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  • 1
    ISSN: 1432-0738
    Keywords: Dichlorvos ; Acetylcholinesterase ; Bronchial tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The experiments presented here deal with the effects of the inhalation of dichlorvos [dimethyl-(2,2 dichlorvinyl)-phosphate, DDVP] vapor on acetyl-cholinesterase (ACHE) activity in rat bronchial tissue. Exposure to DDVP concentrations of 0.8 and 1.8 μg/l for 3 days reduced ACHE activity in the bronchial tissue (62.8±0.8 and 51.6±1.6% of the control), but did not elicit any changes in blood ACHE activity (101±4.5% of the control each). Higher concentrations (4.3 μg/l) induced a decline in ACHE activity also in the blood (38.2±1.1% of the control). In the histochemical preparations used to demonstrate CHE activity in bronchial tissue (thiolacetic acid method), a staining of the bronchial glands and smooth muscles characteristic of the enzyme activity was strongly reduced after exposure of the animals to even the lowest dose applied (0.2 μg/l). The question of whether localized inhibition of ACHE in the bronchial tissue might cause increases in airway resistance due to activation of a broncho-bronchial reflex is discussed. This efferent cholinergic mechanism has been found to be at least partly responsible for maintenance of bronchospasm and hypersecretion in chronic obstructive deseases of the respiratory system.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 263-275 
    ISSN: 1432-1912
    Keywords: Vasodilator Agents ; Oxygen Consumption ; Blood Flow ; Hindlimb ; Sympathectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of various vasodilating agents on the oxygen consumption was studied in the hindlimb of the cat. During the increase in flow by means of papaverine, acetylcholine, bradykinin, cobaltous chloride, isoprenaline, and phentolamine, an initial increase in the oxygen consumption for about 30 to 60 sec was observed. This phase was immediately followed by a sustained reduction in oxygen uptake below the control value although the blood flow remained increased. The diminution was greater than the initial elevation in oxygen uptake and was correlated with the increase in blood flow. An inhibition of the sympathetic constrictor nerve activity did not influence the biphasic changes in oxygen consumption due to the vasodilating agents. The blockade of the sympathetic vasoconstrictor tone led itself to a vasodilation, which was accompanied by an elevation of oxygen uptake during the whole period of flow increase. It is suggested that a shift in the pattern of flow within the extremity is responsible for these changes in oxygen consumption following the administration of the vasodilating agents tested here.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 99-106 
    ISSN: 1432-1912
    Keywords: Lung perfusion ; Bupivacaine ; Fluorochrome-labeled capillaries ; First-pass retention ; Inulin ; Tritium-labeled water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of rat lung to remove the local anaesthetic drug bupivacaine from the blood was studied in isolated organs which were perfused either in an open (single-pass mode) or in a closed system (recirculating medium). Isolated perfused rat lungs exhibited a very low capacity to metabolize bupivacaine within 3 h during which the drug circulated continuously through the organ. The clearance values differed only by 0.2 ml/min from the control parameters in sham perfusions. The calculated extraction ratio was 0.2% and the elimination half-life was about 210 min. The volume of distribution of bupivacaine was 133 ml which remarkably surmounted the reference values obtained for sham perfusions. The distribution of bupivacaine into the pulmonary tissue was investigated applying the multiple indicator dilution technique to isolated lungs perfused in the single-pass mode. The mean elimination time of model compounds for distribution into the intravascular space, 14C-inulin, and the total water space, 3H-water, were 68 and 75 s at a flow rate of 6 ml/min. The volume of distribution was 5.9 ml for inulin and 6.5 ml for water. The mean transit time for concomitantly injected bupivacaine was 221 s and the volume of distribution was 14.4 ml. The respective parameters of sham perfusions performed without an isolated organ were substantially lower, i.e. mean elimination time 50, 50 and 61 s and distribution volume 4.9, 5.0 and 6.1 ml for inulin, water and bupivacaine. The volume of distribution during single-pass contact of bupivacaine to lung was not substantially influenced by an increase of the flow rate from 6 to 9 and 12 ml/min whereas the mean transit time dropped from 221 to 121 