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Biomedical subjects

W Klaus

Publications and source records attributed to W Klaus.

At least 109 records · Page 6Linked to original sources
PubMed1987

Influence of derivation on the lipophilicity and inhibitory actions of cardiac glycosides on myocardial Na+-K+-ATPase.

Lipophilicity and inhibitory actions on guinea-pig heart Na+-K+-ATPase of twenty-six digitalis and six strophanthus glycosides comprising the aglycones, mono-, bis-, tris-sugar, alkylated (acylated) tris-sugar, acyl steroid derivatives and three cardanolides were investigated. Their octanol/water partition coefficients (P), reversed phase thin layer (r.t.l.c.) and reversed phase high performance liquid chromatography (r.h.p.l.c.) were determined and the viability of these methods as a measure of the lipophilicity of the cardiotonic steroids evaluated. The influence of lipophilicity and so also structural changes on the inhibitory effects of the cardiac glycosides on myocardial Na+-K+-ATPase was then examined. It is concluded that (a) r.t.l.c. and r.h.p.l.c. are just as effective as the conventional shake-flask method for estimation of the lipophilicity of cardiac glycosides and (b) the inhibitory potencies of cardiotonic steroids on the myocardial Na+-K+-ATPase increase with growing lipophilicity. The relationship between these two parameters is, however, governed by the influence of substitution or derivation of structural components on their inhibitory potencies on the myocardial Na+-K+-ATPase.

Animals↗
PubMed1987

Different sensitivities of arteries and veins to glyceryltrinitrate-induced relaxation and tolerance: an "in vitro" study on isolated vessels from rabbits.

Glyceryltrinitrate (GTN)-induced relaxation was examined in helical strips of rabbit femoral and mesenteric vessels after precontraction with norepinephrine (EC-50). Concentration-response curves over a wide concentration range (10(-9) to 3 X 10(-4) mol/l) appeared to be biphasic with a plateau at 10(-6) mol/l. Threshold concentrations for relaxation (EC-10) were different in arteries (2 X 10(-8) mol/l) and in veins (2 X 10(-9) mol/l), indicating a higher sensitivity of veins than of arteries to low concentrations of GTN. After induction of GTN-tolerance (60 min preincubation with EC-90) the arterial vessels revealed a monophasic concentration response curve (EC-10: 10(-6); EC-50: 10(-5) mol/l). The relaxation at the lower concentration range was abolished (shift to the right at lower GTN-concentration). On the other hand, in veins the concentration-response curve was completely shifted to higher concentrations (EC-10: 10(-8) mol/l) and the high sensitivity component was diminished to 50%. However, the enhanced sensitivity of veins in comparison to arteries was preserved. 10(-3) mol/l cystein was unable to affect tolerance in arteries, but partially reversed the development of tolerance effects in veins. Moreover, 10(-6) mol/l indomethacin could mimic GTN-tolerance in arteries but not in veins. Thus, relaxation as well as tolerance induced by GTN, seem to be mediated at least by 2 different mechanisms. Only in arteries the prostaglandin system appears to be involved. On the other hand depletion of SH-groups seems to play a major role in veins in agreement with the hypothesis of Ignarro et al. (1981).

Animals↗
PubMed1986

[The antitoxic action of triamterene in cardiac glycoside poisoning].

The antagonistic effect of triamterene on the toxicity of cardiac glycosides was investigated in conscious rabbits using the infusion method. Pretreatment with triamterene (5 mg/kg and 10 mg/kg) significantly reduces the ouabain toxicity indicated by an increase of the dose producing arrhythmia (from 61 +/- 14 to 121 +/- 17 and 178 +/- 22 micrograms/kg, resp.) and lethality (from 114 +/- 18 to 236 +/- 5 and 329 +/- 11 micrograms/kg, resp.). The triamterene induced increase of plasma potassium concentration may contribute to the antitoxic effect, however, the effect persisted after the decrease of plasma potassium concentration (by addition of NaHCO3) to pretreatment values. Under the influence of digitoxin the antitoxic effect of triamterene (10 mg/kg) is also demonstrated by the delayed appearance of arrhythmias (113 +/- 3 min compared to 78 +/- 5 min) and of lethality (125 +/- 4 min compared to 92 +/- 6 min). Triamterene is not only a prophylactic but also a curative antitoxic agent in the digitalis intoxicated rabbit.

Animals↗
PubMed1985

[Inhibition of platelet aggregation and thromboxane formation by the calcium antagonist nisoldipine following a single oral dose of 10 mg. A double-blind study in healthy probands].

The influence of the calcium antagonist nisoldipine on collagen-induced platelet aggregation and platelet thromboxane formation was studied ex vivo in healthy male volunteers in a double-blind, placebo-controlled crossover design. Measurements of general haemodynamics, immunoreactive 6-oxo-prostaglandin F1 alpha and thromboxane B2 ex vivo and collagen-induced (0.6 and 2.5 micrograms/ml) platelet aggregation were performed immediately before (time 0), 0.5 h, 1 h and 2 h after ingestion of 10 mg nisoldipine or an identical placebo tablet. Compared with the control response at time 0, administration of nisoldipine resulted in a significant inhibition of both low-collagen-induced platelet aggregation and formation of immunoreactive thromboxane B2 at time 0.5 h. There were no changes in heart rate or systolic blood pressure but a significant decrease in diastolic blood pressure by nisoldipine at 1 h. No such change was obtained with placebo and there were also no alterations with nisoldipine in platelet aggregation and thromboxane formation after stimulation by high-dose collagen at this or any other time of the study. The data demonstrate a platelet-inhibitory potential of nisoldipine in healthy men which is probably related to an increased resistance of the platelet membrane against foreign stimuli.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

31P-NMR spectra of AP4.

