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Biomedical subjects

A Harf

Publications and source records attributed to A Harf.

At least 19 recordsLinked to original sources

High impedance mechanical ventilator for small animals: use of programmable controller.

We built a simple high impedance ventilator, which generates a pattern of flow largely independent of respiratory mechanics, to mechanically ventilate anaesthetized small animals. The system includes a source of compressed gas with an electronic valve and a flow controller on the inspiratory side and a second valve on the expiratory side. The two valves are driven by a programmable controller. To assess the performance of this ventilator we measured the delivered tidal volume while the ventilator was connected to an external, gradually varying resistance. This resistance was progressively increased to simulate bronchoconstriction of the respiratory system. Comparison with a volume-controlled ventilator was made. The use of a programmable controller also allows control of different patterns of mechanical ventilation, such as end-inspiratory pause or the static pressure-volume relationship, which can be used to perform lung function tests. The system is a simple, versatile device allowing both reliable mechanical ventilation and lung function assessment in small rodents and is suitable for routine use in laboratories.

Animals

A knowledge-based system for assisted ventilation of patients in intensive care units.

The procedure for weaning a patient with respiratory insufficiency from mechanical ventilation may be complex and requires expertise obtained by long clinical practice. We designed a knowledge-based system for the management of patients receiving respiratory support and implemented a weaning procedure. The system is intended for patients whose spontaneous respiratory activity is assisted by a Hamilton Veolar ventilator delivering a positive pressure plateau during inspiration (Pressure Support Ventilation mode). Our closed-loop real-time system running on a Personal Computer continuously adapts the assistance provided by the ventilator to the patient's evolution, and indicates when the patient can be withdrawn from the ventilator. Three parameters are used to appreciate the 'respiratory comfort' of the patient: breathing frequency, which we consider the most informative index, tidal volume and end-tidal CO2 pressure. A preliminary study of 19 patients was performed to evaluate the ability of our system to adapt the assistance to the patient's needs, with the main objective of facilitating weaning by gradually lowering the level of assistance. In 10 of these patients, considered as good candidates for weaning on the strength of objective criteria, the system maintained the breathing pattern in a zone of comfort for 95% of the period of assisted ventilation and stated that they were 'weanable'. This was consistent with the clinical evolution of all 10 patients. These results show that such a system can provide effective management for mechanically ventilated patients.

Adult

Test of 20 similar intensive care ventilators in daily use conditions--evaluation of accuracy and performances.

Infrequent control, aging of components, may compromise the accuracy of ICU ventilators. In order to assess the reliability of ventilators during their clinical use, we bench tested a group of 20 CPU1 ventilators (Ohmeda) sampled at random in several ICU units. We found major leaks in 5 ventilators, attributable to the disposable tubings used in these systems. Mean error in expired tidal volume and corresponding standard deviation (precision) were greater than 100 ml in two. Positive end expiratory pressure measurement comprised a mean error higher than 2 cm H2O in 40% of the ventilators tested. The valve opening pressure threshold was correlated to the inspiratory flow (r = 0.81) contrary to the valve opening delay (average 138 +/- 40 ms). These two parameters did not correlate with the age of the ventilator. Our study addresses the need for periodic control of ventilator performance in order to minimize the risks of errors and malfunctions.

Age Factors

Respiratory response to positive and negative inspiratory pressure in humans.

To investigate the effect of positive or negative inspiratory pressure on respiration, eight subjects breathed, either without or with added external dead space (VD, 600 ml), through either added inspiratory laminar flow resistances (RES; peak inspiratory airway pressure, Pinsp, down to -9 cmH2O) or with inspiratory pressure support (IPS; Pinsp up to +10 cmH2O). IPS, triggered by the subject's inspiratory effort, provided positive airway pressure throughout inspiration, but allowed for attainment of the subject's own respiratory pattern. The following main results were obtained with IPS or RES relative to the control (no IPS, no RES): (1) with VD, IPS led to small, but significant, increases in tidal volume (VT), respiratory frequency (fR) and ventilation (VE), with no changes in inspiratory time (TI) or duty cycle (TI/TT). Mean inspiratory flow (VT/TI) increased, and mouth occlusion pressure 0.1 sec after onset of inspiration (P0.1) decreased significantly with IPS. The changes during RES were essentially in the opposite direction; (2) without VD, similar, but smaller effects were observed, and only the changes in VT/TI and P0.1 during IPS were significant; (3) highly significant decreases were observed during IPS in end-tidal PCO2 (PETCO2); on the average from 39.6 to 29.2 Torr without VD, and from 45.7 to 39.3 Torr with VD breathing. A small, but significant decrease in PETCO2 occurred also during RES with VD. We conclude that while resistive loading is nearly completely compensated with but small changes in PETCO2, inspiratory pressure support leads to marked hyperventilation, which is not effectively counteracted by central timing commands.

