratory system resistance (delta Rrs,SG) which are affected by an artefact caused by the extrathoracic upper airway (EUA). The aim was to improve the FOT assessment of bronchial reactivity with the SG by computing the change in FOT admittance (delta Ars,SG), which is theoretically unaffected by this artefact. Delta Rrs,SG and delta Ars,SG after bronchial challenge in 17 children were compared with the values measured with a head generator (HG) FOT setup (delta Rrs,HG and delta Ars,HG, respectively), which were taken as a reference, since HG provides data virtually freed from the EUA artefact. At 10 Hz, the SG significantly underestimated the resistance change: delta Rrs,SG=1.77+/-0.62 versus delta Rrs,HG=6.09+/-1.23 hPa x L(-1) x s. Delta Rrs,SG and delta Rrs,HG did not show a significant correlation. By contrast, the amplitude of the change in admittance measured by SG was close to the one obtained with the reference HG: /delta Ars,SG/=29.5+/-4.6 versus /delta Ars,HG/=32.7+/-3.9 mL x hPa(-1) x s(-1). /Delta Ars,SG/ and /delta Ars,HG/ showed a significant correlation (r=0.65, p>0.01). Similar results were found up to 20 Hz. The extrathoracic upper airway artefact was minimized when computing the change in admittance with the standard generator. This forced oscillation technique index may improve the sensitivity in assessing bronchial reactivity with the standard generator setup, which is the most common and easiest to use method for routine lung function testing.

Dose-response slope of forced oscillation and forced expiratory parameters in bronchial challenge testing.

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 microg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20) or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or = 20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%, Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.

Flow-dependent positive airway pressure to maintain airway patency in sleep apnea-hypopnea syndrome.

Airway obstruction in patients with sleep apnea-hypopnea syndrome (SAHS) is due to increased critical pressure (Pcrit) of the upper airway. The ideal nasal pressure (Pn) to maintain airway patency should consist of the constant term to account for Pcrit and a term (Rn . V) proportional to flow (V) to account for the dynamic pressure drop through nasal resistance (R n). Continuous positive airway pressure (CPAP) applied to avoid flow limitation results in a Pn greater than required over most of the breathing cycle. The aim was to assess a flow-dependent positive airway pressure (FDPAP) based on adapting Pn to the instantaneous flow: Pn = P0 + k . V. FDPAP was tested on collapsible airway models and its applicability was assessed in nine patients with SAHS during sleep. In models, FDPAP prevented flow limitation with lower mean P n and work of breathing than CPAP. In patients FDPAP allowed the patients to breathe normally with a mean Pn (6.6 +/- 1.2 cm H2O) systematically and significantly (p < 0.05, paired t test) lower than when applying CPAP (9.1 +/- 1.2 cm H2O). The results found in models and in patients suggest that adapting the applied nasal pressure to the instantaneous breathing flow may be of potential practical interest in SAHS.

Reproducibility of lung volume measurements.

Test reproducibility is an important consideration when interpreting results and should be set as a goal during data collection. Reproducibility criteria may need to be different for different subject groups and are instrument and procedure-dependent. Ideally, the within-subject variability for each lung volume and measurement technique used should be established for each laboratory. These values also need to be established for each different subject group (age and disease). At a minimum, test reproducibility should be monitored and controlled and each laboratory should define their between-day reproducibility of measurements on at least one "reference" subject from ongoing periodic (e.g., weekly or monthly) measurements as part of their laboratory's quality control programme. For plethysmographic measurements functional residual capacity (FRC)pleth multiple determinations and a corresponding test reproducibility criteria is probably justified.

Evaluation of a forced oscillation method to measure thoracic gas volume.

The purpose of this study was to test a plethysmographic method of measuring thoracic gas volume (TGV) that, contrary to the usual panting method, would not require any active cooperation from the subject. It is based on the assumption that the out-of-phase component of airway impedance varies linearly with frequency. By using that assumption, TGV may be computed by combining measurements of total respiratory impedance (Zrs) and of the relationship between the plethysmographic signal (Vpl) and airway flow (V) during forced oscillations at several frequencies. Zrs and Vpl/V were measured at 10 noninteger multiple frequencies ranging from 4 to 29 Hz in 15 subjects breathing gas in nearly BTPS conditions. Forced oscillation measurements were immediately followed by determination of TGV by the standard method. The data were analyzed on different frequency ranges, and the best agreement was seen in the 6- to 29-Hz range. Within that range, forced oscillation TGV and standard TGV differed little (3.92 +/- 0.66 vs. 3.83 +/- 0.73 liters, n = 77, P < 0.05) and were strongly correlated (r = 0.875); the differences were not correlated to the mean of the two estimates, and their SD was 0.35 liter. In seven subjects the differences were significantly different from zero, which may, in part, be due to imperfect gas conditioning. We conclude that the method is not highly accurate but could prove useful when, for lack of sufficient cooperation, the panting method cannot be used. The results of computer simulation, however, suggest that the method would be unreliable in the presence of severe airway inhomogeneity or peripheral airway obstruction.

