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  • 1
    ISSN: 1432-1440
    Keywords: Coronary occlusion ; epicardial mapping ; infarction size ; fibrinolysis ; Streptokinase ; fibrinogen degradation products ; Coronarocclusion ; epicardiales EKG ; Infarktgröße ; Fibrinolyse ; Streptokinase ; Fibrinogen-Spaltprodukte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 17 narkotisierten Hunden wurden mehrere Seitenäste des Ramus descendens der linken Kranzarterie unterbunden. Die ST-Segmentelevation im epikardial abgeleiteten EKG stieg dabei bis auf 22 mV nach 5 min und 19 mV nach 20 min an. Aortendruck, enddiastolischer Druck im linken Ventrikel, Herzfrequenz und die hämostasiologischen Parameter (Plasmathrombinzeit, Thrombinkoagulasezeit, Reptilasezeit, Plasmafibrinogen, Staphylokokken-Clumping-Test) änderten sich nicht. 20 min nach Beginn der Okklusion wurden die Gefäße geöffnet. Nachdem sich die St-Segmenthebung zurückgebildet hatte, wurde eine kontrollierte Fibrinolyse (Streptokinase 1,5 Mega I.E. in 30 min initial, Fortführung mit 0,75 Mega I.E./h) eingeleitet. Wenn die hämostasiologischen Parameter eine effektive Lyse anzeigten, wurden die gleichen Gefäße erneut unterbunden. Auch jetzt änderten sich die hämodynamischen Größen nicht wesentlich. Die ST-Segment-Elevation war jedoch signifikant um 50% geringer als nach einfacher Ligatur. Eine Kontrollgruppe, die nur das Lösungsmittel der Streptokinase erhielt, zeigte dagegen einen unveränderten Anstieg der ST-Streckenelevation. Die Wirkung der Streptokinase wird auf das Auftreten von Fibrinogen-Spaltprodukten und die Senkung des Fibrinogenspiegels zurückgeführt, die eine Verbesserung der Mikrozirkulation hervorrufen.
    Notes: Summary In 17 unaesthetized dogs several side branches of the left descending coronary artery were ligated. The ST-segment elevation in the epicardial ECG ascended to 22 mV after 5 min and to 19 mV after 20 min. Aortic pressure, left ventricular enddiastolic pressure, heart rate and hemostasiological parameters (thrombin-time, thrombin-coagulase-time, reptilase-time, plasma-fibrinogen, staphylococcal clumping test) did not change significantly. 20 min after the beginning of coronary occlusion, the vessels were reopened. When ST-segment elevation had disappeared, a controlled fibrinolytic therapy (Streptokinase 1.5 Mega I.E. in 30 min, later on 0.75 Mega I.E./h) was induced. When an effective fibrinolysis could be demonstrated by the hemostasiological parameters, the same vessels were occluded again. Now the hemodynamic parameters too did not change significantly, but the ST-segment elevation was significantly diminished for more than 50% compared with simple ligation. A control group, which only got the solvent of the streptokinase, showed the same ST-segment elevation. This effect, induced by streptokinase is ascribed to fibrinogen degradation products and a diminution in the amount of fibrinogen which cause an improvement of microcirculation.
