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Biomedical subjects

B Lachmann

Publications and source records attributed to B Lachmann.

At least 91 records · Page 5Linked to original sources
PubMed1994

Evaluation of lung function changes before and after surfactant application during artificial ventilation in newborn rats with congenital diaphragmatic hernia.

Patients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research into optimal ventilatory regimen is essential to improve survival rate and to prevent ongoing lung damage. Against this background, the effect of exogenous surfactant application is evaluated. In newborn rats, CDH was induced after a single dose of 2,4 dichloro-4'-nitrophenyl (Nitrofen) (400 mg/kg) on day 10 of gestation. The newborn rats were intubated immediately after hysterotomy, transferred to a heated multichambered body plethysmograph, and artificially ventilated. Inspiratory peak pressures were initially set at 17 cm H2O, with positive end-expiratory pressure at 0 cm H2O and FIO2 at 1.0. The pressure was raised in steps of 5 cm H2O, from 5 to 30 cm H2O, to obtain pressure-volume diagrams at 0, 1, and 6 hours of artificial ventilation. These measurements were obtained in controls and in CDH rats with and without endotracheal installation of bovine surfactant (n = 4 to 10 in each group). Significant differences in lung volume between CDH and control rats were observed at all time-points. Surfactant application had a positive effect on lung volume, especially in control rats at t = 1 hour. No significant differences were observed between the CDH groups at t = 1 or t = 6 hours. In this animal model, the effect of artificial ventilation as well as the beneficial short-term effect of exogenous surfactant application have been evaluated. A continued positive effect on lung volume in CDH lungs could not be determined. Routine administration of exogenous surfactant in human CDH patients is not supported by these experimental results.

Animals↗
PubMed1994

Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS.

The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R) existed over either volume controlled ventilation (VCV) with measured best-PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure. Fifteen adult pigs were used for the study. Respiratory failure was induced by surfactant depletion by repeated lung lavage. The different therapeutic approaches were applied randomly to each pig for 1 h. Measurements of gas exchange, airway pressures and haemodynamics were performed during ventilatory and haemodynamic steady state. Paco2 was kept constant in all modes. At almost similar total-PEEP, Pao2 values were significantly higher with LFPPV-ECCO2R compared to VCV with best-PEEP. Peak inspiratory pressure (PIP) and intrapulmonary pressure amplitude defined as the difference between PIP and total-PEEP were significantly lower with PRVCV and LFPPV-ECCO2R compared to VCV with best-PEEP. There was no significant difference between the modes concerning cardiocirculatory parameters. PRVCV with I/E ratio of 4:1 and LFPPV-ECCO2R proved to be better modes to achieve better gas exchange and lower PIP at lower intrapulmonary pressure amplitudes. It is concluded that PRVCV is an adequate form of treatment under these experimental conditions imitating acute respiratory failure, without necessitating other invasive measures.

Acute Disease↗
PubMed1993

Surfactant treatment of respiratory failure induced by hydrochloric acid aspiration in rats.

BACKGROUND: The surfactant system seems to be involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration. This study was an investigation of the effect of different treatment strategies using an exogenous surfactant preparation on lung function of rats suffering from respiratory failure after intratracheal HCl instillation. METHODS: In rats anesthetized with halothane, nitrous oxide, and oxygen, tracheotomy was performed and the lungs were mechanically ventilated. Respiratory failure was induced by intratracheal instillation of HCl (0.1 N, 3 ml/kg). After the PaO2 decreased to < 200 mmHg, the animals were randomly divided into five groups. Group I received no treatment; group II received a natural surfactant preparation intratracheally (200 mg/kg); group III underwent bronchoalveolar lavage (BAL) with saline, followed by surfactant treatment (200 mg/kg); and groups IV and V underwent BAL with saline and a diluted surfactant suspension (3.3 mg/ml in 30 ml/kg), respectively. Groups IV and V received a second and third BAL 60 and 120 min after the first lavage. Blood gas analysis and protein measurements in BAL fluids were performed. RESULTS: Gas exchange improved in Groups III and V only. Protein concentrations were high in all BAL fluids. In the rats receiving BAL three times (groups IV and V), a decrease in protein concentration was observed. CONCLUSIONS: From these results, it was concluded that plasma-derived proteins (which are known to inhibit surfactant function) are washed out of the alveoli by BAL, resulting in improved efficacy of surfactant treatment.

