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Biomedical subjects

W Klaus

Publications and source records attributed to W Klaus.

At least 127 records · Page 7Linked to original sources
PubMed1980

Prostacyclin-induced coronary vasodilation. Interactions with adenosine, cyclic AMP and energy charge in the rat heart in vitro.

The action of prostacyclin (PGI2) on several biochemical and physiological parameters of myocardial function and coronary perfusion was studied in the rat heart in vitro, perfused according to Langendorff either at constant pressure (65 mmm Hg) or at constant volume (8 ml/min). PGI2 dose-dependently decreased coronary vascular resistance, the ED50, being 5--10 nM, whereas that of adenosine was 550--650 nM. PGI2 (30 nM) did not alter the myocardial energy-rich phosphate content but diminished myocardial cAMP by 23% and adenosine release by 61%. In contrast to adenosine, the coronary dilating activity of PGI2 was not inhibited by isobutyl-methyl-xanthine (MIX; 0.4 microM). There were no direct effects of PGI2 on myocardial contractile force, oxygen consumption or heart rate. The results provide evidence for (1) a direct powerful coronary dilating activity of PGI2 which appears to be independent of adenosine, (2) the absence of any direct activity of the compound on myocardial contraction and energy charge.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Differences in the potassium dependence of the myocardial action of some semisynthetic cardiotonic steroids.

Experiments on guinea pig isolated papillary muscle indicated different dependence of the functional actions of cardiac aglycones and some semisynthetic derivatives on the external K+, concentration. Whereas toxicity of the aglycones and their acetates was increased by low K+, that of the "alkylating" compounds remained unchanged; drug-induced contractility was increased uniformly. These differences are explained on the basis of the ATPase reaction scheme, including a carrier-mediated transport of cardiac glycosides.

Animals↗
PubMed1978

Sodium-dependent cardiac glycoside binding: experimental evidence and hypothesis.

1 The influence of increasing Na+ concentrations on the binding of digitoxin, digoxin and ouabain was examined in a Na+-K+-ATPase preparation of guinea-pig hearts. 2 Two distinct processes seem to be involved in this interaction: one binding process was activated at low Na+ concentrations. The maximum binding capacities were different and the K0.5 values were nearly identical for the cardiac glycosides studied. 3 In contrast, the second binding process was activated at appreciably higher Na+ concentrations, the maximum binding capacities were almost identical and the K0.5 values were different for the cardiac glycosides studied. 4 On the basis of these results attempts are made to explain the well known differences in the myocardial accumulation of cardiac glycosides.

Adenosine Triphosphatases↗
PubMed1977

Evidence for two different Na+-dependent [3H]-ouabain binding sites of a Na+-K+-ATPase of guinea-pig hearts.

1. The influence of various Na+ concentrations on [3H]-ouabain binding was studied in experiments on a microsomal Na+-K+-adenosine triphosphatase (ATPase) from guinea-pig hearts. 2. The ATP-independent cardiac glycoside binding was not influenced by increasing Na+ concentrations. However, a good correlation was found between the ATP-dependent [3H]-ouabain binding and Na+ concentration. 3. A more detailed analysis of these results according to Hofstee (1952) revealed two distinct processes involved in this interaction: one ouabain binding process was activated at rather low Na+ concentrations, (K0.5 = 4.5 mM); this type of [3H]-ouabain binding was strongly correlated to the Na+ concentration necessary for half maximum phosphorylation (K0.5 = 1 mM). The other ouabain binding process was predominant at high Na+ concentrations (K0.5 = 69 mM). 4. On the basis of the commonly accepted ATPase reaction cycle a model for the interaction of cardiac glycosides with the Na+-K+-ATPase is proposed, assuming two different binding sites for cardiac glycosides (E2-P and E1-P) and involving a translocation of these drugs from an outer to an inner compartment of the cell membrane.

Adenosine Triphosphatases↗
PubMed1977

[Problems of combined therapy with cardiac glycosides and anti-anginal drugs (author's transl)].

