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Biomedical subjects

U Pison

Publications and source records attributed to U Pison.

At least 37 records · Page 2Linked to original sources
PubMed1993

Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange.

Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that participates in the regulation of vascular tone. We studied the effects of inhaled NO gas on transient hypoxic pulmonary vasoconstriction and normal lungs in mechanically ventilated sheep. We measured hemodynamics and pulmonary gas exchange. For gas exchange measurements we used conventional blood gas analysis and the multiple inert gas elimination technique to estimate ventilation-perfusion heterogeneity. Our hypotheses were 1) inhaled NO reverses hypoxic pulmonary vasoconstriction, 2) the hemodynamic effects of inhaled NO are limited to the pulmonary circulation, and 3) inhaled NO does not impair pulmonary gas exchange and may redistribute blood flow to better ventilated areas of the lungs. Hypoxic pulmonary vasoconstriction was induced by using a hypoxic inspiratory gas mixture. The addition of 20 ppm NO to the hypoxic inspiratory gases returned pulmonary arterial pressure to baseline values. Systemic hemodynamics and gas exchange indexes derived from conventional blood gas analysis remained constant. Gas exchange indexes for ventilation-perfusion ratios and gas dispersions improved. The addition of 20 ppm NO to medical air (21% O2) had no such significant effects on hemodynamics or pulmonary gas exchange. Our findings show that inhaled NO reverses transient hypoxic pulmonary vasoconstriction. The hemodynamic effects of NO are limited to the pulmonary circulation; it does not impair pulmonary gas exchange. Moreover, it redistributes blood flow to better ventilated alveoli. As such, NO has potential in the treatment of lung diseases associated with pulmonary hypertension.

Administration, Inhalation↗
PubMed1993

Inhaled nitric oxide: its effects on pulmonary circulation and airway smooth muscle cells.

Nitric oxide (NO), an endothelium-derived relaxing factor synthesized from L-arginine by the enzyme NO synthase, has been identified as an important, short-acting, endogenous vasodilator. In patients with pulmonary hypertension, inhaling a low dose of NO as a gaseous vasodilator has been shown to induce selective vasodilation in ventilated lung areas. It achieves this without the disadvantages attributed to systemically infused vasodilators e.g. systemic vasodilation and an increase in pulmonary right-to-left shunt with a consecutive fall in PaO2. Thus, inhaled NO reduces pulmonary hypertension in the severe adult respiratory distress syndrome and in persistent pulmonary hypertension of the newborn, and improves arterial oxygenation by redistributing pulmonary blood flow away from the shunt and towards areas with almost normal ventilation/perfusion ratios. The bronchodilatory effect of NO may be an alternative therapy for treating asthma and bronchospasm.

Administration, Inhalation↗
PubMed1992

Surfactant protein A (SP-A) is decreased in acute parenchymal lung injury associated with polytrauma.

To further investigate if the pulmonary surfactant system is altered in acute parenchymal lung injury of adults following polytrauma we measured SP-A level and phospholipid composition in 150 sequentially obtained lung lavage samples from poly-traumatized patients (n = 19) beginning at the day of trauma and ending 18 days later or when the patient was extubated. Out of the 19 patients studied 10 had severe parenchymal lung injury (ARDS), nine had moderate lung injury. SP-A was measured using a two-monoclonal sandwich ELISA-assay. Phospholipids were separated using high-performance liquid chromatography and their composition was calculated by comparison with standard phospholipid mixtures. We found immunoreactive SP-A concentrations ranging from 0.1 micrograms ml-1 to 8.5 micrograms ml-1 lung lavage fluid obtained from all patients. The mean SP-A concentration in patients who had severe parenchymal lung injury (ARDS) was 1.06 +/- 0.16 micrograms ml-1 lavage fluid, the mean concentration in patients who had only moderate parenchymal lung injury was 1.92 +/- 0.18 micrograms ml-1 lavage fluid. Both concentrations were lower than in healthy controls (2.74 +/- 0.3 micrograms ml-1 lavage fluid; n = 12). In patients who had moderate lung injury the SP-A level normalized, but in patients who had severe lung injury the SP-A level remained low during the timespan examined. SP-A alterations did not correlate to changes in phospholipid composition as determined in lung lavage samples of individual patients. We conclude that alveolar SP-A concentrations decrease in polytraumatized patients who have acute parenchymal lung injury soon after the trauma occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Specific binding of surfactant apoprotein SP-A to rat alveolar macrophages.