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  • 2
    ISSN: 1046-5928
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0167-4781
    Keywords: DNA recognition ; Modified oligonucleotide ; Protein-nucleic acid interaction ; Restriction enzyme ; Site-directed mutagenesis
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 314 (1970), S. 14-26 
    ISSN: 1432-2013
    Keywords: Isolated Vascular Smooth Muscle ; Contractility ; pH ; Norepinephrine ; Dose-Response-Curve ; Basic Tension ; Isolierter Gefäßmuskel ; Contractilität ; pH ; Noradrenalinwirkung ; Dosis-Wirkungskurven ; Basaltonus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An isolierten Spiralstreifen der Rattenaorta (37°C, 2000 mg Vorspannung) wurde der Einfluß einer Variation der extracellulären H+-Konzentration (pH e ) zwischen pH e 7,3–5,9 auf die durch Noradrenalin (NA) induzierte Kontraktionsamplitude untersucht. 1. Eine pH e -Veränderung in diesem Bereich besaß keine beständige Wirkung auf die passive Spannung des Präparates. Kurzfristig auftretende Kontrakturen bildeten sich 8–10 min nach pH-Senkung vollständig zurück (Abb. 1b). 2. Bei erniedrigtem pH e war die Spannungsentwicklung des Gefäßpräparates auf maximal wirksame NA-Testreize (3·10−6 g NA/ml) signifikant und reversibel vermindert (Abb. 1 und 2, Tabelle). 3. Eine Senkung von pH e in Stufen während der adrenerg bedingten Kontraktion veränderte in gleicher Weise reversibel die Präparatspannung (Abb. 3 und 4, Tabelle). 4. Die Dosis-Wirkungskurve (DWK) von NA zeigte bei erniedrigtem pH e einen verzögerten Anstieg und eine Linksverlagerung des Gipfels (von 3·10−6 bei pH e 7,3 auf 1,5·10−6 g NA/ml bei pH e 6,4). Die Minderung der Contractilität (Tabelle) war im niedrigen Dosisbereich noch ausgeprägter als bei der maximal wirksamen NA-Konzentration (Abb.7). 5. Die Spannungsentwicklung auf eine maximal wirksame NA-Menge nahm in allen drei Versuchsreihen bei Steigerung der extracellulären H+-Konzentration linear ab und erreichte (Angaben als $$\bar x \pm s_{\bar x} $$ in Prozent der Kontrollwerte bei pH 7,3) 87,32±1,71% bei pH e 6,40 und 51,30±3,63% bei pH e 5,90. Eine Extrapolation der aus dem Spannungsabfall errchneten linearen Beziehung zwischen H+-Konzentration und Contractilität würde die vollständige Unterdrückung der durch NA-bedingten Kontraktion des Gefäßmuskelstreifens bei pH e 5,6 ergeben (Abb. 5). 6. Da die Kontraktionsamplitude des Gefäßstreifens bei Inkubation des Präparates in pufferfreier Lösung nach 6 min 113,47±6,49%, nach 30 min 93,92±5,54% der Kontrollwerte betrug, kann die Contractilitätsminderung bei Senkung des pH e nicht auf eine Verminderung des extracellulären Pufferbestandes zurückgeführt werden. 7. Die Beziehungen zwischen extracellulärer H+-Konzentration, fester gebundener Ca-Fraktion, intracellulärem pH-Wert und dem Kontraktionsprozeß werden diskutiert.
    Notes: Summary The influence of the extracellular hydrogen ion concentration, varied within the range of pH 7.3 and 5.9, on the norepinephrine-induced contraction of isolated helical strips of rat aorta (37°C, 2000 mg basic tension) was studied. 1. Within the investigated range there was no constant effect of pH variation on the passive basic tension of the strip. Transitory contractures disappeared 8 to 10 minutes after pH depression (Fig. 1b). 2. The active tension of the vascular strip, induced by norepinephrine (NE) (3×10−6 g/ml) during different pH values of bath solution, was reversibly diminished by increasing the extracellular H+-concentration (Figs. 1 and 2, Table). 3. Stepwise augmentation of the extracellular H+-concentration during adrenergic-induced contraction diminished also the tension of the strip reversibly (Figs. 3 and 4, Table). 