Respiratory oscillation mechanics in infants with bronchiolitis during mechanical ventilation.

The aim of the study was to describe the pattern of respiratory oscillation mechanics and responses to positive end-expiratory pressure (PEEP) in bronchiolitis. Six infants were studied during the course of mechanical ventilation. A 20 Hz sinusoidal pressure variation was applied at the endotracheal tube where flow was measured with a pneumotachograph. Resistance and reactance obtained from the complex pressure-flow ratio were separated during inspiration (R(rs,i); X(rs,i)) and expiration (R(rs,e); X(rs,e)), and the differences between R(rs,i) and R(rs,e) (deltaR(rs)) and X(rs,i) and X(rs,e) (deltaX(rs)) were calculated. The data were corrected for the mechanical characteristics of the endotracheal tube. The measurements were repeated while PEEP was varied between 0 and 8 hPa. Two infants were found to have normal R(rs) and near-zero X(rs) and both parameters exhibited little change within the respiratory cycle or with varying PEEP. Four infants had high R(rs) at zero PEEP. In two, R(rs,i) was markedly elevated (108.5 and 85.2 hPa.s/L, respectively), and X(rs,i) was markedly negative (-25.0 and -22.5 hPa.s/L, respectively) at zero PEEP, while deltaR(rs) and deltaX(rs) were small. R(rs,i) and the absolute value of X(rs,i) decreased with increasing PEEP. This pattern of oscillation mechanics was consistent with low lung volumes and atelectasis, being reversed by increasing PEEP. In the remaining two subjects, R(rs,i) was moderately elevated (57.8 and 53.6 hPa.s/L, respectively) and X(rs,i) moderately negative (-12.5 and -7.7 hPa.s/L, respectively) at zero PEEP. DeltaR(rs) (-59.8 and -56.5 hPa.s/L, respectively) and delta(rs) (28.1 and 48.7 hPa.s/L, respectively) were large, but were dramatically reduced by increasing PEEP. These patterns were consistent with expiratory airflow limitation. Measurements of respiratory impedance are, therefore, informative in regard to the pathophysiological mechanisms occurring in bronchiolitis during mechanical ventilation, and they may be helpful in setting the level and assessing the effect of PEEP.

Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography.

We have tested the feasibility of separating the airway (Zaw) and tissue (Zti) components of total respiratory input impedance (Zrs,in) in healthy subjects by measuring alveolar gas compression by body plethysmography (Vpl) during pressure oscillations at the airway opening. The forced oscillation set up was placed inside a body plethysmograph, and the subjects rebreathed BTPS gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zaw and Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gas volume. The data were in good agreement with previous observations: airways and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 +/- 0.003 hPa.s2.l-1 and tissue reactance with an elastance of 36 +/- 8 hPa/I. The changes seen with varying lung volume, during elastic loading of the chest and during bronchoconstriction, were mostly in agreement with the expected effects. The data, as well as computer simulation, suggest that the partitioning is unaffected by mechanical inhomogeneity and only moderately affected by airway wall shunting.

Variations in airways impedance during respiratory cycle derived from combined measurements of input and transfer impedances.

Simultaneous measurement of input (Zin) and transfer impedances (Ztr) allows separation of airway and tissue properties at a single frequency, without making assumptions concerning the structure of the two compartments. This approach offers the possibility of studying the variation in airway impedance (Zaw) during the respiratory cycle. Zin and Ztr were measured at frequencies of 10, 20, 30 and 40 Hz in eight healthy subjects to study the variations in Zaw according to a modification of the Rohrer's equation: X=K1+K2(V'ao)-K3V, where V is volume and V'ao the flow at the airway opening. The results showed that Zaw could be modelled as a simple resistance-inertance pathway. Variations in airway resistance (Raw) with flow were greater during expiration than during inspiration with K2 values varying from 0.76-0.90 hPa x s2 x L(-2) during inspiration and 0.84-1.47 hPa x s2 x L(-2) during expiration, independently of frequency. Raw was negative volume dependent; it decreased more with increasing volume during inspiration than during expiration. Airways inertance calculated from the imaginary part of Zaw also underwent systematic variations during the respiratory cycle, but, in contrast to Raw, flow dependence was negative during both phases. In conclusion, the approach used in this study allows flow and volume dependencies of airways mechanical properties to be studied and can also provide indices of airway patency independently of flow, which is of great potential interest for studying variations in airway resistance during bronchomotor tests.

