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Biomedical subjects

F Brasch

Publications and source records attributed to F Brasch.

12 recordsLinked to original sources
PubMed2000

Computed chest tomography in an animal model for decompression sickness: radiologic, physiologic, and pathologic findings.

This study was conducted to investigate the early pulmonary effects of acute decompression in an animal model for human decompression sickness by CT and light microscopy. Ten test pigs were exposed to severe decompression stress in a chamber dive. Three pigs were kept at ambient pressure to serve as controls. Decompression stress was monitored by measurement of pulmonary artery pressure and arterial and venous Doppler recording of bubbles of inert gas. Chest CT was performed pre- and postdive and in addition the inflated lungs were examined after resection. Each lung was investigated by light microscopy. Hemodynamic data and bubble recordings reflected severe decompression stress in the ten test pigs. Computed tomography revealed large quantities of ectopic gas, predominantly intravascular, in three of ten pigs. These findings corresponded to maximum bubble counts in the Doppler study. The remaining test pigs showed lower bubble grades and no ectopic gas by CT. Sporadic interstitial edema was demonstrated in all animals--both test and control pigs--by CT of resected lungs and on histologic examination. A severe compression-decompression schedule can liberate large volumes of inert gas which are detectable by CT. Despite this severe decompression stress, which led to venous microembolism, CT and light microscopy did not demonstrate changes in lung structure related to the experimental dive. Increased extravascular lung water found in all animals may be due to infusion therapy.

Acute Disease↗
PubMed1999

Mapping of capillary flow, cellular redox state, and resting membrane potential in hypoperfused rat myocardium.

The influence on myocyte viability of ischemia-induced changes in capillary perfusion was studied in the hearts of anesthetized rats subjected to partial occlusion of the left coronary artery for 45 min. Timed plasma labeling was applied to determine perfusion patterns. Changes in the fluorescence of preloaded potential-sensitive dyes [tetramethylrhodamine methyl ester (TMRM) and bis-oxonol], of trypan blue, and of endogeneous NADH were utilized in characterizing myocyte viability in histological sections of the heart. Within the hypoperfused zone, localized areas appeared vascularly nonlabeled for periods of at least 10 min. Within these areas a reduction in TMRM fluorescence occurred in 82. 5% of the tissue, signaling a reduced resting membrane potential. In the same areas 37.7% of the myocytes revealed an NADH fluorescence lower than that regularly found in anoxic tissues. This correlated with an especially low level of TMRM, with increased fluorescence bis-oxonol and with an accumulation of trypan blue. In conclusion, in localized hypoperfusion-induced zones lacking capillary flow, an inhomogeneous pattern of reductions in myocyte viability develops, which appears to be relevant in ischemia-induced arrhythmias.

Animals↗
PubMed1999

Quinolines attenuate PAF-induced pulmonary pressor responses and edema formation.

In the present study we have investigated the mechanisms of pulmonary edema caused by platelet-activating factor (PAF) in isolated rat lungs as well as in mice in vivo. In blood-free perfused and ventilated rat lungs, PAF increased lung weight by 0.59 +/- 0.18 g. The cyclooxygenase inhibitor aspirin (500 microM) blocked this response by one-third, and the quinolines quinine (330 microM), quinidine (100 microM), and chloroquine (100 microM) by two-thirds. Lipoxygenase inhibition (10 microM AA861) alone or in combination with thromboxane receptor antagonism (10 microM SQ29548) had no effect on PAF-induced weight gain. In combination with aspirin, quinine or quinidine completely prevented PAF-induced weight gain and the concomitant increase of the capillary filtration coefficient (K(f,c)). Pretreatment with quinine in vivo prevented not only PAF-, but also endotoxin-induced edema formation as assessed by Evans Blue extravasation. In addition, in vivo quinine prevented the endotoxin-induced release of tumor neurosis factor (TNF). Furthermore, in perfused lungs quinine reduced the PAF-induced increases in airway and vascular resistance, as well as thromboxane release. These findings demonstrate the following anti-inflammatory properties of quinolines: reduction of thromboxane and TNF formation; reduction of PAF-induced vasoconstriction and bronchoconstriction; and attenuation of PAF- and lipopolysaccharide (LPS)-induced edema formation. We conclude that the PAF- induced edema consists of two separate mechanisms, one dependent on an unknown cyclooxygenase metabolite, the other one sensitive to quinolines.

Airway Resistance↗
PubMed1998

Ultrastructural pathology of the alveolar type II pneumocytes of human donor lungs. Electron microscopy, stereology, and microanalysis.