4. A diminution of the pH of bath solution caused a retarded increase of the dose-response-curve of NE, shifted the peak of the curve to the left (from 3 to 1.5×10−6 g NE/ml at pH 6.4), and diminished the maximum of the tension developed (Figs. 6 and 7, Table). This corresponds to a more pronounced decrease of contractility at small NE-concentrations. 5. There was a linear function between the tension developed under maximal effective NE-concentration and augmentation of extracellular H+-concentration (Figs. 2 and 4) in all 3 experimental groups. Compared with the control value (100% at pH 7.3) this function became 87.37±1.71% at pH 6.4 and 51.30±3.63% at pH 5.9 (Table). An extrapolation would give the complete suppression of the NE-induced contraction of vascular smooth muscle strip at pH 5.6 (Fig. 5). 6. The amplitude of contraction of the vascular strip after 6 minutes of incubation in a buffer-free medium was 113.47±6.49%, after 30 minutes 93.92±5.54% of the control-values. Therefore, the diminution of the contractility after increasing the extracellular hydrogen ion concentration is not caused by a diminution of the extracellular buffer. 7. The correlations between extracellular H+-concentration, tightly bound calcium-fraction, intracellular pH, and process of contraction are discussed.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 387-400 
    ISSN: 1432-1912
    Keywords: Myocardial Infarction ; Coronary Blood Flow ; Epicardial Mapping ; Nitroglycerin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of nitroglycerin (N.G.) on the size of myocardial infarction was studied in 12 open-chest dogs with chloralose-urethane anesthesia by means of epicardial ECG-mapping and compared with the influence of simple ligature of the same coronary artery branch. In order to identify the specific effect of N.G. on the heart and the coronary circulation without contribution of the peripheral circulation in 6 dogs aortic pressure was stabilized by a clamp placed around the descending aorta and heart rate was kept constant by atrial pacing. Nitroglycerin (0.5 mg/kg i.v.) infused during the occlusion period of 20 min resulted in a decrease of mean arterial pressure for 27 mm Hg (p〈0.005) and left ventricular enddiastolic pressure for 2 mm Hg (p〈0.05) indicating a diminishment in oxygen demand. Mean coronary blood flow was reduced to a similar extent (18%) as in the control infarction (22%). Compared to simple occlusion no significant alteration in the extent of ST-elevation in the epicardial electrogram was observed during N.G.-infusion even in the presence of hypotension. In the stabilized group with constant afterload (mean arterial pressure) and heart rate nitroglycerin induced a slight, but not significant decrease of the enddiastolic left ventricular pressure compared to the control group. However, coronary blood flow and ST-elevation were unaffected. Thus, neither in the unstabilized nor in the stabilized group the extent of myocardial injury after ligature of a coronary artery branch were influenced by nitroglycerin. Obviously the improvement in the oxygen demand during nitroglycerin is out balanced by the reduction in oxygen supply so that in effect myocardial infarction size is not altered by N.G. as estimated from epicardial ECG.
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  • 6
    ISSN: 1432-1912