Animals↗
PubMed1993

Intratracheal perfluorocarbon administration as an aid in the ventilatory management of respiratory distress syndrome.

BACKGROUND: Respiratory distress syndrome carries a high morbidity and mortality when treated with mechanical ventilation with positive end-expiratory pressure. Perfluorocarbon liquids are employed in liquid ventilation due to low surface tension and high gas solubility. To assess whether intratracheal administration of the perfluorocarbon, perflubron, in combination with conventional mechanical ventilation could be of therapeutic benefit in respiratory distress syndrome, the authors tested the effects of different doses of intratracheal perflubron administration on gas exchange and lung mechanics in adult animals with respiratory failure during a 6-h observation period. METHODS: Respiratory failure was induced in 30 rabbits by saline lung lavage (arterial oxygen tension < 100 mmHg at 100% oxygen with the following ventilator settings: tidal volume, 12 ml.kg-1; respiratory frequency, 30 per min; inspiratory/expiratory ratio, 1:2; and positive end-expiratory pressure of 6 cm H2O). Twenty-four rabbits were treated with different perfluorocarbon doses (3, 6, 9, and 12 ml.kg-1), and the remaining six served as controls while mechanical ventilation was continued with the aforementioned settings. Additionally, in ten healthy rabbits who were used as healthy controls, the lungs were mechanically ventilated either alone or in combination with intratracheal perfluorocarbon administration (3 ml.kg-1) for 6 h. RESULTS: In all treatment groups, arterial oxygen pressure increased significantly (P < 0.0001) in a dose-related fashion (193 +/- 40, 320 +/- 70, 353 +/- 125, and 410 +/- 45 mmHg at 15 min), and peak airway pressures decreased significantly (range, 18-23%; P < 0.0001) from pretreatment values. These findings were in contrast to those for the control group. The improvements were time-dependent in all four tested perfluorocarbon doses. However, the improvements in pulmonary parameters could be extended to 6 h only in groups treated with 9 ml.kg-1 and 12 ml.kg-1 perflubron. At the end of the 6-h period, the data for these two groups showed significantly higher arterial oxygen pressure (230 +/- 84 and 197 +/- 130 mmHg, respectively; P < 0.05) and lower inflation pressures than the pretreatment data for these groups and the data for the control group at 6 h. There were no clinically significant changes in pulmonary parameters in healthy animals due either to mechanical ventilation alone or mechanical ventilation in combination with intratracheal perfluorocarbon administration for 6 h. CONCLUSIONS: The results of this study imply that there is no association between the lung mechanics and gas exchange parameters for mechanical ventilation in combination with intratracheal perfluorocarbon administration. The data suggest that this type of perfluorocarbon administration with conventional mechanical ventilation offers a simple, alternative treatment of respiratory distress syndrome. With this technique, adequate pulmonary gas exchange can be maintained at relatively low airway pressures with high perfluorocarbon doses for several hours.

Animals↗
PubMed1993

Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone.

OBJECTIVE: To study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DESIGN: Prospective randomized, controlled study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Twelve adult New Zealand white rabbits. INTERVENTIONS: Respiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. MEASUREMENTS AND MAIN RESULTS: Before and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by-breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 +/- 7 torr [8.2 +/- 0.9 kPa] to 470 +/- 47 torr [62.6 +/- 6.2 kPa]) and in functional residual capacity (7.6 +/- 1.4 to 17.7 +/- 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. CONCLUSIONS: The findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance.

Animals↗
PubMed1993

Intratracheal perfluorocarbon administration combined with mechanical ventilation in experimental respiratory distress syndrome: dose-dependent improvement of gas exchange.