Surfactant protein A (SP-A) influences the function of alveolar macrophages in vitro. In this study the characteristics of the binding of 125I-labeled SP-A to rat alveolar macrophages has been investigated. The binding of SP-A to alveolar macrophages at 4 degrees C was saturable with half-maximal binding at a SP-A concentration of 4 micrograms/ml. Bound SP-A was rapidly displaced by an excess of unlabeled SP-A. The binding of labeled SP-A to the alveolar macrophages was blocked in a dose-dependent fashion by unlabeled SP-A, the collagen-like protein C1q and type V collagen but not by bovine serum albumin. These results suggest that a component of the interaction between SP-A and alveolar macrophages is mediated through the collagen-like domain of SP-A and that the characteristics of this interaction are consistent with there being a specific receptor for SP-A on the surface of alveolar macrophages.

Animals↗
PubMed1991

Procoagulant activity in bronchoalveolar lavage of severely traumatized patients--relation to the development of acute respiratory distress.

In a prospective study in severely traumatized patients, procoagulant activity (PCA) was determined in bronchoalveolar lavage fluids (BAL). Bronchoscopy with lavage was serially performed during the first 15 days after injury (in total 148 samples of 25 patients). PCA was measured as recalcification times in the absence or presence of excess phosphatidylethanolamine and translated into procoagulant unit equivalents using standard thromboplastin. The data were correlated to the extent of respiratory failure in the injured patients and were compared to PCA in 29 lavage samples obtained from 10 healthy control subjects. A several-fold increase in BAL PCA was noted in all trauma victims, evident already within the first 24 h after injury. A progressive rise in PCA occurred from the 4th posttraumatic day and was highly significantly more pronounced in patients developing serious respiratory failure than in those with only mild pulmonary dysfunction. Significant correlations were noted between PCA increase and alveolar protein-leakage, granulocyte-influx and surfactant alterations, however with correlation coefficients not surpassing 0.55. We conclude that a marked increase in procoagulant activity occurs in severely injured patients, which may favour alveolar fibrin deposition and is related to the development of acute respiratory failure.

Blood Coagulation Factors↗
PubMed1990

Surfactant abnormalities and adult respiratory failure.

Surfactant abnormalities have been implicated in the development of the acute respiratory distress syndrome in adults. Experimental studies show that surfactant inhibition by protein-leak into the alveolar space is of major importance under these circumstances. Fibrin(ogen)-surfactant-interaction appears to contribute to disturbances of surfactant function with subsequent alveolar instability and ventilation-perfusion-mismatch. In a prospective study in severely injured patients, the surfactant in serially obtained bronchoalveolar lavage fluids was investigated. An early leakage of plasma proteins into the alveolar space was noted in those patients, who developed severe ARDS. Moreover, deterioration of surfactant function was markedly more pronounced in those patients than in trauma victims who developed only mild pulmonary dysfunction. In addition to the protein-leakage, a progressive decrease of the surfactant-specific dipalmitoyl-phosphatidylcholine was noted, significantly correlated with the deterioration of surfactant function and the severity of respiratory failure. In conclusion, experimental and clinical studies show surfactant abnormalities in the adult respiratory distress syndrome. Plasma protein-leakage and progressive alteration of alveolar type II surfactant secretion appear to be of major importance.

Adult↗
PubMed1990

Altered pulmonary surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure.

