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Biomedical subjects

R Rossaint

Publications and source records attributed to R Rossaint.

At least 109 records · Page 6Linked to original sources
PubMed2000

Comparative analysis of metabolism of medium- and plasma perfused primary pig hepatocytes cultured around a 3-D membrane network.

Culture media are frequently used in the evaluation of metabolical functions of hepatocytes in hybrid liver support systems (hLSS). However, media compositions differ substantially from those of plasma. Therefore, our study was designed to investigate whether current in vitro studies with medium are suitable to assess the metabolical competence of hLSS-cultures during clinical application as well as to explore whether the cell nutrition with medium provides a suitable modus operandi for stand by cultivation. Paired bioreactor cultures were perfused with either Williams' Medium E (MPB) or human plasma (PPB). About 6x108 primary pig hepatocytes (>97% viability) were cultured in three laboratory scale bioreactors designed according to Gerlach's bioreactor-concept. Different perfusion protocols were initiated after a standardised period allowing for cell attachment and reorganisation in aggregates. Whereas patterns of enzyme release were similar in both protocols the metabolical behaviour was different between MPB (anabolic state) and PPB (catabolic state). Furthermore, compared to MPB the lidocaine-MEGX-tests for PPB demonstrated lower MEGX-concentrations and a different reaction pattern. We conclude that the nutrition of hepatocytes with medium during the stand by period itself might influence the cell function and subsequently the efficacy of the hLSS-treatment during clinical application.

Animals↗
PubMed2000

Development of a special catheterbag to enable artificial organ evaluation in conscious, unrestrained pigs: technical note.

Pigs are widely used as models for a variety of human diseases, because many of their physiological functions closely resemble those of humans. However, information on instrumentation techniques is still scarce. In particular, experiments in conscious pigs focused on extracorporeal circuits are connected to a variety of methodical problems with respect to the handling of the animals. Usually, pigs are placed in restraint-slings during the application of an extracorporeal system. However, this method of restraint may lead to excessive mental distress even in trained animals. The latter might influence the results and certainly affects principles of animal welfare. Our own experiences with instrumented, conscious, but unrestrained dogs encouraged us to modify methods used for the fixation of in-dwelling central venous catheters in dogs with special regard to the species specific behaviour and phenotype of pigs. A cord retractable leash (CRL) was used for maintaining a safe distance between the animal and the outer ends of the catheters. To prevent dehiscences of the required fixation sutures a new catheter bag (CB) was designed to counteract tension forces caused by the CRL's spring-mechanism. The combination of both the CRL and CB enabled us to conduct safe experiments with conscious, unrestrained pigs. We alleviated the mental distress these animals were exposed to in comparison to former methods based on restraint of the animals.

Animals↗
PubMed1999

Inhaled prostacyclin in the treatment of pulmonary hypertension.

UNLABELLED: Pulmonary hypertension can occur primarily with an unknown aetiology or secondary in association with cardiac or pulmonary disorders such as congenital diaphragmatic hernia, idiopathic respiratory distress syndrome, acute respiratory distress syndrome (ARDS), congenital heart disease with malformation of the pulmonary blood vessels, chronic obstructive lung disease and following cardiac surgery. Prostacyclin (PGI(2)), an arachidonic acid metabolite, has been evaluated for its efficacy in the treatment of pulmonary hypertension and for its use in assessing the reversibility of the disorder prior to surgical interventions. While the intravenous application of PGI(2) can cause a decrease not only of the pulmonary but also of the systemic vascular tone, aerosolised PGI(2) results in a selective pulmonary vasodilation without affecting the systemic blood pressure. Furthermore, aerosolised PGI(2) can improve gas exchange and pulmonary shunt in clinical settings of impaired ventilation/perfusion ratio such as ARDS, due to the redistribution of pulmonary blood flow from nonventilated to ventilated, aerosol-accessible lung regions. CONCLUSION: Aerosolised prostacyclin can be a valuable tool in the treatment and diagnostic evaluation of elevated pulmonary vascular resistance and impaired pulmonary gas exchange. Reservations must be made for its long-term use, as its short half-life necessitates continuous inhalation.

