[Intravenous perfluorocarbons: 30 years of research--what now?].
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Animals↗
Biomedical subjects
M Max
Publications and source records attributed to M Max.
Effect of inhaled nitric oxide in combination with almitrine on ventilation-perfusion distributions in experimental lung injury.
OBJECTIVE: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V(A)/Q) ratio. DESIGN: Prospective, controlled animal study. SETTING: Animal research facility of a university hospital. INTERVENTIONS: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 microg/kg per min ALM, 3) 1 microg/ kg per min ALM. For each condition, gas exchange, hemodynamics and V(A)/Q distributions were analyzed using the multiple inert gas elimination technique (MIGET). MEASUREMENT AND RESULTS: With NO + ALM, arterial oxygen partial pressure (PaO2) increased from 63 +/- 18 mmHg to 202 +/- 97 mmHg while intrapulmonary shunt decreased from 50 +/- 15 % to 26 +/- 12% and blood flow to regions with a normal V(A)/Q ratio increased from 49 +/- 16 % to 72 +/- 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05). CONCLUSIONS: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V(A)/Q relationships.
Administration, Inhalation↗
[Pulmonary gas exchange in anesthesia].
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Anesthesia↗
Effect of PEEP and inhaled nitric oxide on pulmonary gas exchange during gaseous and partial liquid ventilation with small volumes of perfluorocarbon.
BACKGROUND: Partial liquid ventilation, positive end-expiratory pressure (PEEP) and inhaled nitric oxide (NO) can improve ventilation/perfusion mismatch in acute lung injury (ALI). The aim of the present study was to compare gas exchange and hemodynamics in experimental ALI during gaseous and partial liquid ventilation at two different levels of PEEP, with and without the inhalation of nitric oxide. METHODS: Seven pigs (24+/-2 kg BW) were surfactant-depleted by repeated lung lavage with saline. Gas exchange and hemodynamic parameters were assessed in all animals during gaseous and subsequent partial liquid ventilation at two levels of PEEP (5 and 15 cmH2O) and intermittent inhalation of 10 ppm NO. RESULTS: Arterial oxygenation increased significantly with a simultaneous decrease in cardiac output when PEEP 15 cmH2O was applied during gaseous and partial liquid ventilation. All other hemodynamic parameters revealed no relevant changes. Inhalation of NO and instillation of perfluorocarbon had no additive effects on pulmonary gas exchange when compared to PEEP 15 cmH2O alone. CONCLUSION: In experimental lung injury, improvements in gas exchange are most distinct during mechanical ventilation with PEEP 15 cmH2O without significantly impairing hemodynamics. Partial liquid ventilation and inhaled NO did not cause an additive increase of PaO2.
Administration, Inhalation↗
Remifentanil and propofol for sedation in children and young adolescents undergoing diagnostic flexible bronchoscopy.
Flexible fibreoptic bronchoscopy (FOB) has become a useful diagnostic and therapeutic procedure in children. We investigated 26 patients (3-14 years) for FOB using a new sedation strategy. All patients received oral premedication and inhalation of topical anaesthetic. Sedation for bronchoscopy was achieved with a continuous infusion of remifentanil and intermittent boluses of propofol. Propofol injection was repeated if sedation was inadequate. Sedation could be successfully performed in all children without adverse effects. Endtidal CO2 concentration and arterial oxygen saturation remained stable throughout the study. All children were awake 5+/-1.3 min after stopping remifentanil infusion. Sedation with remifentanil/propofol is a new sedation strategy for diagnostic flexible paediatric bronchoscopy in children with spontaneous ventilation.
Adolescent↗
Effect of artificial valves on intestinal adaptation in the short-bowel syndrome: an integrated study of morphological and functional changes in rats.
Two-third-resections of the proximal or distal small bowel with and without artificial valves were performed in rats. Intestinal adaptation led to a significant increase in bowel diameter, villus height and villus diameter and consequently in absorptive mucosal surface area per unit of serosal area. Additional artificial valve construction did not affect the calculated mucosal surface area after proximal resection, while it significantly decreased the absorptive area by the occurrence of large, plump villi after distal resection. There was no change in small-intestinal absorption of water, glucose and electrolytes per unit mucosa with valve construction. DNA cytometry showed that artificial valves led to mucosal hyperplasia without hypertrophy. These morphological changes coincided with a significant increase in basal and stimulated gastrin release. The body weight was unchanged or even worse in the valve groups than after resection alone, despite a significantly prolonged transit time. Therefore, in our study, artificial valves did not result in functional improvements after small intestinal resections.
Adaptation, Physiological↗
Photochemistry of the primary event in short-wavelength visual opsins at low temperature.
Two short-wavelength cone opsins, frog (Xenopus laevis) violet and mouse UV, were expressed in mammalian COS1 cells, purified in delipidated form, and studied using cryogenic UV-vis spectrophotometry. At room temperature, the X. laevis violet opsin has an absorption maximum at 426 nm when generated with 11-cis-retinal and an absorption maximum of 415 nm when generated with 9-cis-retinal. The frog short-wavelength opsin has two different batho intermediates, one stable at 30 K (lambda(max) approximately 446 nm) and the other at 70 K (lambda(max) approximately 475 nm). Chloride ions do not affect the absorption maximum of the violet opsin. At room temperature, mouse UV opsin has an absorption maximum of 357 nm, while at 70 K, the pigment exhibits a bathochromic shift to 403 nm with distinct vibronic structure and a strong secondary vibronic band at 380 nm. We have observed linear relationships when analyzing the energy difference between the initial and bathochromic intermediates and the normalized difference spectra of the batho-shifted intermediates of rod and cone opsins. We conclude that the binding sites of these pigments change from red to green to violet via systematic shifts in the position of the primary counterion relative to the protonated Schiff base. The mouse UV cone opsin does not fit this trend, and we conclude that wavelength selection in this pigment must operate via a different molecular mechanism. We discuss the possibility that the mouse UV chromophore is initially unprotonated.