Pulmonary surfactant, which is crucial for alveolar stability, may also be involved in endogenous defense mechanisms of the lungs. Thus, alterations in pulmonary surfactant may promote infections, including pneumonia and septicemia. Because patients who have acute respiratory failure often develop pneumonia, thus septicemia, we investigated when surfactant is altered in these patients and whether there is a specific pattern of changes in surfactant phospholipid composition associated with septicemia in these patients. To answer these questions, we determined the phospholipid content and composition in lung washings obtained from alveolar sites (by bronchoalveolar lavage) and from tracheal sites (by aspiration). Both techniques were performed serially over a period of 18 days in 30 patients who had acute respiratory failure resulting from polytrauma, 18 of whom developed septicemia caused by pneumonia. We found that in lung washings obtained from the alveolar sites from all patients, the phosphatidylglycerol content was decreased and the phosphatidylinositol content was increased as early as 6 hr after trauma and normalized during recovery of the patients. In addition, alveolar phosphatidylcholine content was decreased 24 hr after trauma. In patients who developed septicemia during the observation time, but not in patients who had uncomplicated courses of acute respiratory failure, the concentrations of alveolar phosphatidylethanolamine (normally 4.8% of total phospholipids) and alveolar phosphatidylcholine (normally 62.8%) both approached the proportions found in the trachea (phosphatidylethanolamine 33.4%, phosphatidylcholine 35.6%), suggesting that surfactant phospholipid pool size had progressively decreased. Our results indicate that in patients who have acute respiratory failure, pulmonary surfactant is altered very early, and that when septicemia complicates the course of acute respiratory failure, the surfactant phospholipid pool size decreases progressively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Proteolytic inactivation of dog lung surfactant-associated proteins by neutrophil elastase.

The adsorption of pulmonary surfactant to an air/fluid interface is influenced by calcium-dependent interactions between its lipid and protein components. The latter include a glycoprotein of 28-36 kDa (SP-A) and two smaller hydrophobic proteins of 5-8 kDa (SP-B, SP-C). Neutrophil elastase and other proteolytic enzymes found in the alveolar washings in a variety of acute lung injuries may cleave the protein components of lung surfactant. To examine the hypothesis that free airspace elastolytic activity may thereby impair surfactant function, we analyzed the effect of neutrophil elastase on surfactant activity in vitro. The adsorption characteristics of dog surfactant and of complexes reassembled from purified surfactant components were examined after incubations with active or heat-inactivated neutrophil elastase. Surfactant preincubated with the active enzyme showed a marked concentration-dependent slowing of adsorption associated with proteolytic cleavage of SP-A. To determine whether elastase also decreases surface activity by affecting the hydrophobic proteins SP-B and SP-C, we studied the effect of incubating elastase with liposomes prepared from surfactant lipid fractions which contain SP-B and SP-C. The addition of intact SP-A to these liposomes incubated with inactive enzyme immediately enhanced adsorption speed. This enhancement was greatly attenuated in liposomes treated with active elastase, suggesting that one or both of the hydrophobic surfactant proteins had been affected by elastase. We conclude that proteolytic cleavage of surfactant proteins reduces adsorption speed in vitro and may disturb surfactant function in vivo.

Animals↗
PubMed1989

Surfactant abnormalities in patients with respiratory failure after multiple trauma.

We present a prospective study, designed to evaluate surfactant abnormalities in severely injured patients during the course of post-traumatic pulmonary dysfunction. Serially obtained bronchoalveolar lavage fluids from noncontused lung areas (in total, 132 samples from 17 patients) were analyzed for alveolar phospholipid composition and surfactant function in vitro during the first 14 days after trauma. The data were compared with those of 29 lavage samples obtained from 10 healthy control subjects and correlated to severity of respiratory failure. In the traumatized patients, the total lavage phospholipid content was unchanged, but there was a progressive decrease in the relative amounts of phosphatidylcholine (%PC) and phosphatidylglycerol and an increase in phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin. These alterations were paralleled by a marked decrease in the hysteresis area of the surface tension isotherm. The decrease in %PC and reduction of hysteresis area were significantly correlated. The alterations in alveolar phospholipid composition and in vitro surfactant function were more pronounced in patients with severe respiratory failure. There was a significant inverse correlation between severity of respiratory dysfunction and %PC or hysteresis area for all traumatized patients. Protein leakage into the alveolar space was significantly higher in patients with severe respiratory failure and appeared to precede surfactant abnormalities in such patients. The neutrophil content in the alveolar space was markedly increased in all patients with multiple injuries however, no significant correlation with the noted alterations in alveolar phospholipid composition or surfactant function was found. We concluded that surfactant abnormalities occur during the course of post-traumatic pulmonary dysfunction and are correlated with the severity of respiratory failure.

Adolescent↗
PubMed1988

Distribution and function of alveolar cells in multiply injured patients with trauma-induced ARDS.