The rational use of cardiac glycosides and anti-anginal drugs is deduced on the basis of the pathophysiological interdependence between cardiac and coronary insufficiency. With respect to therapeutic influence on myocardial function and oxygen balance the following rules ought to be regarded: 1. The use of cardiac glycosides should be restricted to patients with cardiac insufficiency in which these drugs are able to reduce the myocardial oxygen consumption due to the hemodynamic consquences of the positive-inotropic action. 2. Organic nitrates and/or beta-receptor blocking agents are compatible with simultaneous cardiac glycoside therapy, but both must be applied according to the individual requirement. 3. Coronary dilators are of questionable value in the therapy of coronary insufficiency, an additional advantage of a combination with cardiac glycosides still has to be proven. 4. There is no rational basis for the use of fixed combinations of these drugs, they do not allow effective and/or safe therapy.

Adrenergic beta-Antagonists↗
PubMed1975

Inotropic action, myocardial uptake and subcellular distribution of ouabain, digoxin and digitoxin in isolated rat hearts.

In experiments on isolated, electrically driven (240/min) rat hearts, perfused via the aorta at a constant flow (3.8 ml/min), the pharmacologically effective concentration range, the myocardial uptake and the subcellular distribution of three cardiac glycosides (digitoxin, digoxin, ouabain) were determined. The following results were obtained: 1. The effective range varied depending on the cardiac glycoside tested: With digoxin and ouabain very similar results were found- the positive inotropic concentration ranges being within 8x10(-6)M and 6x10(-5)M, the maximum positive inotropic effects attainable being about 100% and the concentration for half maximum effects (ED-50) being 2.4x10(-5)M and 2.3x10(-5)M, respectively. With digitoxin the inotropic concentration range was found to be within 3.6x10(-6)M and 2.4x10(-5)M with a maximum inotropic effect attainable of about 50% only and an ED-50 of 9.5x10(-6)M. The analysis of the time course of the inotropic action revealed extremely short half times for all cardiac glycosides studied (between 48 and 54 sec). 2. The myocardial uptake correlated with the physicochemical behaviour of the three cardiac glycosides studied and was found-depending on the perfusion time (5 to 60 min)-to be in the range of 23 and 36 (ouabain), 66 and 98 (digoxin) and 169 and 264 (digitoxin) nmoles/g wet weight. The respective computed half times for these uptake processes were 2.5 min (digoxin, ouabain) and 3.4 min )digitoxin). 3. Regarding the subcellular distribution an accumulation exceeding an "unspecific" binding (non-perfused hearts) was found mainly in the nuclear-membrane fraction. On the basis of these results (very short half times of either the pharmacological action and the cardiac uptake) the site of action of cardiac glycosides in the rat heart is supposed to be located at the surface membrane of the heart muscle cells. Furthermore, the above results are discussed with respect to those obtained in digitalis-sensitive species.

Animals↗
PubMed1975

Dependence of the cardiac uptake of digitalis glycosides on the extracellular calcium concentration in guinea pig isolated hearts.

The purpose of the present study was to investigate, at the myocardial level, the divergent influences of Ca2+ on the action of various cardiotonic steroids. Therefore, the cardiac uptake of 3-H-digitoxin and 3-H-digitoxin was studied in experiments on guinea pig isolated hearts. The following results were obtained: with digitoxin the increase of the extracellular calcium concentration from 0.45 upto 7.2 mM resulted in a concomitant decrease of the myocardial glycoside uptake from about 1.8 nmoles/g wet weight down to about 1.2 nmoles/g wet weight. Similar results were obtained when digoxin uptake was studied under the same conditions: with 0.45 mM Ca2+ about 0.6 nmoles/g wet weight were bound, increasing the calcium concentration upto 7.2 mM lead to a concomitant decrease of the cardiac digoxin uptake down to about 0.45 nmoles/g wet weight. Despite the different physicochemical behaviour of these two drugs and the different amounts of drug present in the hearts the influence of Ca2+ was almost identical if calculated on a relative basis. So far, no experimental based explanation can be given for the above discrepancies. Other possible interpretations are discussed.

Animals↗