and 108 s, respectively. These results support the assumption that bupivacaine is extensively retained by the pulmonary tissue and that elimination of bupivacaine by metabolism can be neglegted for lung. The hemodynamic parameters of bronchiolar perfusion in the artificially perfused lung were determined using two fluorochrome-labeled macromolecular proteins, i.e. fluorescein-isothiocyanate (FITC)- and lissamine-rhodamine-B 200 (RB 200)-labeled globulin. After 10 min of perfusion at a flow rate of 12 ml/min in the closed system an area of 10.8070 of the peribronchiolar tissue area contained the dye-label FITC. A very similar index (10.1%) of dye-coloured capillaries was obtained when the lungs of anaesthetized rats were examined 10 min after intravenous injection of the fluorochrome into the pulmonary artery in vivo. In isolated perfused rat lungs receiving both FITC and RB 200 59.5% of FITC-labeled capillaries were reached by the second fluorochrome within 2 s. This fraction accounted for 93.3% after 10 s of circulation time. This proves that isolated rat lungs were well perfused in vitro.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1994), S. 99-106 
    ISSN: 1432-1912
    Keywords: Key words Lung perfusion ; Bupivacaine ; Fluorochrome-labeled capillaries ; First-pass retention ; Inulin ; Tritium-labeled water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of rat lung to remove the local anaesthetic drug bupivacaine from the blood was studied in isolated organs which were perfused either in an open (single-pass mode) or in a closed system (recirculating medium). Isolated perfused rat lungs exhibited a very low capacity to metabolize bupivacaine within 3 h during which the drug circulated continuously through the organ. The clearance values differed only by 0.2 ml/min from the control parameters in sham perfusions. The calculated extraction ratio was 0.2% and the elimination half-life was about 210 min. The volume of distribution of bupivacaine was 133 ml which remarkably surmounted the reference values obtained for sham perfusions. The distribution of bupivacaine into the pulmonary tissue was investigated applying the multiple indicator dilution technique to isolated lungs perfused in the single-pass mode. The mean elimination time of model compounds for distribution into the intravascular space, 14C-inulin, and the total water space, 3H-water, were 68 and 75 s at a flow rate of 6 ml/min. The volume of distribution was 5.9 ml for inulin and 6.5 ml for water. The mean transit time for concomitantly injected bupivacaine was 221 s and the volume of distribution was 14.4 ml. The respective parameters of sham perfusions performed without an isolated organ were substantially lower, i.e. mean elimination time 50, 50 and 61 s and distribution volume 4.9, 5.0 and 6.1 ml for inulin, water and bupivacaine. The volume of distribution during single-pass contact of bupivacaine to lung was not substantially influenced by an increase of the flow rate from 6 to 9 and 12 ml/min whereas the mean transit time dropped from 221 to 121 and 108 s, respectively. These results support the assumption that bupivacaine is extensively retained by the pulmonary tissue and that elimination of bupivacaine by metabolism can be neglegted for lung. The hemodynamic parameters of bronchiolar perfusion in the artificially perfused lung were determined using two fluorochrome-labeled macromolecular proteins, i.e. fluorescein-isothiocyanate (FITC)- and lissamine-rhodamine-B 200 (RB 200)-labeled globulin. After 10 min of perfusion at a flow rate of 12 ml/min in the closed system an area of 10.8% of the peribronchiolar tissue area contained the dye-label FITC. A very similar index (10.1%) of dye-coloured capillaries was obtained when the lungs of anaesthetized rats were examined 10 min after intravenous injection of the fluorochrome into the pulmonary artery in vivo. In isolated perfused rat lungs receiving both FITC and RB 200 59.5% of FITC-labeled capillaries were reached by the second fluorochrome within 2 s. This fraction accounted for 93.3% after 10 s of circulation time. This proves that isolated rat lungs were well perfused in vitro.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 70 (1975), S. 401-405 
    ISSN: 1435-1803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine Methode wird beschrieben, die eine Zählung und Kartographierung nichtradioaktiv markierter Mikrosphären in transparenten, dicken Gewebeschnitten ermöglicht. Das Verfahren ist einfach, es erlaubt den direkten Nachweis der Mikrosphären im Gewebe und dadurch eine Aussage über lokale Durchblutungsverhältnisse in normal durchbluteten oder auch künstlich perfundierten Organen.