Administration, Inhalation↗
PubMed1999

[Extracorporeal liver assist devices in acute liver failure].

The acute liver failure (ALF) is a complex syndrome resulting from loss of synthetic and metabolic functions of the liver. Despite recent advances in intensive care medicine patients with severe ALF have a very high mortality and the orthotopic liver transplantation still remains the only proven effective treatment of ALF. Numerous attempts have been made to improve survival by using various extracorporeal support techniques, but none of these therapeutic approaches was able to increase the survival rate. Liver support systems based on detoxification procedures only could not influence the deleterious course of the disease. It is certain that an ideal liver support system should be capable to fulfil the liver's essential synthetic and metabolic functions as well as detoxification and excretion. Over the last years the development of hybrid liver assist devices has aimed at replacing these liver functions and therefore might give an advantage over earlier systems based on detoxification techniques only. This article gives a short review of the various liver support systems and focuses then on the hybrid liver support systems, their construction and the remaining problems after the first clinical applications.

Critical Care↗
PubMed1999

[Respiratory pattern and respiratory strain in automatic tube compensation and inspiratory pressure support].

STUDY OBJECTIVE: To investigate whether automatic tube compensation (ATC) or conventional pressure support (PS) is suitable to compensate for the work of breathing imposed by the breathing circuit without altering the breathing pattern. METHODS: Breathing pattern and work of breathing were measured in healthy volunteers. After a 20 min period of quiet breathing through a mouth piece (control) the volunteers were breathing through a 8.0 mm ID endotracheal tube (ETT) with four different settings: CPAP at 0 mbar, ATC, PS 5 mbar, PS 10 mbar. Each mode was applied for a 20 min period. At the end of each period data from 10 consecutive breaths were analyzed and averaged. Tidal volume (VT), breathing frequency (f), and minute ventilation (Ve) were determined from the stored gas flow tracings. Work of breathing was assessed as the pressure time product (PTP) calculated from the transdiaphragmatic pressure (Pdi) using a combined esophageal and gastric balloon catheter. RESULTS: During the control period the breathing pattern was as follows: VT = 882 +/- 277 ml, f = 13.7 +/- 5/min, Ve = 11.5 +/- 4.2 L/min. Maximal Pdi was 9.2 +/- 5.4 mbar and PTP was 11.3 +/- 7.1 mbar x s. Breathing CPAP through the ETT resulted in a slight increase in Pdi (10.8 +/- 5.4 mbar) and PTP (14.8 +/- 10.4 mbar x s) with an unchanged breathing pattern. However, for the same amount of unloading from respiratory workload ATC did not alter the breathing pattern, whereas PS 5 mbar and PS 10 mbar resulted in a clear increase in VT (1014 +/- 202 ml, 1336 +/- 305 ml, respectively). CONCLUSION: From the presented data in healthy volunteers it might be concluded that ATC and PS 5 mbar and 10 mbar are suitable modes for unloading the respiratory system from work imposed by the breathing circuit. ATC does not alter the breathing pattern in contrast to PS which results in an increased tidal volume. Therefore, the exact compensation of the work imposed by the ETT during ATC seems to be advantageous over ATC to assess the actual breathing pattern.

Adult↗
PubMed1999

Combination of inhaled nitric oxide and intravenous prostacyclin for successful treatment of severe pulmonary hypertension in a patient with acute respiratory distress syndrome.