Alveolar type II pneumocytes (PII) were studied in 12 human donor lungs perfused with modified Euro-Collins solution during single-lung transplantation (SLTx). While one lung was transplanted, the contralateral donor lung (cDL) was fixed at the time of SLTx for examination by electron microscopy, stereology, and microanalysis. Three groups were then formed: group A (n = 7), cDL without contusions, uneventful early postoperative course; group B (n = 3), cDL with conclusions, uneventful early postoperative course; group C (n = 2), cDL without contusions, early postoperative respiratory dysfunction. The major findings were that the presence of contusions had no effect on PII ultrastructure and that intracellular surfactant-storing lamellar bodies of cDL in group C were characterized by a higher volume-to-surface ratio (VsR) and larger area per cell profile than group A. Correlation analysis based on pooled data (groups A and C) showed that ischaemic time had little effect on PII ultrastructure and bore no relationship to postoperative clinical variables. The duration of preoperative donor intubation had a pronounced influence on ultrastructure and postoperative clinical variables. The stereologically estimated amount of intracellular surfactant and mitochondrial VsR were the only ultrastructural parameters that were significantly associated with early postoperative oxygenation. Lamellar bodies were the only ultrastructural components found to have a significant relationship to postoperative intubation time. The ultrastructural integrity of type II pneumocytes of human donor lungs is an important determinant of early respiratory function following clinical lung transplantation.

Adolescent↗
PubMed1998

Hyperventilation induces release of cytokines from perfused mouse lung.

Artificial mechanical ventilation represents a major cause of iatrogenic lung damage in intensive care. It is largely unknown which mediators, if any, contribute to the onset of such complications. We investigated whether stress caused by artificial mechanical ventilation leads to induction, synthesis, and release of cytokines or eicosanoids from lung tissue. We used the isolated perfused and ventilated mouse lung where frequent perfusate sampling allows determination of mediator release into the perfusate. Hyperventilation was executed with either negative (NPV) or positive pressure ventilation (PPV) at a transpulmonary pressure that was increased 2.5-fold above normal. Both modes of hyperventilation resulted in an approximately 1.75-fold increased expression of tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) mRNA, but not of cyclooxygenase-2 mRNA. After switching to hyperventilation, prostacyclin release into the perfusate increased almost instantaneously from 19 +/- 17 pg/min to 230 +/- 160 pg/min (PPV) or 115 +/- 87 pg/min (NPV). The enhancement in TNFalpha and IL-6 production developed more slowly. In control lungs after 150 min of perfusion and ventilation, TNFalpha and IL-6 production was 23 +/- 20 pg/min and 330 +/- 210 pg/min, respectively. In lungs hyperventilated for 150 min, TNFalpha and IL-6 production were increased to 287 +/- 180 pg/min and more than 1,000 pg/min, respectively. We conclude that artificial ventilation might cause pulmonary and systemic adverse reactions by inducing the release of mediators into the circulation.

Animals↗
PubMed1998

Early alterations in intracellular and alveolar surfactant of the rat lung in response to endotoxin.

The aim of this study was to characterize early ultrastructural, biochemical, and functional alterations of the pulmonary surfactant system induced by Salmonella minnesota lipopolysaccharide (LPS) in rat lungs. Experimental groups were: (1) control in vitro, 150 min perfusion; (2) LPS in vitro, 150 min perfusion, infusion of 50 microg/ml LPS after 40 min; (3) control ex vivo, 10 min perfusion; (4) LPS ex vivo, lungs perfused for 10 min from rats treated for 110 min with 20 mg/kg LPS intraperitoneally. Morphometry of type II pneumocytes showed that LPS increased stored surfactant. Lamellar bodies were increased in size, but decreased in numerical density, suggesting that giant lamellar bodies observed in LPS-treated lungs may result from fusion of normal bodies. Structural analysis of alveolar surfactant composition showed that LPS elicited an increase in lamellar body-like and multilamellar forms. Bronchoalveolar lavage (BAL) material from LPS-treated lungs was decreased in phospholipids. BAL bubble surfactometer analysis showed a reduction in hysteresis area caused by LPS. We conclude that LPS leads to alterations of intracellular and alveolar surfactant within 2 h: fusion of lamellar bodies, reduction in surfactant secretion, and changes in alveolar surfactant transformation, composition, and function, which may contribute to the development of respiratory distress.

Animals↗
PubMed1996

Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

BACKGROUND: Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. MATERIALS AND METHODS: Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. RESULTS: LPS induced the release of TX and caused increased airway resistance after about 30 min. Both TX formation and LPS-induced bronchoconstriction were prevented by treatment with the unspecific COX inhibitor acetyl salicylic acid, the specific COX-2 inhibitor CGP-28238, dexamethasone, actinomycin D, or cycloheximide. LPS-induced bronchoconstriction was also inhibited by the TX receptor antagonist BM-13177. The TX-mimetic compound, U-46619, increased airway resistance predominantly by constricting terminal bronchioles. COX-2-specific mRNA in lung tissue was elevated after LPS exposure, and this increase was attenuated by addition of dexamethasone or of actinomycin D. In contrast to LPS, platelet-activating factor (PAF) induced immediate TX release and bronchoconstriction that was prevented by acetyl salicylic acid, but not by CGP-28238. CONCLUSIONS: LPS elicits the following biochemical and functional changes in rat lungs: (i) induction of COX-2; (ii) formation of prostaglandins and TX; (iii) activation of the TX receptor on airway smooth muscle cells; (iv) constriction of terminal bronchioles; and (v) increased airway resistance. In contrast to LPS, the PAF-induced TX release is likely to depend on COX-1.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Morphometric characterisation of the fine structure of human type II pneumocytes.