To determine whether alveolar cells are involved in the pathogenesis of adult respiratory distress syndrome (ARDS), we assessed the distribution and function of alveolar cells from 30 polytraumatized patients with trauma-induced respiratory failure, 5 of whom also had lung contusion. Cells were obtained by bronchoalveolar lavage performed daily beginning on the day of trauma and continuing for 14 days. Neutrophils constituted about 60% of lavage cells in ARDS patients with lung contusion 0-2 days after polytrauma and about 50% in ARDS patients without lung contusion. In ARDS patients with lung contusion the neutrophil fraction decreased to 52% 3-6 days after trauma and to 40% 7-14 days after trauma. In patients without lung contusion the neutrophil fraction increased to 77% and then decreased to 60% at these times. Total cell counts in ARDS patients with lung contusion were more than twice as high as in patients without lung contusion 0-2 days after trauma. The difference in total cell counts decreased during days 3-6 and disappeared by day 7. In all patients morphologically altered alveolar cells were observed 4 days and more after trauma. In non-survivors significantly more altered cells were found. The chemiluminescence-response pattern of the alveolar cells was enhanced throughout the study and correlated with the neutrophil fraction (r = 0.6). The neutrophil fraction also correlated with the pulmonary vascular resistance during the first two days after trauma (r = 0.53). We conclude that alveolar cells are involved in the pathogenesis of trauma-induced ARDS and that the alveolar cell distribution is different in patients with and without lung contusion during the development of posttraumatic respiratory failure.

Acute Disease↗
PubMed1987

[Normal values of cell distribution and function in the human alveolus. Bronchoalveolar lavage as a diagnostic tool in intensive care medicine].

The cell distribution and cell function in the normal human alveolar were determined in 23 healthy subjects by obtaining the pulmonary lavage fluid from bronchoalveolar lavage. A uniform alveolar cell spectrum was found. (Alveolar macrophages 95-98%, polymorphonuclear neutrophils 2-3%, lymphocytes 0-2%.) The cell systems reacted reproducibly to a defined phagocytosis stimulation in luminol-enhanced chemoluminescence. The phospholipid lung profile, which is important for the function of the surfactant, was determined by means of high-pressure liquid chromatography. The typical inflammation mediators were not present in the humoral spectrum of the supernatant part of the lavage fluid. Albumin, transferrin, and alpha-1-antitrypsin were regularly seen in healthy adults in the bronchoalveolar lavage fluid. The results supply the basis for the interpretation of the findings in polytraumatised patients in adult respiratory distress syndrome.

Acute-Phase Proteins↗
PubMed1986

High-performance liquid chromatography of adult human bronchoalveolar lavage: assay for phospholipid lung profile.

High-performance liquid chromatography has been used to separate pulmonary phospholipids from adult human bronchoalveolar lavage. A solvent system consisting of acetonitrile-water (80:20) as solvent A and pure acetonitrile as solvent B was used with a silica column (Bio-Sil HP 10) coupled to an Si-100 Polyol precolumn. A linear gradient from 87.5 to 25% of solvent B was found to separate all biologically relevant surfactant phospholipids in the following sequence and composition: phosphatidic acid (1.1%), phosphatidylglycerol (10.6%), phosphatidylinositol (9.9%), phosphatidylethanolamine (3.6%), phosphatidylserine (4.5%), phosphatidylcholine (60.8%), sphingomyelin (8.1%) and lysophosphatidylcholine (1.6%). These results were very similar to the phospholipid pattern obtained by two-dimensional thin-layer chromatography. It is concluded that high-performance liquid chromatography is a useful and rapid method for the separation of phospholipids in biological fluids containing pulmonary surfactant.

Adult↗
PubMed1985

[Bronchoalveolar lavage as a diagnostic method in intensive therapy].

Bronchoalveolar lavage is presented as a standardised diagnostic method in the clarification of interstitial pulmonary changes in the acute respiratory distress syndrome (ARDS). Its justification is based on the fact that changes in lung biopsies are reflected by early changes in the composition of the rinse and in the ability of the cellular components to function properly, independent of the origin of the immunological processes in ARDS. Pulmonary function is not adversely affected by the procedure provided it is carried out "lege artis". We hope that it will be possible in future to achieve early detection of a developing progressive failure of pulmonary function, by employing early markers. The procedure also allows continual follow-up of the success of an initiated therapy.

Bronchoscopy↗