OBJECTIVE: To investigate the combination of inhaled nitric oxide (iNO) and intravenously administered prostacyclin (i.v. PGI2) in a patient with severe pulmonary hypertension and acute respiratory distress syndrome (ARDS). DESIGN: Single case study. SETTING: Intensive care unit of a university hospital. METHODS: In an ARDS patient with severe pulmonary hypertension, gas exchange and hemodynamics were measured during combined treatment with iNO and i.v. PGI2. On two subsequent days, a protocol consisting of four 20-min periods was performed: baseline, 10 ppm iNO, 10 ppm iNO plus 4 ng kg-1 min-1, and 4 ng kg-1 min-1 PGI2 alone. At the end of each period hemodynamic and gas exchange data were obtained. RESULTS: The combination of iNO and i.v. PGI2 resulted in a marked decrease in pulmonary artery pressure and a concomitant increase in cardiac output which was more pronounced than the effect of either drug alone. During iNO, as well as during the combination of iNO and i.v. PGI2, oxygenation was improved, whereas during i.v. PGI2 alone oxygenation was worse than baseline. CONCLUSION: We conclude that the combination of iNO and i.v. PGI2 might be more useful than either drug alone when severe pulmonary hypertension leading to impaired right ventricular function is present in ARDS. A systematic study of this observation is warranted.

Administration, Inhalation↗
PubMed1999

Effect of aerosolized prostacyclin and inhaled nitric oxide on experimental hypoxic pulmonary hypertension.

OBJECTIVE: To compare the effect of different concentrations of inhaled nitric oxide and doses of nebulized prostacyclin on hypoxia-induced pulmonary hypertension in pigs. DESIGN: Prospective, controlled animal study. SETTING: Animal research facilities of an university hospital. INTERVENTIONS: After reducing the fraction of inspired oxygen (FIO(2)) from 1.0 to 0.1, two groups of five pigs each were submitted to inhalation of three concentrations of nitric oxide (5, 10 and 20 ppm) or three doses of prostacyclin (2.5, 5, 10 ng x kg(-1) x min(-1)). RESULTS: All doses of prostacyclin and concentrations of nitric oxide resulted in a decrease in mean pulmonary arterial pressure and pulmonary vascular resistance when compared to hypoxic ventilation (p < 0.001) which was independent of the dose or concentration of either drug used. While inhalation of nitric oxide caused a reduction in mean pulmonary arterial pressure back to values obtained during ventilation with FIO(2) 1.0, values achieved with prostacyclin were still significantly higher when compared to measurements prior to the initiation of hypoxic ventilation. However, direct comparison of the effect of 20 ppm nitric oxide and 10 ng x kg(-1) x min(-1) prostacyclin on mean pulmonary arterial pressure revealed no differences between the drugs. All other hemodynamic and gas exchange parameters remained stable throughout the study. CONCLUSIONS: Inhalation of clinically used concentrations of nitric oxide and doses of prostacyclin can decrease elevated pulmonary arterial pressure in an animal model of hypoxic pulmonary vasoconstriction without impairing systemic hemodynamics or gas exchange.

Acute Disease↗
PubMed1999

Combining partial liquid ventilation and prone position in experimental acute lung injury.

BACKGROUND: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS: ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS: The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.

Animals↗
PubMed1999

Nitric oxide inhalation in pulmonary hypertension and severe respiratory failure.

Inhalation of nitric oxide (NO) can cause selective pulmonary vasodilation in aerated lung regions; thus, it may be of benefit in the treatment of various forms of pulmonary hypertension and respiratory distress due to a mismatch of pulmonary ventilation and perfusion. The specific characteristics of inhaled NO exclude long-term treatment, but NO has been successfully used as a test substance to screen patients for response to oral vasodilators. Furthermore, inhalation of NO has been shown to improve gas exchange and right ventricular performance and to reduce the need for other, more invasive therapies in various settings of acute pulmonary hypertension. However, the improvement of arterial oxygenation seen in patients with the acute respiratory distress syndrome does not result in increased survival, questioning the future importance of inhaled NO in the treatment of this pulmonary disorder.

Administration, Inhalation↗
PubMed1999

Fluctuations of inspired concentrations of nitric oxide and nitrogen dioxide during mechanical ventilation.