Adult

Airway anesthesia during positive and negative inspiratory pressure breathing in man.

We have measured the effects of airway anesthesia (aerosolized 5% lidocaine) on the respiratory pattern during positive or negative inspiratory pressure in 8 resting subjects. The subjects breathed through a 600 ml dead space (peak inspiratory airway pressure, Paw = -2 cmH2O) without or with negative (approx. -5 or -10 cmH2O) or positive (approx. +5 or +10 cmH2O) inspiratory pressure, provided by a laminar flow resistance or a positive pressure source, respectively. Control measurements were performed before and after measurements with airway anesthesia. Measurements included tidal volume, respiratory frequency, ventilation, inspiratory and expiratory duration, occlusion pressure (P0.1) and end-tidal PCO2. None of the parameters measured was significantly altered by airway anesthesia, which was effective in suppressing the cough reflex. We conclude that information from lung afferents that are suppressed with the elimination of the cough reflex is not important for the breathing pattern during resting ventilation with elevated tidal volume (dead space load) and with positive or negative inspiratory pressure.

Adult

Risk factors for oxygen desaturation during sleep, after abdominal surgery.

The postoperative period after major abdominal surgery is known to be a period of increased episodic oxygen desaturation. In order to assess the risk factors for episodic desaturation, we have studied 29 surgical patients using pulse oximetry during the preoperative night (Npre) when they received benzodiazepine premedication and breathed air, and also during the first three nights after operation when they received nasal oxygen supplementation. Modal oxygen saturation (SpO2) exceeded 95% during all nights studied. The time spent at less than 90% (t90) and 85% (t85) SpO2 and the average SpO2 nadir (SpO2, nadir) did not differ each night. Heart rate was greater (mean 90.1 (SD 16.6) vs 68.2 (12.0) beat min-1, P < 0.001) during the second night after operation (N2) than during Npre. Before operation, the number of desaturations, t90 and t85 correlated with pharyngeal hypertrophy (P = 0.003, P = 0.002, P = 0.001, respectively). At the same time, t90 and t85 correlated with body mass index (P = 0.02 and P = 0.05, respectively). During N2, t90 correlated with radiological lung consolidation (P = 0.05) and SpO2, nadir correlated with FEV1 (P = 0.03). We conclude that there are several mechanisms responsible for oxygen desaturation and that these mechanisms differ before and after surgery.

Abdomen

Effects of neuraminidase on airway reactivity in the guinea pig.

We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae neuraminidase was administered intratracheally in guinea pigs, and airway reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated by histologic studies. Airway responsiveness was determined in anesthetized, tracheotomized, and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory system conductance was measured by the occlusion method. Neuraminidase injected intratracheally did not change airway reactivity to 10(-4) to 10(-2) M acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent aerosolized albuterol from inhibiting histamine-induced bronchoconstriction. Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M) before the concentration curve to aerosolized substance P was recorded, neuraminidase significantly reduced substance P-induced bronchoconstriction. When bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to 10(-2) M), which is devoid of positive charges, it did not differ significantly in guinea pigs pretreated with saline and those pretreated with neuraminidase. These results indicate that in the guinea pig, neuraminidase injected intratracheally does not induce non-specific airway hyperreactivity and may alter the binding of substance P to its receptors.

Albuterol

Use of the Blasius resistance formula to estimate the effective diameter of endotracheal tubes.

To early detect mucus deposition in endotracheal tubes (ETT), we propose using a geometric, flow-independent parameter, i.e., diameter of the ETT, based on a precise knowledge of ETT flow regime, instead of using the classic flow-dependent ETT resistance based on the empirical, nonlinear Rohrer equation. From the estimated slope of -0.24 derived from Moody diagrams characterizing the pressure-flow relationship in ETT of various inner diameters (D), we first assessed that the Blasius resistance formula slope of -0.25 could be applied to adult-size ETT, meaning that flow remains fully developed, turbulent, and hydraulically smooth (0.5 L/s less than or equal to V less than or equal to 1.4 L/s). Insertion into the ETT of a pressure catheter (external diameter: d) to stimulate in vivo measurements did not modify these results, provided the hydraulic diameter, D* = D - d, was substituted for D in the Blasius formula. The Blasius formula was then used to determine, from in vitro pressure and flow measurements in ETT before intubation and in ETT lined with dry mucus secretions, the effective diameter, shown here to be highly correlated to the actual diameter measured by volumetric water displacement. The effective ETT diameter was measured in eight patients at different stages after oral or nasal intubation. Compared with the actual ETT diameter measured before insertion, the effective diameter was slightly reduced (2.6 +/- 2.5%) during the first week of intubation and was strongly reduced (12.2 +/- 2.8%) during the second week.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Can portable chest x-ray examination accurately diagnose lung consolidation after major abdominal surgery? A comparison with computed tomography scan.

