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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European biophysics journal 11 (1985), S. 259-263 
    ISSN: 1432-1017
    Keywords: K+-channels ; patch-clamp ; heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Studies on single K+-channel currents recorded from isolated rat heart muscle cells, in which early repolarization is known to be exceptionally fast, are reported here. A K+-channel which is blocked by TEA (tetraethylammonium) from the inside only has been found. The total open time of the channel, measured in steady-state after activation, indicated outward rectifying properties. The single channel conductance increases with depolarization from 25 pS at-70 mV to 75 pS at+70 mV. Selectivity of the channel has also been measured and it was found that only Rb+ and K+ can permeate the channel, whereas the permeability (P) for Li+, Na+, Cl-, Mg2+, and Ca2+ is less than 0.05 times $${\text{P}}_{{\text{K}}^{\text{ + }} } $$ . Ba2+ and Cs+ block the channel activity. These results clearly demonstrate the existence of K+-selective outward rectifying conductance pathways in rat ventricular myocytes.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 154 (1988), S. 236-244 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 400 (1984), S. 197-199 
    ISSN: 1432-2013
    Keywords: rat heart ; enzymatically isolated ventricular myocytes ; membrane potential ; microelectrodes ; suction pipettes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Single myocytes from adult rat hearts were prepared following the method of Powell and co-workers (9, 10, 11). Low resting potentials (Em) could be improved by three techniques. (i) Elevation of Cao to 7.2 mM which, however, mostly resulted in spontaneity and irreversible contracture. (ii) Pre-incubation in a “KB medium” (6). (iii) Use of suction pipettes instead of tapered microelectrodes for intracellular recordings (2). It is concluded that low Em measured previously (11) were due to membrane damage upon microelectrode impalement accopanied by insfufficient healing of the membrane around the electrode insertion.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 465-476 
    ISSN: 1432-1440
    Keywords: Myocardial ischemia ; Reperfusion injury ; Oxygen paradox ; Contracture ; Calcium ; Oxygen radicals ; ATP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After prolonged ischemia or hypoxia myocardial injury is not reversed but exacerbated by a resupply of the tissue with oxygen and substrates. The mechanism by which reversible ischemic or hypoxic myocardial injury becomes irreversible is not yet understood. It has been debated whether “reperfusion injury” merely uncovers pre-existing irreversible injury, or is indeed caused by the reperfusion/reoxygenation process. In recent years, three theories have been discussed that relate the onset of irreversibility either to: a critical energy loss; a critical accumulation of cellular calcium; or to the deleterious effects of free radical formation. In certain experimental models for each of these theories favourable results have been obtained. Current research suggests that absolute reversibility thresholds in energy depletion or calcium accumulation in the ischemic or hypoxic cell do not exist. A key role of free radical injury for reperfusion injury must also be questioned. There is, however, evidence that in tissue reversibility of ischemic cardiomyocyte injury is limited by conditions that make calcium-induced hypercontracture upon reoxygenation unavoidable. This occurs when, by hypercontracture, mutual mechanical disruption of the cells destroys the tissue. From isolated cardiomyocytes that are able to metabolically survive hypercontracture it has been observed that these metabolic conditions do not represent the last biological possibility to reverse injury.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 80 (1993), S. 132-134 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2013
    Keywords: Anoxia ; adult cardiomyocytes ; creatine kinase ; free energy change ; ATP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In isolated cardiomyocytes from adult rat heart the free energy change of ATP hydrolysis (dG) was determined under conditions of substrate-free anoxia. Changes of free cytosolic ADP concentrations, needed for the calculation of dG, were determined by two indirect methods since a direct measurement is not feasible: (i) via the mass action ratio of the creatine kinase reaction (CK) assuming near equilibrium conditions, and (ii) via quantification of the net hydrolysis of ATP to ADP by a detailed balancing of possible contribution to Pi production. Both approaches gave virtually identical results, showing that in anoxia only 6% of the ATP hydrolysed are hydrolysed to ADP and 94% completely to adenosine and further degradation products. The convergence of both methods also indicates that in this model the CK reaction is indeed catalysed near its equilibrium. Therefore estimations of free ADP and dG using its mass action ratio are valid. In anoxic cardiomyocytes dG values fell from 57 kJ/mol in normoxia to 42 kJ/mol after 120 min anoxia, corresponding to a decrease of ATP contents from 24 to 4 nmol/mg protein.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2013