    Keywords: Vascular Smooth Muscle ; Adrenergic Alpha-Receptors ; Vasopressin ; Potassium Depolarization ; Noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Determinations of the maximum tension development of the helical strip of rat aorta showed that the maximal response to vasopressin amounted to 75% and that to potassium-induced depolarization to 93% of the contraction caused by noradrenaline (=100%). 2. When phentolamine (1.2-6.2×10−6 g/ml) was added to the bath 15 min before the determination of dose-response curves for noradrenaline, there was a concentration-dependent shift of the curve to the right; the slope of the curve, the ED50 and the concentration of noradrenaline required for maximum activation of the muscle increased. However, when phentolamine (1.2 to 6.2×10−6 g/ml) was administered after the development of a maximum response to noradrenaline, the muscle relaxed nearly completely. In the presence of phenoxybenzamine (3×10−6 g/ml) noradrenaline failed to cause contractions. 3. The dose-response curve for vasopressin was sigmoid. The presence of phentolamine did not affect the ED50 (at 1.6×10−3 IU/ml) or the peak of the curve (at 1.2×10−2 IU/ml). The administration of vasopressin to depolarized muscles always caused a contractile response. When the muscle was activated repeatedly by vasopressin, tachyphylaxis occurred. 4. Block of the adrenergic alpha-receptors influenced the contractile response to depolarization far less than that to noradrenaline. 5. In accordance with earlier studies, the present results lead to the conclusion that the contraction of the vascular smooth muscle in response to noradrenaline, vasopressin, or depolarization, respectively, involves different mechanisms.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 320 (1970), S. 133-141 
    ISSN: 1432-2013
    Keywords: Vascular Smooth Muscle ; Norepinephrine ; Potassium ; Membrane Potential ; Gefäßmuskulatur ; Noradrenalin ; Kalium ; Membranpotential
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Zwischen der extracellulären K-Konzentration und der durch sie induzierten Spannung des isolierten Gefäßmuskelstreifens der Rattenaorta besteht im Bereich von 4,8–131,8 mM K/l eine S-förmige Beziehung (Abb.4). 2. Der Gipfel der Kontraktur liegt bei 131,8 mM K/l und beträgt 101,3% der Stärke eines optimal wirksamen Noradrenalin (=NA)-Testreizes (3·10−6 g NA/ml) bei normalem K-Spiegel (Abb.4). Die Spannung steigt nach maximaler Aktivierung durch K signifikant schneller an als nach einem gleich stark wirkenden NA-Reiz. 3. Die adrenerg ausgelöste Kontraktionsamplitude wird mit zunehmender extracellulärer K-Konzentration vermindert (Abb.1) und beträgt bei 131,8 mM K/l noch 21,5% der Kontrollwerte (Abb.2). 4. Die durch die K-Kontraktur und anschließende NA-Gabe insgesamt induzierte Spannung bleibt bis 20 mM K/l relativ konstant und steigt bei weiterer Erhöhung des extracellulären K-Spiegels bis auf maximal 131,8% an (Abb.4). 5. Diese Befunde sprechen gegen eine NA-Wirkung ausschließlich über das Membranpotential. K und NA führen offenbar über unterschiedliche Mechanismen zur Aktivierung der Gefäßmuskulatur.
    Notes: Summary 1. Between extracellular potassium concentration (4.8–131.8 mEq K/l) and potassium-induced tension a S-like function of the isolated strip of rat aorta has been found (Fig.4). 2. The peak of the potassium-induced tension was placed at 131.8 mEq K/l and thus amounted to 101.3% of the value of the maximum adrenergic contraction at normal potassium level (Fig.4). The tension development after potassium-induced activation occurred significantly faster than that after norepinephrine. 3. The amplitude of the adrenergic-induced contraction decreased with increasing potassium concentration (Fig.1) and reached 21.5% at 131.8 mEq K/l (Fig.2). 4. When the vascular smooth muscle was activated by norepinephrine (3×10−6 g/ml) after application of potassium (Figs.1 and 3), the total tension was relatively constant up to a potassium concentration of 20 mEq/l and increased to 131.8% by elevation of the extracellular potassium up to 99.7 mEq/l (Fig.4). 5. According to these results the effect of norepinephrine is not mainly concerned with alterations of the membrane potential. From this it seems likely, that potassium and norepinephrine activate the vascular smooth muscle in a different manner.