PURPOSE: To prospectively quantify the degree of accuracy of portable chest x-ray film examination in the detection of postoperative lung consolidations. STUDY: Nineteen patients had a chest x-ray film and computed tomography (CT) scan the day before and 48 h following elective abdominal aortic replacement. RESULTS: The diagnosis of lung consolidations by x-ray film examination showed sensitivity of between 0.33 and 1.00, depending on the lung zone considered (lower at the lung bases). Specificity always was greater than 0.79. Radiologic lung volume decreased 16 percent postoperatively (p < 0.01) on average and noninflated parenchyma increased by a factor of 3 (p < 0.0001). Postoperatively, PaO2 correlated with the amount of condensed lung by CT scan (p < 0.002). CONCLUSION: In postoperative conditions, x-ray film examination is a method which presents good specificity but poor sensitivity in the diagnosis of lung consolidations.

Abdomen

Influence of posture on mechanical parameters derived from respiratory impedance.

The influence of posture on respiratory mechanics was investigated in 10 healthy volunteers, using the forced pseudorandom noise technique. Subjects were studied in four randomly selected positions: sitting; sitting with the head turned sideways; supine; and prone with the head turned sideways. Respiratory compliance (Crs), inertance (Irs) and resistance estimated at 4 Hz (R4), were calculated by fitting respiratory impedance by a 4 parameter model with a frequency dependent resistance. When subjects changed from sitting to lying, whilst maintaining the head in the same position in relation to the body, Irs increased and Crs decreased, probably due to gravitational effects. R4 was significantly higher in the supine position than in either of the sitting or the prone positions. These results demonstrate that changes in lung volume cannot completely explain the influence of posture on respiratory resistance, and indicate upper airway geometry as a determinant factor of respiratory resistance.

Adolescent

Effects of platelet-activating factor on lung epithelial permeability in the guinea-pig.

We examined the effects of platelet-activating factor (PAF) on lung epithelial permeability by measuring the clearance of intratracheally administered 99m-technetium-labeled diethylene triamine penta-acetic acid (99mTc-DTPA) in guinea-pigs which were anaesthetised, paralysed and mechanically ventilated. The clearance of the radiolabeled tracer molecule 99mTc-DTPA from airways to the blood was expressed as changes in counts/min corrected for background. For each guinea-pig, 99mTc-DTPA clearance was assessed before and after i.v. PAF administration, when tracheal pressure had returned to near control values. Doses of 10, 50 and 100 ng/kg of PAF caused dose-dependent increases in 99mTc-DTPA clearance of 7 +/- 3%, 38 +/- 7% and 65 +/- 11% respectively. The respective effects of 0.5 mg/kg of the beta 2-adrenergic agonist salbutamol and 0.3 mg/kg of the alpha 1-adrenergic agonist methoxamine on the increase in lung epithelial permeability induced by 50 ng/kg PAF were also studied. Salbutamol significantly reduced the acute bronchoconstrictor effects of PAF, but did not affect the increase in lung epithelial permeability, which was 58 +/- 10%. Conversely, methoxamine significantly enhanced the bronchoconstrictor effects of PAF but inhibited the lung epithelial permeability increase, which was only 10 +/- 13%. In the absence of PAF, salbutamol significantly increased this permeability by 49 +/- 11%, whereas methoxamine alone slightly reduced, it by -11 +/- 4%. These results demonstrate that PAF increases lung epithelial permeability and suggest that vascular surface area recruitment may explain this increase.

Albuterol

Pressure support ventilation using a new tracheal gas injection tube.