OBJECTIVES: To test the efficacy of intratracheal instillation of a perfluorocarbon, combined with conventional mechanical ventilation, as well as to establish the dose response of this application on pulmonary parameters in adult animals with acute respiratory failure. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Anesthesiology laboratory of a university. SUBJECTS: Twelve, adult male New Zealand rabbits. INTERVENTIONS: After inducing respiratory failure by repeated lung lavage with saline, one group of animals was treated with perfluorocarbon, while another group was treated with saline to serve as controls (n = 6 per group). Treatment consisted of intratracheal instillation of incremental doses of 3 mL/kg of each liquid up to a total volume of 15 mL/kg. Animals were mechanically ventilated for 15 mins after each treatment dose with volume-controlled ventilation, a tidal volume of 12 mL/kg, frequency of 30 breaths/min, FIO2 of 1.0, and a positive end-expiratory pressure of 6 cm H2O. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and lung mechanics were determined. In the perfluorocarbon group, PaO2 increased with increases in dosage from 75 +/- 15 to 420 +/- 27 torr (10.0 +/- 2.0 to 55.9 +/- 3.6 kPa); PaCO2 decreased from 49 +/- 6 to 43 +/- 5 torr (6.5 +/- 0.8 to 5.7 +/- 0.6 kPa) after the first dose, and remained stable thereafter. Airway pressures were significantly lower after treatment compared with pretreatment values. CONCLUSION: The remarkable improvements in pulmonary parameters suggest that this type of ventilatory support offers an effective and simple method of perfluorocarbon application in acute respiratory failure.

Acute Disease↗
PubMed1993

On the preservation and regulation of vascular tone in arteriovenous anastomoses during anesthesia.

In conscious pigs, arteriovenous anastomoses (AVAs) are in a constricted state so that < 5% of intra-atrially injected radioactive (15-microns-diam) microspheres are shunted to the lungs. Many of the anesthetic regimens frequently used in cardiovascular research dilate AVAs, thereby greatly increasing the percentage of microspheres reaching the lungs. This may seriously limit extrapolation of results obtained under anesthesia to the conscious state. We now describe that anesthesia with a combination of fentanyl and thiopental preserves the tone of AVAs, maintaining shunting under 4% of cardiac output. Furthermore, we studied in the carotid circulation of this model whether norepinephrine or 5-hydroxy-tryptamine (5-HT), both contained in perivascular nerves, is responsible for this tone. Consecutive antagonism of alpha 1-, alpha 2-, 5-HT1, and 5-HT2 receptors was obtained by sequential injection of prazosin, phentolamine, ketanserin, and methiothepin. Prazosin increased AVA blood flow, partly at the expense of extracerebral tissue blood flow, but preserved cerebral blood flow. None of the other antagonists had any additional significant effect. Therefore, in this model the tone in AVAs seems to be maintained by sympathetic norepinephrine-containing nerves via alpha 1-adrenoceptors.

Anesthesia↗
PubMed1993

Comparison of ventilatory support with intratracheal perfluorocarbon administration and conventional mechanical ventilation in animals with acute respiratory failure.

We investigated the efficacy of intratracheal perfluorocarbon (PFC) administration combined with mechanical ventilation to support gas exchange in adult animals with acute respiratory failure. These were compared with a similar group of animals treated with continuous positive-pressure ventilation (CPPV) with respect to respiratory parameters and postmortem lung histology. After lung lavage with saline, 18 adult rabbits were divided into three groups (n = 6 per group). All groups received conventional CPPV. Additionally, one group received intratracheal PFC administration at a volume of 18 ml/kg (corresponding to functional residual capacity) (PFC group); another received 18 ml/kg of saline administration (saline group), and the last had no further treatment (CPPV group). All groups were ventilated for 3 h using 100% oxygen, with the same ventilator settings of tidal volume of 12 ml/kg, respiratory frequency of 30/min, and positive end-expiratory pressure of 6 cm H2O. In the PFC group, PaO2 increased from 67.2 +/- 11.4 to 424.2 +/- 14 mm Hg and remained stable for 3 h with well-preserved PaCO2 values. Only in the PFC group were significant decreases in airway pressures and increase in respiratory system compliance seen. In the CPPV group, PaO2 stayed around 60 mm Hg and PaCO2 gradually increased. PFC treatment with conventional mechanical ventilation in acute respiratory failure proved to be a successful supportive technique to improve gas exchange at low inflation pressures.