    Notes: Abstract A method allowing the counting and mapping of non-radioactive microspheres in cleared thick tissue slides is described. The procedure is simple and enables a direct demonstration of the microspheres in the tissue and the resulting evaluation of local blood supply to normally and also artificially perfused organs.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 75 (1980), S. 526-536 
    ISSN: 1435-1803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In Versuchen an der Ratte wurde die funktionelle Kapillardichte in subendokardialen und subepikardialen Anteilen des Herzens unter Ruhebedingungen und unter Stimulation durch Isoprenalin (5,0 μg/kg×min i.v., 3 min) bestimmt. Zur Erfassung der Zahl der perfundierten Kapillaren wurde ein Fluoreszenzfarbstoff (Thioflavin S) in den linken Vorhof infundiert und 1, 3, 5 bzw. 10 s nach Beginn der Infusion das herz exzidiert und schnell kältefixiert. In histologischen Schnitten ließen sich dann diejenigen Kapillaren erkennen und auszählen, die während der Farbstoffinfusion perfundiert worden waren. In beiden Schichten des Myokards wurde mit Verlängerung der Farbstoffexpositionszeit eine Zunahme der Zahl markierter Gefäße beobachtet. Dieser Effekt war in der Isoprenalin-behandelten Gruppe wesentlich geringer und war am deutlichsten in der subendokardialen Schicht ausgeprägt (3560±199 Kap./mm2 Kontrolle, 2190±30 Kap./mm2 unter Isoprenalin-Behandlung, jeweils nach 10 s Farbstoffexposition). Bei der hier verwandten Isoprenalin-Dosis kam es zum Anstieg der Gesamtkoronardurchblutung (3,7±0,6 Kontrolle, 6,8±0,7 Isoprenalin-Behandlung, ml/min×g). Gleichzeitig fand sich eine Reduzierung des relativen Anteils der Subendokard-durchblutung (Verhältnis von subendokardialem zu subepikardialem Fluß 1,08±0,13 unter Kontrollbedingungen, 0,66±0,01 unter Isoprenalin-Behandlung). Die Ergebnisse sprechen dafür, daß die unter Isoprenalin beobachteten Verminderungen der relativen Subendokarddurchblutung nicht auf eine Erschöpfung der myokardialen Kapillarreserve zurückgehen, sondern vermutlich überwiegend durch die Erniedrigung des Perfusionsdruckes bei gleichzeitig erhöhter extravaskulärer Kompression bedingt sind.