In order to explore new types of jet ventilation, we tested a tracheal gas injection tube (TGIT) which included six thin capillaries and provided high pressure injection. The driving pressure was chosen to yield a plateau of inspiratory tracheal pressure of 10 cm H2O. An original controller was built to monitor spirometry and trigger injection in order to deliver both pressure controlled ventilation (PCVTGIT) and a new mode of inspiratory pressure support jet ventilation (IPSTGIT). The PVCTGIT mode maintained the same end-tidal carbon dioxide concentration as conventional ventilation with the same tidal and minute ventilation. We studied 10 patients after abdominal surgery. During spontaneous breathing, the patients were allowed to breathe through the tube, successively with and without IPSTGIT. IPSTGIT, compared with spontaneous breathing increased minute ventilation (from 5.7 (SD 1.6) to 7.1 (1.7) litre min-1) (P less than 0.001). It reduced the total work of breathing (from 0.625 (0.223) to 0.263 (0.151) J litre-1, respectively) (P less than 0.01) and the occlusion pressure (from 2.62 (1.28) to 1.36 (0.74) cm H2O, respectively) (P less than 0.01). It is concluded that this TGIT used with a specific system for sensing and triggering ventilation allows inspiratory pressure support during low frequency jet ventilation.

Female

Changes in the distribution of ventilation and perfusion associated with separation from mechanical ventilation in patients with obstructive pulmonary disease.

A trial of separation from mechanical ventilation may induce an abnormal respiratory pattern and a maldistribution of ventilation-to-perfusion ratios (VA/Q), especially in patients with chronic obstructive pulmonary disease. This study was designed to assess the effects of three different modes of ventilation on the distribution of global and also regional VA/Q in eight patients with chronic obstructive pulmonary disease recovering from acute respiratory failure who remained dependent on mechanical ventilation after more than 5 days of attempted separation from the ventilator. VA/Q distribution was assessed using the multiple inert gas and isotopic scanning methods after 30 min each of controlled mechanical ventilation (CMV), 10 cmH2O inspiratory pressure support, and spontaneous breathing (SB). Controlled ventilation was provided at a respiratory rate ranging from 12 to 18 breaths per min and a tidal volume of 8 ml.kg-1. In comparison to CMV, SB resulted in a decrease in tidal volume (from 512 +/- 144 to 301 +/- 102 ml, P less than 0.01), and an increase in respiratory rate (from 15.5 +/- 3.2 to 27.3 +/- 15.0 breaths per min, P less than 0.05), which increased dead space (+7.1% of minute ventilation), cardiac output (+36%), and the perfusion to areas of low VA/Q (+8.9% of cardiac output) (P less than 0.05, P less than 0.001, and P less than 0.05, respectively). Isotopic scans revealed a horizontal craniocaudal difference of VA/Q in all modes, with the lowest VA/Q zones at the basal part of the lungs (mean basal VA/Q 0.58 in SB and 1.05 in CMV).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Inspiratory pressure support compensates for the additional work of breathing caused by the endotracheal tube.

Breathing through an endotracheal tube and a demand valve may increase the work performed by the respiratory muscles. Inspiratory pressure support (PS) is known to reduce this work and might therefore compensate for this increased requirement. To test this hypothesis, we measured the work of breathing (WOB) in 11 patients whose tracheas were intubated. Five had no intrinsic lung disease, but six had chronic obstructive lung disease. We compared WOB measurements taken under several sets of conditions: during assisted breathing at four levels of PS, during unassisted breathing and connection to a T-piece, and after extubation of the trachea. During unassisted breathing via the ventilator circuit (PS set at 0 cmH20), the WOB per minute was greater than that after extubation, with a mean increase (+/- standard deviation) of 68 +/- 38% (10.3 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.01). While breathing through the T-piece, the WOB was 27 +/- 18% greater than after tracheal extubation (8.2 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.05). The principal reason why inspiratory work decreased after extubation was that the ventilatory requirement decreased. For each patient, we determined retrospectively, after extubation, the level of PS that had reduced WOB to its postextubation value and obtained levels ranging from 3.4 to 14.4 cmH2O. The PS level at which additional WOB was compensated for, was greater in patients with chronic lung disease than in those free of lung disease (12.0 +/- 1.9 vs. 5.7 +/- 1.5 cm H2O, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

5-Hydroxytryptamine-induced bronchoconstriction in the guinea-pig: effect of 5-HT2 receptor activation on acetylcholine release.