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  • 8
    ISSN: 1432-2013
    Keywords: Cardiac Performance ; Frequency Potentiation ; Starling Mechanism ; Vagus Nerve Stimulation ; Ventricular Pacing ; Left Ventricular Volume ; dP/dt ; Herzdynamik ; Frequenzinotropie ; Frank-Starling-Mechanismus ; Vagusreiz ; Schrittmacher ; Ventrikelteilvolumina ; dP/dt
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An narkotisierten Hunden mit geschlossenem Thorax wurde die Herzfrequenz zwischen 40 und 130/min variiert. 1. Unter stabilisiertem aortalem Mitteldruck bestand bei einer Variation des Sinusrhythmus durch abgestuften Vagusreiz eine negative, exponentielle Beziehung zwischen Herzfrequenz und enddiastolischem Druck (EDP). Die gleichfalls negativen, jedoch linearen Regressionen von Herzfrequenz und enddiastolischem Volumen (V d), Schlagvolumen (V s) bzw. Austreibungszeit waren in der von uns gewählten Relativdarstellung untereinander praktisch gleich. — Entleerungsquotient (V s/V d) und mittlere systolische Stromstärke (MRE) blieben mit 0,507 bzw. 7,15 ml/kg·sec unabhängig von der Herzfrequenz nahezu konstant. — Die Volumenparameter werden demnach hauptsächlich durch den Frank-Starling Mechanismus bestimmt, wogegen die Frequenzinotropie in der positiv linearen Beziehung zwischen Herzfrequenz unddP/dt max zum Ausdruck kommt. 2. Unter ventrikulärem künstlichem Herzantrieb und stabilisierter Nachbelastung blieben diese Zusammenhänge prinzipiell gleich. Allerdings ergab sich im höheren Frequenzbereich eine deutliche depressive Wirkung des Schrittmachers: bei 114,9/min warenV s und Herzminutenvolumen trotz geringfügig größerer enddiastolischer Füllung um rund 21% kleiner als die Vergleichswerte unter Sinusrhythmus. Damit wurden auchV s/V d und MRE von der Schlagzahl abhängig. 3. Das Absinken des Systemdruckes in der Bradykardie führte stets zu einer signifikanten Verminderung von EDP,V d unddP/dt max. DaV s und Austreibungszeit gleichzeitig vergrößert waren, wurdenV s/Vdund MRE bei unbeeinflußtem Blutdruck unter Sinusrhythmus und künstlichem Schrittmacherantrieb frequenzabhängig.
    Notes: Summary The effect of changes in heart rate between 40 and 130/min on cardiac dynamics was studied in anesthetized dogs with closed chest. 1. At stabilized aortic mean pressure and variation of sinus node rhythm by graduated stimulation of the right vagus nerve there was a negative exponential function between heart rate and enddiastolic pressure (EDP). The likewise negative, but linear regressions between heart rate and enddiastolic volume (V d), or stroke volume (V s), or ejection time, respectively, were almost equal one to another as far as the relative values are concerned. Ejection fraction (V s/V d) and mean rate of ejection (MRE) ranged independently of the heart rate almost constantly at 0.507 or 7.15 ml/kg·sec, respectively. Therefore, the ventricular volumes were primarily determined by the Frank-Starling mechanism, whereas frequency potentiation caused a positive linear regression between heart rate anddP/dt max. 2. When heart rate was increased by right ventricular pacing at stabilized aortic blood pressure, the results obtained were the same in principle. But there was a distinct depressive effect of ventricular pacing at higher heart rates: at 114.9/min, stroke volume and cardiac output became about 21% smaller than under sinus node rhythm, although the enddiastolic filling was insignificantly increased. Therefore,V s/V d and MRE became dependent on heart rate. 3. The diminution of blood pressure at low heart rates always caused a significant reduction of EDP,V d, anddP/dt max. SinceV s and ejection time had been enlarged simultaneously,V s/V d and MRE became dependent on heart rate, when, under sinus node rhythm or artificial pacemaker, blood pressure had not been stabilized.
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  • 9
    ISSN: 1432-2013
    Keywords: Vascular Smooth Muscle ; Mechanisms of Activation ; Noradrenaline ; Potassium-Induced Depolarization ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Contraction of helical strips of the rat aorta was induced by 3 μg/ml of noradrenaline or by potassium-rich solution (80–120 mM K). The resulting amplitudes of contraction were maximal for these respective ways of activation and showed almost the same value in this preparation. 2. The noradrenaline-induced tension, but not the contraction induced by depolarization, decreased, when the hydrogen ion concentration of the bath solution was increased. Furthermore, the response to noradrenaline was more sensitive to a blockade of the adrenergic alpha-receptors or a variation of the bath temperature. 3. Since, after the application of papaverine, the amplitudes of contraction produced by noradrenaline or depolarization were diminished to the same degree, papaverine probably acts on the later steps of the activation-contraction mechanism. 4. When verapamil (iproveratril) was applied in order to inhibit excitationcontraction coupling, tension development after depolarization was influenced to a higher degree than noradrenaline-induced contraction. 5. The fact that it is possible to inhibit the response to depolarization without substantial influence on the response to noradrenaline andvice versa led to the conclusion that in the rat aorta depolarization on the one hand and noradrenaline on the other hand act via different mechanisms of activation.