    Notes: Summary The functional capillary density in subepicardial and subendocardial layers of rat heart was measured during rest and during isoprenaline-induced (5.0 μg×kg−1×min−1, i.v. over 3 minutes) cardiac stimulation. For determination of the number of perfused capillaries, a fluorescent dye (thioflavine S) was infused into the left atrium; 1, 3, 5 and 10 sec, respectively, after starting dye application, hearts were excised and rapidly cooled down to −50°C. In histological sections capillaries which had been perfused during the dye infusion could be identified and counted. An increase in the number of stained vessels was found in both layers of the myocardium when the time of dye exposure was prolonged. Under these conditions the rise was much smaller in isoprenaline-treated animals, this effect being most marked in the subendocardial layer (3560±199 cap./mm2, control group; 2190±30 cap./mm2, isoprenaline-treated group; dye exposure 10 sec). Isoprenaline — at the dose used — induced an increase in total blood flow (3.7±0.6 ml×min−1×g−1, control group; 6.8±0.7 ml×min−1×g−1, isoprenaline-treated group), however, with a relatively less pronounced increase in the subendocardial blood flow (subendocardial/subepicardial flows: 1.08±0.13, control group; 0.66±0.01, isoprenaline-treated group). These results favour the view that isoprenaline-induced relative reduction in the subendocardial blood flow is due to disturbance of perfusion pressure and extravascular compression rather than to exhaustion of the myocardial capillary reserve.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 80 (1985), S. 661-669 
    ISSN: 1435-1803
    Keywords: coronary blood flow ; coronary vascular resistance ; adenosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The minimal coronary vascular resistance was measured in anesthetized rats. For determination of coronary flow a tube system was inserted which directed the blood from the left carotid artery via the right carotid artery into the ostium of the left or the right coronary artery. A drop chamber in the shunt system enabled flow measurement. Maximal vasodilatation was induced by intra-arterial infusion of adenosine. In non-thoracotomized rats vascular resistance decreased to 20.6% and 20.3% of control values in the left and right coronary artery, respectively (23.8 to 4.9 and 18.2 to 3.7 mm Hg·ml−1·min·g). Thoracotomy led to increased control values (29.3 mm Hg·ml−1·min·g, right coronary artery). Minimal resistance in this latter group was nearly as low as in the closed-chest rats (4.8 mm Hg·ml−1·min·g). It can be assumed that the coronary dilator reserve in the rat lies within the same range as that of larger species e.g. dogs.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 72 (1977), S. 11-18 
    ISSN: 1435-1803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die vorliegenden Experimente wurden zur Untersuchung der Frage durchgeführt, ob unter einer Vasodilatation durch intraarteriell zugeführtes Acetylcholin regionale Blutverteilungsunterschiede in der Skelettmuskulatur auftreten. Hierzu wurde in Versuchen an Katzen der Musculus triceps surae beiderseits isoliert. Auf einer Seite erfolgte die intraarterielle Applikation von Acetylcholin (0,5 μg/kg×min), während die Gegenseite als Kontrolle diente. 4 Minuten nach Beginn der Infusion wurden nichtradioaktive Mikrosphären von 15 μ Durchmesser in die Aorta ascendens injiziert. Die Muskulatur wurde anschließend in 1,0 mm dicke Gefrierschnitte zerlegt und mit Lauge und Glycerin zur Transparenz aufgehellt. In repräsentativen Schnittebenen wurde die Zahl der Mikrosphären pro mm3 ausgezählt. Mit diesem Verfahren wurden auf der mit Acetylcholin behandelten Seite eine relativ höhere Mikrosphärenkonzentration in den proximalen gegenüber den distalen Schnittebenen beobachtet. Ebenfalls unterschiedlich war die Konzentration in den Segmenten. Hier wurden in zentral gelegenen Abschnitten höhere Werte als in Segmenten der Randzonen festgestellt. Auf der Kontrollseite wurden ebenfalls Veränderungen in gleicher Richtung beobachtet, die Unterschiede waren jedoch geringer als in den mit Acetylcholin behandelten Muskeln. Es wird vermutet, daß diese Zeichen einer verstärkten Inhomogenität der regionalen Durchblutung unter der Vasodilatation mit den in der Literatur beschriebenen Hinweisen auf eine Änderung der nutritiven Gewebsdurchblutung durch Acetylcholin in Zusammenhang stehen.