Vasodilators, aortic elasticity, and ventricular end-systolic stress in nonanesthetized unrestrained rats.

We evaluated the effect of different vasodilators on ventricular end-systolic stress by investigating the impact of sodium nitroprusside, nifedipine, and hydralazine on blood pressure, aortic stiffness, and wave reflection during drug-induced hypotension (to 80 mm Hg mean blood pressure) in normotensive (central aortic mean blood pressure, 116 to 119 mm Hg; systolic pressure, 133 to 137 mm Hg), nonanesthetized, unrestrained rats. Aortic stiffness was evaluated from the slope of the linear regression relating pulse wave velocity (PWV) to central aortic mean or pulse pressure. The fall in central aortic systolic blood pressure was less than the fall in mean pressure, especially after hydralazine (122+/-4 mm Hg; sodium nitroprusside, 107+/-2; and nifedipine, 112+/-3 mm Hg; P<.05). The PWV/mean pressure slope was linear, positive, and similar in all three groups (hydralazine, 3.3+/-0.2; sodium nitroprusside, 3.8+/-0.3; and nifedipine, 3.9+/-0.3 cm x s[-1]x mm Hg[-1]; P>.05). The PWV/pulse pressure slope was linear, negative, and less steep in the case of hydralazine (-4.9+/-0.6; sodium nitroprusside, -15.5+/-3.7; and nifedipine, -13.5+/-2.9 cm x s[-1] x mm Hg[-1]; P<.05). The travel time and augmentation index of the reflected wave were similar in all groups. In conclusion, sodium nitroprusside and nifedipine had a more beneficial effect on end-systolic stress than did hydralazine. This does not appear to be related to any specific effect on wave reflection or the "static" relationship between PWV and aortic mean blood pressure; it may be related to the effects of these drugs on the "dynamic" relationship between PWV and pulse pressure.

Effect of the inhibitor of NO synthase, NG-nitro-L-arginine methyl ester, on histamine-induced bronchospasm in the rabbit.

New Zealand male rabbits were anaesthetized with thiopental, tracheotomized, curarized by vecuronium bromide and mechanically ventilated. Six rabbits received L-NAME 10 mg kg-1 i.v., six rabbits L-NAME 15 mg kg-1 iv, and six rabbits received saline i.v. (controls), 5 min before a histamine aerosol (2% solution during 5 min). Six others rabbits received an injection of L-NAME 15 mg kg-1 iv, 5 min before the histamine aerosol, followed by an infusion of L-arginine over a 60- min period. Total respiratory resistance (Rrs) and elastance (Ers) were derived by least square analysis of the relationship between tracheal pressure and flow, and computed every minute before and over a 1-h period after the histamine aerosol. Oxygen free radicals (OFR) were measured with a luminometer, in microsomes from lung homogenates at the end of the experiment. Compared with the histamine response of the control group, the Rrs response in the L-NAME 10 group was slightly less, while Ers changes were the same in the two groups. In contrast, L-NAME 15 was responsible for an increased Rrs response, the difference being significant (P < 0.05) only between 15 and 40 min after the aerosol (+114% vs. +85% in controls at the 20th min). The increase in Ers with L-NAME 15 was stronger and significantly larger (+71% vs. +42% in controls at the 20th min after the histamine aerosol, P < 0.001). The relatively greater effect of L-NAME on Ers than on Rrs suggests that NO predominantly modulates the response to histamine of the peripheral lung rather than that of the large airways. Furthermore, the effect of L-NAME on Rrs was completely abolished by L-arginine, while its effect on Ers was only partially reversed. This suggests that the changes in Ers are partly related to a hardly reversible phenomenon. Possibly, the mechanical changes are linked with the rise of OFR in the lung parenchyma, which were significantly higher in the L-NAME 15 group compared to the control group (P < 0.05).