BACKGROUND: Nitric oxide (NO) is a very reactive agent with potentially toxic oxidation products such as nitrogen dioxide (NO2). Therefore, during NO inhalation a constant inspired concentration and accurate measurement of NO and NO2 concentrations are essential. The objective of this study was to test the NO concentrations at various positions along the inspiratory limb of the breathing circuit using a recently developed system to administer NO in phase with inspiratory flow during mechanical ventilation (Servo 300 NO-A, Siemens, Sweden). Furthermore, we tested whether an active heating system would interfere with inspired NO concentrations. RESULTS: A sharp decline in the NO concentration was found between the respirator's inspiratory outlet and more distal points along the inspiratory limb of the circuit. This finding was most evident when an active heating system was mounted between those points. CONCLUSIONS: The concentrations of NO and NO2 should be measured as near to the patient as possible, as significant fluctuations of these concentrations might be found along the inspiratory limb of the respiratory circuit especially when an active heating system is used.

Journal Article↗
PubMed1998

Superimposing positive end-expiratory pressure during partial liquid ventilation in experimental lung injury.

This study was undertaken to determine the effects of superimposing incremental levels of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) on gas exchange, respiratory mechanics and morphological changes in experimental acute lung injury (ALI). In a prospective trial, six pigs weighing 30+/-5 kg (mean+/-SD) were tracheotomized, submitted to pressure-controlled mechanical ventilation (pc-CMV) and depleted of surfactant by lung lavage. Animals were then mechanically ventilated with three levels of PEEP: 0.5, 1.0 and 1.5 kPa. PLV was then initiated by intratracheal instillation of 30 mL x kg(-1) perfluorocarbon, followed by pc-CMV with PEEP 0.5, 1.0 and 1.5 kPa. Computed tomography (CT)-based analyses of lung volumes and density were obtained after lung lavage, in PLV and during the combined application of PLV and PEEP. Simultaneously, haemodynamics, gas exchange, dynamic compliance (Cdyn) and dynamic resistance (Rdyn) were determined. Statistical analysis was performed using multivariate analyses of variance for repeated measures (p<0.05). In ALI and before PLV, the application of PEEP significantly reduced cardiac output and intrapulmonary shunt. Arterial oxygen tension (Pa,O2) was increased from 6.9 kPa (52 (42, 54) mmHg) (median, (25th and 75th percentile)) to 8.6 kPa (65 (52, 133) mmHg) (PEEP 1.0 kPa) and 15.6 kPa (117 (90, 195) mmHg) (PEEP 15 kPa) (p<0.05). The lung volume obtained by CT increased, CT density was reduced (p<0.05), Cdyn tended to increase and Rdyn to decrease (nonsignificant). PLV increased arterial carbon dioxide tension and reduced pH (p<0.05). CT lung volume and lung density were increased (p<0.05). Superimposing PEEP on PLV increased Pa,O2 from 9.3 kPa (70 (52,124) mmHg) (PEEP 0.5 kPa) to 12.9 kPa (97 (55, 233) mmHg) (PEEP 1.0 kPa) and 403 kPa (303 (64, 426) mmHg) (PEEP 1.5 kPa) (p<0.05), but had no significant effect on CT lung volume and density. It was concluded that in experimental lung injury, positive end-expiratory pressure provided alveolar recruitment. The combined application of positive end-expiratory pressure and partial liquid ventilation significantly augmented oxygenation and might eventually allow either a reduction in the volumes of perfluorocarbons required, or a reduction in positive end-expiratory pressure necessary to maintain pulmonary gas exchange in acute lung injury.

Animals↗
PubMed1997

Right ventricular function in patients treated with inhaled nitric oxide after cardiac surgery for congenital heart disease in newborns and children.

Measurement of right ventricular (RV) function is essential for complete assessment of the effects of inhaled nitric oxide in the postoperative cardiac patient; nitric oxide therapy can result in a decrease in pulmonary vascular resistance and improved echocardiographic RV ejection fraction without necessarily inducing a significant change in pulmonary artery pressure.

Child↗