    Notes: Summary The present experiments were performed to study the question whether intraarterially infused acetylcholine changes the local tissue perfusion of the skeletal muscle. In experiments on cats the triceps surae muscles were isolated. While acetylcholine (0.5 μg/kg×min) was infused intraarterially on one side, the opposite side was taken as control. 4 minutes after the start of the infusion non-radioactive microspheres of 15 μm diameter were injected into the ascending aorta. Subsequently the muscles were freeze-sectioned into 1.0 mm thick slices and cleared by sodium hydroxide and glycerine. The concentration of microspheres per mm3 was measured in representative cross sections of the muscle. Higher concentrations of microspheres were observed in the proximal than in the distal slices of the acetylcholine-treated side. The distribution of microspheres was found to be different in the segments as well: higher values were found in the central than in peripheral segments. The untreated side showed a qualitatively similar state. The differences in the distribution pattern, however, were smaller than in the acetylcholine-treated muscles. It is concluded that the increased inhomogeneity of the regional perfusion observed in this study during vasodilation corresponds to results reporting a changed nutritive tissue perfusion during an acetylcholine treatment.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 78 (1983), S. 113-123 
    ISSN: 1435-1803
    Keywords: carbocromene ; cardiac microcirculation ; myocardial capillary density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In Urethan-narkotisierten, thorakotomierten Ratten wurde untersucht, ob die Dichte plasmaperfundierter Kapillaren im Herzen unter einer pharmakologisch ausgelösten Vasodilatation ansteigt. Carbocromen führte in einer Dosis von 3,0 mg/(kg×min) i.v., über 5 min infundiert, zu einem Anstieg der Koronardurchblutung von 6,2±0,6 auf 15,6±0,1 ml/(min×g); Herzfrequenz und Blutdruck waren hierbei nur geringfügig verändert. Die Kapillardichte wurde bestimmt, indem ein plasmamarkierender Farbstoff (FITC bzw. RB 200 an γ-Globulin gekoppelt) für unterschiedlich lange Zeiten demselben Versuchstier infundiert wurde. Bei einer Farbstoff-Applikationszeit von 10 min ergaben sich keine signifikanten Unterschiede in der Kapillardichte Carbocromen-behandelter Tiere im Vergleich zu den Kontrollen (Carbocromen-behandelte Ratten: 3630±90 Kap./mm2 Subepikard. 3360±70 Kap./mm2 Subendokard; Kontrolle: 3750±140 Kap./mm2 Subepikard, 3210±90 Kap./mm2 Subendokard). In den mit dem Vasodilatator behandelten Tieren fand sich bereits nach 1 s eine nahezu vollständige Markierung des Kapillarsystems (3500±170 Kap./mm2 Subepikard, 3070±110 Kap./mm2 Subendokard), während signifikant niedrigere Werte bei einer entsprechenden Markierungszeit in den Kontrollversuchen beobachtet wurden (2560±460 Kap./mm2 Subepikard, 1960±400 Kap./mm2 Subendokard). Die Ergebnisse zeigen, daß die Füllung der kardialen Mikrozirkulation unter der pharmakologisch ausgelösten Vasodilatation beschleunigt erfolgt, daß aber die maximale Dichte plasmadurchströmter Kapillaren nicht ansteigt.
    Notes: Summary Urethane-anesthetized thoracotomized rats were used to ascertain whether the density of plasma-perfused capillaries increases in the heart during pharmacologically induced vasodilation. Carbocromene, in a dose of 3.0 mg/(kg×min) i.v., infused for 5 min, raised coronary blood flow from 6.2±0.6 to 15.6±0.1 ml/(min×g); heart rate and blood pressure were only slightly changed. Capillary density was determined by timed infusions of a plasma label (FITC or RB 200 coupled with γ-globulin), infused for different periods of time in the same animal. No significant difference could be observed in the number of capillaries marked for 10 min in the carbocromene-treated rats as compared to the controls (carbocromene-treated rats: 3,630±90 cap/mm2 subepicardium, 3,360±70 cap/mm2 subendocardium; controls: 3,750±140 cap/mm2 subepicardium, 3,210±90 cap/mm2 subendocardium). In those rats treated with the vasodilator the filling of the microcirculatory system was nearly complete within a labelling period of 1 sec (3,500±170 cap/mm2 subepicardium, 3,070±110 cap/mm2 subendocardium), whereas significantly lower values were found when the dye was infused for 1 sec in the controls (2,560±460 cap/mm2 subepicardium, 1,960±400 cap/mm2 subendocardium). The results indicate that the filling of the cardiac microcirculatory system is accelerated by a pharmacologically induced vasodilation, the maximal density of plasma-perfused capillaries is not raised, however.
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