1. The bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were studied in the guinea-pig to establish whether they are partly attributable to parasympathetic activation within the airways. 5-HT dose-response curves were constructed in anaesthetized and ventilated guinea-pigs pretreated with saline, or by bilateral cervical vagotomy or vagotomy plus atropine 3 mg kg-1, i.v. Vagotomy had no effect on 5-HT-induced bronchoconstriction but vagotomy plus atropine significantly reduced it. 2. To determine whether parasympathetic activation within the airways resulted from pre- or postganglionic stimulation, 5-HT dose-response curves were constructed for two groups of vagotomized guinea-pigs treated with hexamethonium 2 mg kg-1, or hexamethonium 2 mg kg-1, plus atropine 3 mg kg-1. Guinea-pigs treated with hexamethonium plus atropine experienced significantly less 5-HT-induced bronchoconstriction than those treated with hexamethonium alone. 3. To characterize the subtype of 5-HT receptors involved in the activation of the parasympathetic system by 5-HT, dose-response curves to 5-HT were constructed for four groups of vagotomized guinea-pigs treated with saline, 1 mg kg-1 of the 5-HT3 antagonist ICS 205-930, or either 0.01 or 0.1 mg kg-1 of the 5-HT2 antagonist ketanserin. ICS 205-930 enhanced 5-HT-induced bronchoconstriction but 0.01 mg kg-1 ketanserin inhibited it significantly and 0.1 mg kg-1 ketanserin abolished it. To confirm the involvement of 5-HT2 receptors in these responses, we studied the effects in vagotomized guinea-pigs of atropine on the bronchoconstriction induced by the 5-HT2 agonist,x alpha-methyl-5-HT, infused at rates of 40 and 80ngkg-1s-'. At both rates, atropine significantly reduced the bronchoconstrictor responses to alpha-methyl-5-HT. 4. The above results indicate that 5-HT-induced bronchoconstriction is indeed partly mediated by parasympathetic activation within the airways. This activation is mediated by stimulation of 5-HT2 receptors which are probably located on the postganglionic parasympathetic nerve endings.

Acetylcholine

Shunt effect of gas compression inside pneumotachographs during forced oscillations.

Determination of the frequency response of pneumotachographs is needed whenever they are used to measure high-frequency flows, such as in the forced oscillation method. When screen and capillary pneumotachographs are calibrated using an adiabatic compression in a closed box as a reference impedance, they can be adequately described by a series of inertial-resistive elements. However, this type of reference impedance strongly differs from the actual respiratory impedance (ZL). We studied the frequency response of pneumotachographs up to 250 Hz in reference to the impedance of a compressible gas oscillating in a long tube, taken as a more generalizable model of actual ZL. We found that, with this device, the series resistance-inertance models fail to describe the frequency response of the pneumotachograph. However, when compressible effects in the pneumotachograph are taken into account by adding to the resistive models a compliance (Cpn) corresponding to the compression in half of the inner volume of the pneumotachograph, the agreement with experiments becomes satisfactory. Gas compression-related phenomena were demonstrated to be negligible only when the parameter omega Cpn magnitude of ZL is much smaller than 1 (omega pulsation). Results obtained in normal humans have shown that such a correction is required above 100 Hz. Similar correction at lower frequency might also be necessary in cases of large respiratory impedance (e.g., babies, subjects with pathological lungs, and intubated subjects).

Humans

Effects of substance P and calcitonin gene-related peptide on the pulmonary circulation.

To assess the in vivo effects of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) on the pulmonary vascular bed, the hemodynamic responses to both CGRP and SP were examined in the in situ-perfused lung lobe of open-chest anesthetized pigs. Peptides were infused into the lobar artery under conditions of elevated pulmonary vascular tone by prostaglandin F2 alpha (PGF2 alpha, 20 micrograms/min). Pulmonary airway lobar dynamic compliance (Cdyn) and airway resistance (Re) were computed from simultaneously measured airway pressure and airflow entering the lobe through a Carlens endobronchial divider. PGF2 alpha infusion slightly reduced Cdyn (-20%) and increased Re (+11%) while lobar arterial pressure rose from 14 +/- 1 to 31 +/- 2 mmHg (n = 12). In these conditions, lobar artery infusion of SP (0.5-50 pmol/min) or CGRP (15-5,000 pmol/min) produced a dose-dependent decrease in the pressor response to PGF2 alpha, reaching -54 +/- 3 and -64 +/- 7%, respectively, without alterations in lung mechanics. On a molar basis, SP was more effective than CGRP; its vasodilatory effect was more rapid and of shorter duration. Higher CGRP infusion rates were not studied because of marked systemic hypotension. SP infused at 150, 500, and 1,000 pmol/min significantly reduced Cdyn by 12 +/- 2, 24 +/- 4, and 62 +/- 7%, respectively, but also induced a rise in lobar arterial pressure and a fall in systemic arterial pressure. The results show that both SP and CGRP are potent pulmonary vasodilators. In contrast to CGRP, which did not affect lung mechanics, high infusion rates of SP decreased Cdyn and increased Re.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance