C. Duvivier

Calcification of Medial Elastic Fibers and Aortic Elasticity

We tested the hypothesis that a simple change in wall composition (medial calcium overload of elastic fibers) can decrease aortic elasticity. Calcium overload was produced by hypervitaminosis D plus nicotine (VDN) in the young rat. Two months later, measurement of central aortic mean blood pressure in the unanesthetized, unrestrained rat showed that the VDN rat suffered from isolated systolic hypertension but that mean blood pressure was normal. Wall thickness and internal diameter determined after in situ pressurized fixation were unchanged, as was calculated wall stress. Wall stiffness was estimated from (1) elastic modulus (determined with the Moens-Korteweg equation and values for aortic pulse wave velocity in the unanesthetized, unrestrained rat and arterial dimensions) and (2) isobaric elasticity (= slope relating pulse wave velocity to mean intraluminal pressure in the phenylephrine-infused, pithed rat preparation). Both increased after VDN, and both were significantly correlated to the wall content of calcium and the elastin-specific amino acids desmosine and isodesmosine. Left ventricular hypertrophy occurred in the VDN model, and left ventricular mass was related to isobaric elasticity. In conclusion, elastocalcinosis induces destruction of elastic fibers, which leads to arterial stiffness, and the latter may be involved in the development of left ventricular hypertrophy in a normotensive model.

A correction procedure for the asymmetry of differential pressure transducers in respiratory impedance measurements

The usual setup for measuring respiratory input impedance requires a differential pressure transducer attached to a pneumotachograph. Because no data correction procedure has been devised to account for transducer asymmetry, a highly symmetrical transducer is required to obtain reliable impedance data. Here, a general model for the measuring system is presented. Its main feature is that differential pressure transducers are modeled as two-input-one-output systems. From the theoretical model, a dynamic calibration and data correction procedure is defined. This was tested using highly asymmetrical transducers (common-mode rejection ratio between 45 and 27 dB) to measure the impedance of two respiratory analogs. Results obtained show that respiratory input impedance can be adequately measured if data are corrected for transducer asymmetry.<<ETX>>

Expiratory flow limitation during mechanical ventilation detected by the forced oscillation method

We have previously observed large phasic variations of respiratory mechanical impedance in chronic obstructive pulmonary disease (COPD) patients mechanically-ventilated for acute respiratory failure, and postulated that they were due to expiratory flow limitation (EFL). The aim of this study was to test that assumption experimentally and to assess the value of impedance for automatic and noninvasive detection of EFL during mechanical ventilation. The study was performed: 1) in a mechanical analogue, including a flow-limiting element; and 2) in eight anaesthetized and paralysed rabbits, before and during histamine infusion. In both instances, EFL was obtained by lowering the expiratory pressure, using a computer-controlled ventilator; the absence of flow increase when expiratory pressure was further lowered was taken as evidence of EFL. Impedance was measured by applying 15 Hz oscillations at the airway opening. Its real (Re) and imaginary (Im) parts were measured separately during the inspiratory and the expiratory phases, and their differences were related to the mean inspiratory modulus. With the analogue, EFL was accompanied by large decreases both of Re and Im during the expiratory phase. In the rabbits, phasic variations of Re were variable in sign and were not significantly different with and without EFL. In contrast, EFL systematically and specifically decreased Im during the expiratory phase. A threshold of -50% provided a sensitivity of 96% and a specificity of 100% for detecting EFL. The observed phasic variations may be explained by airway wall shunt properties. The study suggests that a large decrease of the imaginary part of impedance during the expiratory phase is a sensitive and specific index of expiratory flow limitation during artificial ventilation.

Frequency dependence of specific airway resistance in a commercialized plethysmograph

Specific airway resistance (sRaw) measured by body plethysmography has been shown to decrease markedly with decreasing breathing frequency when the inspired air is not conditioned to body temperature, atmospheric pressure and saturation with water vapour (BTPS). The phenomenon has been attributed to noninstantaneous gas warming and wetting in the airways. The aim of this investigation was to assess whether the phenomenon was also present in a commercialized plethysmograph featuring an electronic BTPS correction. Airway resistance (Raw) and sRaw were measured in 15 healthy subjects at six breathing frequencies ranging 0.25-3 Hz, using a constant volume plethysmograph in which a correction for non-BTPS gas conditions was applied by electronically flattening the box pressure-airway flow loop (Jaeger Masterscreen Body, version 4.0). The temperature and water vapour saturations in the box averaged 26.5 +/- 1.3 degrees C and 59 +/- 6%, respectively. Raw and sRaw exhibited a clear positive frequency dependence in all but one subject. From 0.25 to 3 Hz Raw increased from (mean+/-SD) 0.62 +/- 0.55 to 1.71 +/- 0.76 hPa x s x L-1 (p<0.001), and sRaw from 2.34 +/- 1.90 to 7.55 +/- 3.08 hPa x s (p<0.001). The data are consistent with a simple model, in which gas conditioning in the airways and external dead space occurred with a time constant of 0.39 s. We conclude that the electronic BTPS correction of the instrument was inadequate, probably because it is assumed that gas conditioning in the airways is instantaneous. We recommend that, with similar instruments, airway resistance be measured using as high a panting frequency as feasible.

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 Rohrers equation: X=K1+K2(Vao)-K3V, where V is volume and Vao 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.

Fourier analysis versus multiple linear regression to analyse pressure-flow data during artificial ventilation

Respiratory resistance (Rrs) and elastance (Ers) are commonly measured in artificially-ventilated patients or animals by multiple linear regression of airway opening pressure (Pao) versus flow (V) and volume (V), according to the first order model: Pao = P0 + Ers.V + Rrs.V, where P0 is the static recoil pressure at end-expiration. An alternative way to obtain Rrs and Ers is to derive them from the Fourier coefficients of Pao and V at the breathing frequency. A potential advantage of the second approach over the first is that it should be insensitive to a zero offset on V and to the corresponding volume drift. The two methods were assessed comparatively in six tracheotomized, paralysed and artificially ventilated rabbits with and without adding to V an offset equal to 5% of the mean unsigned flow. The 5% flow offset did not modify the results of Fourier analysis, but increased Rrs and Ers from linear regression by 15.8 +/- 4.6% and 4.55 +/- 0.64%, respectively. Without additional offset, differences between the two methods averaged 30.2 +/- 14.0% for Rrs and 9.3 +/- 6.2% for Ers. The differences almost completely disappeared (2.47 and 0.61%, respectively) when the flow signal was zero-corrected using the assumption that inspired and expired volumes were the same. After induced bronchoconstriction, however, Ers was still slightly larger by linear regression than by Fourier analysis, which may result from nonlinearities and/or frequency dependence of the parameters. We conclude that the regression method requires zero flow correction and that Fourier analysis is an attractive alternative.

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.

Changes in inspired gas composition and experimental bronchospasm in the rabbit.

In clinical practice, bronchospasm could be facilitated by hypoxia and by hypercapnia. In this study we assessed the influence of breathing a hypoxic (FIO2 = 0.10) or a hypercapnic (FICO2 = 0.08) gas mixture on the response to nebulized histamine (2% solution for 5 min) in anesthetized, tracheotomized, paralyzed and mechanically ventilated rabbits. Total respiratory resistance (Rrs) and elastance (Ers) were derived by least-square analysis from the relationship between tracheal pressure and flow. Control values of Rrs were larger during hypoxia and hypercapnia than in air while the values of Ers were similar. The absolute change in Rrs after histamine was similar in air and hypoxia, and larger in hypercapnia. The relative change, however, was smaller in hypoxia than in the two other conditions. Ers was also substantially increased by histamine and, contrary to Rrs, remained high 60 min after the aerosol. The results suggest: (1) that both hypoxia and hypercapnia increase airway resistance but do not change tissue properties; (2) that the response to histamine is depressed by hypoxia; (3) that a substantial part of the immediate response, and most, if not all, of the residual response after 60 min is due to changes in lung tissue viscoelastic properties.

Separation of airway and tissue properties by transfer respiratory impedance and thoracic gas volume in reversible airway obstruction.

The aim of this study was to establish the ability to estimate separate airway and tissue properties from transfer respiratory impedance (Zrs,tr) data in the presence of airway obstruction. Zrs,tr, thoracic gas volume (TGV) and airway resistance (Raw,pleth) were measured in the presence of obstruction and after use of a bronchodilator (BD) in 13 normal or asymptomatic asthmatic adults and 28 children with symptomatic asthma. An analytical approach was used to solve the equations of a simplified variant of DuBois model, including airway resistance (Raw*) and inertance (Iaw), tissue compliance (Ct) and resistance (Rt) and pulmonary gas compliance (Cg). The equations of the model could not be reliably solved in four children before BD. Mean Raw,pleth was not different from mean Raw* in adults before (mean +/- SEM) (3.4 +/- 0.5 vs 3.1 +/- 0.3 hPa.s.L-1) or after BD (1.4 +/- 0.2 vs 1.8 +/- 0.2 hPa.s.L-1), or in children after BD (2.9 +/- 0.3 vs 3.2 +/- 0.2 hPa.s.L-1, respectively). In children before BD, Raw* was significantly underestimated compared with Raw,pleth (3.8 +/- 0.4 vs 5.4 +/- 0.6 hPa.s.L-1). Overall, a significant positive correlation was found between the difference [Raw,pleth - Raw*] and Raw,pleth (r = 0.82). In adults, BD induced a decrease in Raw* and Rt, an increase in Ct, and no change in Iaw. In children after BD, there was no significant change in Raw* or Ct, whilst Rt decreased and Iaw increased. Taking Raw,pleth as the gold standard, it is concluded that coherent estimation of parameters of DuBois model may be obtained from combined Zrs,tr and TGV measurements in normal subjects and moderately obstructed adults, but not in children with significant airway obstruction. This seems to be due to the systematic under-estimation of Raw*.