    Keywords: Key words Free radicals ; Ischaemia ; Reperfusion ; Myocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study addressed the question of whether the sarcolemmal fragility of cardiomyocytes after anoxia and subsequent reoxygenation can be altered by modulation of the cellular glutathione state. Isolated ventricular cardiomyocytes (from adult rats) were exposed to 120 min anoxia and subsequently to 30 min reoxygenation. Osmotic stress was generated by reduction of medium osmolarity from 270 to 80 mosmol/l and sarcolemmal fragility assessed by the leakage of lactate dehydrogenase (LDH). Under normoxic conditions 6.7±1.0 % of total LDH activity was found extracellularly. Hyposmolar reoxygenation, but not hypoosmolar anoxia, increased LDH release (17.9±2.7% of total, P〈0.05). Increasing cellular glutathione content by pretreatment with N-acetylcysteine (1 mM) reduced LDH release following hyposmolar reoxygenation (12.3±1.9% vs. 18.2±2.9% of LDH in medium, P〈0.05). Depletion of glutathione content by pretreatment with buthionine sulphoximine (BSO, 200 µM), increased LDH release following osmotic stress already in normoxia (10.5±1.8% of LDH in medium; P〈0.05 vs. no BSO), and even further after reoxygenation (21.8±3.2%, P〈0.05 vs. normoxia). We conclude that the increased sarcolemmal fragility in reoxygenated cardiomyocytes is due to reoxygenation in the presence of reduced antioxidant defence.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2013
    Keywords: Cardiac anoxia ; Enzyme release ; Reoxygenation damage ; Mitochondrial swelling ; Contracture development ; Cell lysis ; Adult heart cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cultured adult cardiac myocytes were exposed to anoxia under substrate-free conditions and then reoxygenated. When comparing the oxygen deficient organ to the anoxic cell culture, we see that metabolic changes in the latter system proceed in a similar, yet prolonged manner, as in arrested hearts. Release of cytosolic enzymes starts with minor energetic disturbances and proceeds closely correlated to the actual ATP level. Below 2 μmol ATP/gww, an increasing number of cells becomes irreversibly damaged, above this level, 30 min reoxygenation leads to extensive recovery of the whole preparation. The results indicate that leakage of cytosolic enzymes during the early stage of anoxia is due to a gradual protein release from the individual cells and is related to reversible membrane alterations. Reoxygenation does not induce changes considered typical of the ‘oxygen paradox’. Since mechanical cell-cell interactions are absent in this model, it is suggested that aggravation of tissue damage in heart tissue reoxygenated late is mainly caused by mechanical forces.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 91 (1996), S. 191-202 
    ISSN: 1435-1803
    Keywords: Acidosis ; calcium ; hypercontracture ; reperfusion injury ; Na+/HCO3 − ; symporter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In ischemia the cytosol of cardiomyocytes acidifies; this is reversed upon reperfusion. One of the major pHi-regulating transport systems involved is the Na+/H+ exchanger. Inhibitors of the Na+/H+ exchanger have been found to more effectively protect ischemic-reperfused myocardium when administered before and during ischemia than during reperfusion alone. It has been hypothesized that the protection provided by pre-ischemic administration is due to a reduction in Na+ and secondary Ca2+ influx. Under reperfusion conditions Na+/H+ exchange inhibition also seems protective since it prolongs intracellular acidosis which can prevent hypercontracture. In detail, however, the mechanisms by which Na+/H+ exchange inhibition provides protection in ischemic-reperfused myocardium are still not fully identified.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1435-1803
    Keywords: respiratory quotient ; working rat heart ; substrate utilization ; oxygen demand ; oxygen consumption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurde eine Methode entwickelt, um an einem isolierten, arbeitenden Rattenherzen kontinuierlich den RQ sowie das Verhältnis aus O2-Verbrauch und O2-Bedarf (EQ) zu registrieren. Aus dem aktuellen RQ können Aussagen über die aktuell oxidierten Substrate gemacht werden; der EQ ist im Steady-state ein Maß für den ATP/O-Quotienten der oxidierten Substrate, außerdem kann damit eine vorübergehende O2-Schuld erfaßt werden. Für die RQ-Messung wird die O2-AVD und die CO2-Freisetzung gemessen. Da bei Verwendung eines bikarbonathaltigen Perfusionsmediums die CO2-AVD nur sehr gering gegenüber der arteriellen CO2-und Bikarbonatkonzentration ist, wird ein bikarbonatfreies Perfusat verwendet. Im Koronareffluat wird nach Absenken des pH-Wertes auf ca. 4, um das CO2/HCO 3 t- -Gleichgewicht auf die Seite des gelösten CO2 zu verlagern, der CO2-Partialdruck gemessen. Weiterhin wird fortlaufend der Ventrikeldruck, das HZV sowie der Koronarfluß registriert. Alle Meßdaten werden über einen AD-Converter in einen LSI11-Computer eingelesen. Daraus werden Herzfrequenz, max. Ventrikeldruck, dP/dtmax, O2-Verbrauch, O2-Bedarf nach Bretschneider, der RQ und der EQ errechnet. An zwei Beispielen wird dargestellt, daß dieses Modell für physiologische, metabolische und pharmakologische Untersuchungen gut geeignet ist.
    Notes: Summary A method was developed for continuous monitoring of the respiratory quotient (RQ) and the ratio of O2-consumption to O2-demand (EQ) in an isolated working rat heart preparation. The RQ allows to get informations about substrates actually oxidized in the myocardium. The EQ is a parameter which behaves reciprocally to the ATP/O of the oxidized substrates during steady state and additionally it allows monitoring of a transitory oxygen debt. For registration of RQ the arterio-venous O2-difference and the CO2-release are measured. As the CO2-production is very small compared with arterial CO2- and HCO 3 − -concentrations when using a bicarbonate buffer for perfusion, a bicarbonate-free perfusion-fluid is used. In a portion of coronary effluent the pH is lowered to shift the CO2/HCO 3 − -equilibrium to the side of dissolved CO2. Then the pCO2 is measured with a CO2-Nelectrode. Additionally, ventricular pressure, cardiac input and coronary flow are continuously registrated. All data are fed via an AD-converter into an LSI 11-computer. Heart rate, maximum ventricular pressure, dP/dtmax, oxygen demand after Bretschneider's formula, RQ and EQ are calculated. The advantages of the system described are demonstrated with two examples.
    Type of Medium: Electronic Resource
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