Absorption↗
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↗
Comparison of the breathing workload imposed by different ventilators.
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Humans↗
[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↗
The necessity of performing transesophageal echocardiography in patients with acute respiratory distress syndrome.
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Echocardiography, Transesophageal↗
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↗
Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium.
Gustducin is a transducin-like G protein selectively expressed in taste receptor cells. The alpha subunit of gustducin (alpha-gustducin) is critical for transduction of responses to bitter or sweet compounds. We identified a G-protein gamma subunit (Ggamma13) that colocalized with alpha-gustducin in taste receptor cells. Of 19 alpha-gustducin/Ggamma13-positive taste receptor cells profiled, all expressed the G protein beta3 subunit (Gbeta3); approximately 80% also expressed Gbeta1. Gustducin heterotrimers (alpha-gustducin/Gbeta1/Ggamma13) were activated by taste cell membranes plus bitter denatonium. Antibodies against Ggamma13 blocked the denatonium-induced increase of inositol trisphosphate (IP3) in taste tissue. We conclude that gustducin heterotrimers transduce responses to bitter and sweet compounds via alpha-gustducin's regulation of phosphodiesterase (PDE) and Gbetagamma's activation of phospholipase C (PLC).
Amino Acid Sequence↗
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↗
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↗
Light-dependent activation of rod transducin by pineal opsin.
The pineal gland expresses a unique member of the opsin family (P-opsin; Max, M., McKinnon, P. J., Seidenman, K. J., Barrett, R. K., Applebury, M. L., Takahashi, J. S., and Margolskee, R. F. (1995) Science 267, 1502-1506) that may play a role in circadian entrainment and photo-regulation of melatonin synthesis. To study the function of this protein, an epitope-tagged P-opsin was stably expressed in an embryonic chicken pineal cell line. When incubated with 11-cis-retinal, a light-sensitive pigment was formed with a lambdamax at 462 +/- 2 nm. P-opsin bleached slowly in the dark (t1/2 = 2 h) in the presence of 50 mM hydroxylamine. Purified P-opsin in dodecyl maltoside activated rod transducin in a light-dependent manner, catalyzing the exchange of more than 300 mol of GTPgammaS (guanosine 5'-O-(3-thiotriphosphate))/mol of P-opsin. The initial rate for activation (75 mol of GTPgammaS bound/mol of P-opsin/min at 7 microM) increased with increasing concentrations of transducin. The addition of egg phosphatidylcholine to P-opsin had little effect on the activation kinetics; however, the intrinsic rate of decay in the absence of transducin was accelerated. These results demonstrate that P-opsin is an efficient catalyst for activation of rod transducin and suggest that the pineal gland may contain a rodlike phototransduction cascade.
Animals↗
[Weaning from artificial respiration. 2].
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Humans↗
[Perspectives in mechanical ventilation in ARDS].
Despite more than 25 years of extensive research, the mortality of ARDS patients remains high. The inflammatory process within the lung and the associated gas exchange disturbances require an aggressive ventilatory regimen, which itself may harm the lung. Therapeutic measures which are used to reduce iatrogenic damage to the lung are pressure controlled mechanical ventilation in combination with PEEP and permissive hypercapnia, dehydration and extracorporeal gas exchange. At present, new strategies such as intratracheal instillation of surfactant, partial liquid ventilation and inhalation of nitric oxide (NO) are being evaluated. Surfactant reduces the surface tension, forming a monomolecular layer at the air/tissue interface. It thereby decreases the forces necessary to expand the alveoli and prevents alveoli with small diameter from collapsing. In ARDS, a disturbance of surfactant synthesis, function and re-uptake is the rationale for treatment with exogenous surfactant. Initial clinical results suggest a limited positive effect independently of the surfactant preparation used, the dose and the application mode. Experience with partial liquid ventilation with perfluorocarbons in ARDS has also been reported. Perfluorocarbons are liquids with a high binding capacity for oxygen and carbon dioxide. During normal mechanical ventilation with gas, repetitive doses of perfluorocarbons are instilled into the lungs up to a volume equal to the functional residual capacity. The liquid is pushed into collapsed alveoli and keeps them open by reducing the surface tension. First clinical studies have demonstrated the possible improvement in pulmonary gas exchange. In ARDS, inhalation of NO may cause a predominantly selective vasodilation in blood vessels of ventilated lung regions, resulting in an increase in PaO2 and a decrease in pulmonary artery pressure. The effect of NO on the pulmonary vasculature also induces a reduction in right ventricular afterload and also in pulmonary capillary pressure, which may lead to a faster resolution of pulmonary edema. However, in spite of the promising results of these new strategies, further studies are needed to evaluate their influence on morbidity and mortality.
Combined Modality Therapy↗