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  • 10
    ISSN: 1432-2013
    Keywords: Vascular Smooth Muscle ; Norepinephrine ; Potassium-Depolarization ; Temperature ; Calcium ; Gefäßmuskelkontraktion ; Noradrenalin ; Kalium-Depolarisation ; Temperatur ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An isolierten Spiralstreifen der Rattenaorta wurde der Einfluß der Badtemperatur auf die passive Ruhespannung und die maximale, durch Noradrenalin (=NA) bzw. Kalium (=K) induzierte Kontraktionsamplitude untersucht. 1. Zwischen 37°C und 15°C verminderte eine Abkühlung den Basaltonus reversibel um jeweils 20 dyn/°C (Abb.1a-d und 4a). 2. Die adrenerg ausgelöste Kontraktionsamplitude besaß ein Optimum um 37°C, war unter 33,5°C linear zur Temperatur korreliert und bei 15°C nahezu aufgehoben (Abb.3a). In Ca-armer Lösung (1,1 statt 2,4 mM/l) zeigte sich ein signifikant stärkerer Temperatureinfluß (Tab.1). 3. Bei 37°C betrug die zur maximalen adrenergen Aktivierung erforderliche NA-Konzentration 2,4·10−6 g/ml. Sie sank zwischen 37°C und 25°C exponentiell um mehr als eine Zehnerpotenz. 4. Die durch 136 mM/l K erzeugte Spannung zeigte nur eine geringe Temperaturabhängigkeit (Abb.4b). Eine Senkung der Ca-Konzentration blieb dabei ohne signifikanten Einfluß (Tab.1). 5. Bei einem Temperatursprung von 20°C auf 30°C ergab sich für die adrenerge Aktivierung ein Q10 von 2,8 und für die Depolarisation einQ 10 von 1,23. Dieser Befund spricht in Übereinstimmung mit früheren Ergebnissen für eine unterschiedliche Aktivierung der kontraktilen Elemente.
    Notes: Summary In isolated helical strips of rat aorta, the influence of a variation of bath-temperature on the passive tension as well as on the force of contraction, induced by norepinephrine (=NE) or potassium-depolarization respectively, was investigated. 1. Within the range of 37°C and 15°C the passive tension was diminished reversibly by cooling to an extend of 20 dyne/°C (Fig.1a-d, 4a). 2. The NE-induced contraction reached its highest value at 37°C. Between 33.5°C and 15°C the existence of a linear function between temperature and force of contraction could be shown. The contraction was almost abolished at 15°C (Fig.3a). Changing the calcium content of the bath-fluid from 2.4 to 1.1 mM, the slope of the linear regression curve increased significantly (Table 1). 3. At 37°C the concentration of NE, necessary for the maximum force of contraction, was 2.4×10−6 g/ml. The peak of the dose-response-curve shifted to lower NE-concentration by cooling the bath-fluid (Fig.2). From 37°C to 25°C there was an exponential function between temperature and that NE-concentration which induced the highest degree of contraction (Fig.3b); e.g., lowering the temperature by each 3.14°C, this maximum effective NE-concentration was halved. 4. Increasing the potassium concentration to 136 mM, the dependence on temperature of the force of contraction became smaller than after activation by NE (Fig.4b). The influence of a reduction of the calcium concentration was negligible in these experiments (Table 1). 5. Changing the temperature from 20°C to 30°C, there was aQ 10 value of 2.8 for the NE-induced contraction and of 1.23 for the activation by depolarization. 6. According to earlier results, the activation of the vascular smooth muscle by depolarization on the one hand and NE on the other hand is discussed on the basis of suggesting different mechanisms.
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