Acute Disease↗
PubMed1993

Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged rabbits are influenced by the instillation technique.

Surfactant bolus instillation has been reported to cause changes in arterial blood pressure (BP) and cerebral blood flow velocities which may increase the risk of intraventricular haemorrhage. To avoid these effects, slow tracheal infusion was evaluated as a possible alternative method of surfactant administration. Saline lung lavages were performed in 13 anesthetized and artificially ventilated adult rabbits to produce respiratory distress syndrome. Curosurf (CS, 200 mg/kg) labeled with 14C-dipalmitoyl-phosphatidylcholine (-DPPC) and/or red microspheres (RMS) was instilled into the trachea either as a single bolus (n = 8) or by infusion during 45 min via a side-channel within the wall of the tracheal tube (n = 5). An arterial cannula was placed for monitoring of blood gases and BP. To determine surfactant distribution, the lungs were cut into 60-70 pieces and radioactivity and/or the number of RMS were measured in each piece. The distribution of RMS was closely related to the distribution of 14C-DPPC (r = 0.96). Bolus instillation of CS led to a prompt and sustained increase in PaO2 (from < 10.5 to > 40 kPa within 2 min), a transient decrease in BP, and a reasonably homogeneous pulmonary surfactant distribution. Tracheal infusion of CS changed neither BP nor PaO2 during the observation period of 60 min. The pulmonary distribution of CS was extremely uneven after infusion. The distribution of exogenous surfactant and its effects on gas exchange are influenced by the instillation method. An inadequate instillation technique may add to the causes of "poor response" after surfactant replacement.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Prevention of respiratory failure after hydrochloric acid aspiration by intratracheal surfactant instillation in rats.

Because the surfactant system probably is involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration, we investigated the effects of different ventilation strategies and intratracheal surfactant instillation at different time intervals on the course of pulmonary gas exchange after HCl aspiration in rats. In this study rats were anesthetized and mechanically ventilated via a tracheostomy. Respiratory failure was induced by intratracheal instillation of 3 mL/kg 0.1 N HCl. Animals (n = 49) were divided into nine groups: Groups 1 and 2 through 9 were ventilated with peak airway pressure/positive end-expiratory pressure of 14/2 and 26/6 cm H2O, respectively; Groups 3 and 4 received surfactant (200 mg/kg) intratracheally, 1 and 10 min after HCl aspiration; Groups 5 and 6 received saline, 1 and 10 min after HCl aspiration; Groups 7 and 8 received surfactant, 60 and 90 min after HCl aspiration; Group 9 received saline instead of HCl. Gas exchange deteriorated in Groups 1, 2, 5, 6, 7, and 8, whereas respiratory failure could be prevented in Groups 3 and 4. After deterioration of gas exchange, surfactant treatment prevented further decrease of PaO2 values in Group 7, whereas no effect on gas exchange was observed in Group 8; intratracheal instillation of saline had no effect on gas exchange (Group 9). These results suggest that surfactant should be given as early as possible after aspiration of gastric contents to prevent development of respiratory failure.

Animals↗
PubMed1992

Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia.

The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated. In these animals which developed PCP with severe respiratory failure after s.c. administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2. Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated. These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations.

Animals↗
PubMed1992

Acute respiratory failure during pneumonia induced by Sendai virus.

In this study a model of acute respiratory failure due to viral pneumonia in rats, closely resembling ARDS, is presented. Severe respiratory failure with lethal outcome in four days was induced by infection concentrated Sendai virus aerosol. This model permits evaluation of different therapeutical approaches for improving gas exchange during ARDS. Furthermore, preliminary results of surfactant substitution therapy in this model are presented.

Animals↗