BACKGROUND: Pulmonary type II pneumocytes have been examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and morphometry in numerous mammals. Until now, the fine structure of the human type II pneumocyte has not been studied by means of morphometry. METHODS: Eleven human donor lungs, which could not be made available for a suitable recipient, were preserved with Euro Collins solution (ECS) according to clinical organ preservation techniques. The lungs were fixed via the airways. Systematic random samples were analyzed by SEM, TEM, and classical stereological methods. RESULTS: Type II pneumocytes showed normal fine structural characteristics. Morphometry revealed that although inter-individual variation due to some oedematous swelling was present, the cells were in a normal size range as indicated by an estimated mean volume of 763 +/- 64 microns 3. The volume densities were: nucleus 21.9 +/- 2.2%, mitochondria 5.8 +/- 0.9%, lamellar bodies 9.8 +/- 3.6%, and remaining cytoplasmic components 62.4 +/- 2.9% of the cell volume. Since the inter-individual variations in the volume densities referred to the cell may, to variable degrees, reflect the variation in the reference space, the volume densities referred to the constant test point system and the respective volume-to-surface ratios were used for inter-individual comparisons. These parameters indicate that lamellar bodies were independent of cellular swelling, while mitochondria < nucleus < remaining cytoplasmic components increased in size with increasing cell size. CONCLUSIONS: Two to 7.5 hours of cold ischemia following ECS preservation do not deteriorate the fine structure of type II pneumocytes of human donor lungs. For reliable assessment of fine structural variations, morphometric parameters are required that are independent of variations in cell size.

Cell Nucleus↗
PubMed1995

Functional and fine structural changes in isolated rat lungs challenged with endotoxin ex vivo and in vitro.

The aim of this study was to relate changes in rat lung functions caused by the endotoxin lipopolysaccharide (LPS) to alterations in structure. The following four experimental groups were used: 1), control in vitro, perfusion for 150 minutes; 2), LPS in vitro, perfusion for 150 minutes and infusion of 5 mg of LPS after 40 minutes; 3), control ex vivo, perfusion for 10 minutes; and 4), LPS ex vivo, lungs perfused for 10 minutes from rats treated for 110 minutes with 20 mg/kg LPS intraperitoneally. Histologically, blood-derived leukocytes were detectable only in lungs from group 4, where neutrophils were found in capillaries, interstitium, and endothelial pouches. LPS treatment increased pulmonary resistance and decreased pulmonary compliance in group 4 (ex vivo), and, to a greater extent, in group 2 (in vitro). In these two groups, formation of giant lamellar bodies in the type II pneumocytes was observed. By histological examination, the bronchoconstriction induced by LPS in vitro was localized to the terminal bronchioles. At 2 hours after LPS treatment, no edema and no change in precapillary and postcapillary resistance, capillary pressure, vascular compliance, capillary permeability, and the wet/dry ratio was observed. Thus, our major findings are that LPS induced constriction of the terminal bronchioles in vitro, formation of giant lamellar bodies in type II pneumocytes ex vivo and in vitro, and trapping of neutrophils in endothelial pouches in vivo.

Animals↗
PubMed1994

Evaluation of lanthanide tracer methods in the study of mammalian pulmonary parenchyma and cardiac muscle by electron energy-loss spectroscopy.

Lanthanum (La) has widely been used as a tracer to study the integrity of plasma membranes. With conventional transmission electron microscopy (cTEM), the absence of electron scattering deposits from the cytoplasm has generally been assumed to reflect an intact cell membrane. However, the application of electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) reveals that electron scattering deposits may be present which do not contain La. However, La could be detected in regions of pulmonary parenchyma and cardiac muscle that were devoid of electron scattering deposits. Therefore, to exclude misinterpretations based on cTEM the application of microanalytical techniques is strongly recommended for the study of the integrity of plasma membranes by means of La tracers. In addition, ESI and EELS are shown to distinguish between different tracers in simultaneous applications of La and terbium (Tb) which were used at the different faces of the pulmonary air-blood barrier. The analysis of the distribution of both tracers which form electron scattering deposits, indistinguishable by cTEM, may help us to understand the different functional significances of cellular alterations of both cellular borders of the barrier. As was shown for La, however, strictly controlled conditions are mandatory during the fixation procedure because an increase in the incubation time to more than 1 h in samples of pulmonary parenchyma may result in the occurrence of La deposits within the cytoplasm. In the absence of electron scattering deposits, the presence of La in glycogen granules and ribosome-containing areas of various types of alveolar septal cells even after 15 min incubation indicates that the absence of deposits does not necessarily correspond to the absence of the tracer.

Animals↗
PubMedDate not supplied

Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.

Adult↗