31P-NMR spectra were obtained from adenosine-5'-tetraphosphate under a variety of conditions and the four discernible resonances assigned. The pK-value of the metal-free compound was determined to be 6.4, the pK-value of the Mg2+ complex to be 5.3. The dissociation constant for the AP4 X Mg2+ complex was estimated to be 10(-4) M from the downfield shift of the resonances assigned to the gamma- and delta-phosphorus nuclei. The binding of a second metal ion can also be followed by NMR; the dissociation constant for this ternary complex is several orders of magnitude larger than that for the binary complex.

Adenine Nucleotides↗
PubMed1985

Epicardial image analysis using a desk top computer. Comparison of epicardial flow distribution and NADH-fluorescence pattern.

In isolated coronary-ligated rabbit hearts, quantification of epicardial flow distribution pattern and of ischemic area was performed from flow indicator and endogenous NADH-fluorescence pictures, respectively, after UV-flash photography. After being digitized (256 X 256 pixels), the fluorescence photos were analyzed by an Apple desk computer using self-written software (fast machine routines called from BASIC programs). The ischemic area (= sum of pixels with enhanced NADH fluorescence) corresponds to the area with disturbed coronary perfusion (= sum of pixels with diminished indicator fluorescence). Since coronary-active drugs might affect both parameters--local myocardial perfusion and metabolism--differentially, the method presented seems to be a very useful technique for differentiated analysis of the action profile of coronary-active drugs.

Animals↗
PubMed1984

[Pharmacology of calcium antagonists].

The present increase in indications for application of calcium antagonists--beyond the area of coronary heart disease--is confirmed by pharmacological analyses. Due to calcium antagonists the contractility is decreased, which is followed by a decreased oxygen consumption in the heart and a relaxation of the vessels. Nowadays, the anti-arrhythmic and cardio-protective effects as well as the prevention of coronary spasms by these substances can be pharmacologically established.

Angina Pectoris↗
PubMed1984

Reduced transcoronary exchange and prostaglandin synthesis in diabetic rat heart.

In perfused hearts of streptozotocin-diabetic rats the kinetics of a fluoresce indicator transit was measured after pulse injection of FITC-dextran 3. The fluorescence changes on the left ventricle could be described by two pseudo first-order processes with half times in the range of seconds (t/2) corresponding to the intravascular washout and a slow process (T/2) corresponding to the exchange between the extra- and the intravascular space. In diabetes both half times became prolonged, and the amount of FITC-dextran 3 exchanged between the two compartments was reduced, indicating an impaired transcoronary transport in diabetic hearts. There was a time-dependent reduction in the basal release of prostacyclin in hearts of control and diabetic rats. However, studied hearts of diabetic rats released less 6-keto-prostaglandin F1 alpha (PGF1 alpha) than controls. This impaired release of 6-oxo-PGF1 alpha could be prevented partly by adrenalectomy. Because diabetic hearts release more 6-oxo-PGF1 alpha than controls after application of arachidonic acid, these data suggest that the supply of arachidonic acid for the synthesis of prostaglandins is impaired in diabetes, but not the cyclooxygenase pathway itself. The reduced transcoronary transport and the impaired synthesis of prostacyclin might be early steps in the development of microangiopathic myocardial alterations in diabetes.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

The mechanical atrioventricular time of isolated hearts as a correlate of the atrioventricular conduction time.

The time difference between onset of contraction in right atrium and left ventricle of isolated guinea pig hearts (mechanical AV time) was measured continuously by an impulse-triggered interval counter and taken as an equivalent of the electrophysiological AV conduction time derived from the epicardial ECG. Excellent correlation between these two parameters was established over a broad range of experimentally modified conduction times. The method was used to analyze the influence of electrical pacing, epinephrine, Ca2+ ions, and adenosine both on the AV conduction and on functional parameters of the hearts and revealed advantages in comparison to separate tests of single parameters in different experimental arrangements.

Adenosine↗
PubMed1982

Effects of calcium on ouabain-induced inotropism in rat and guinea pig hearts.

In experiments on isolated rat and guinea pig hearts, the influence of different calcium concentrations (0.45-3.6 mM) on ouabain action was studied. A different time course of the inotropic action of ouabain in rat heart (t1/2 about 15 sec) and guinea pig cardiac muscle (t1/2 about 4 min) was found. Furthermore, compared to guinea pig hearts, a considerably enhanced "sensitivity" of the rat myocardium to ouabain at increased calcium concentrations could be established. These results are explained on the basis of a different mode of calcium in modulating the contractility within these two species.

Animals↗
PubMed1982

Influence of carbocromen on some metabolic parameters of isolated working guinea pig hearts.

The influence of carbocromen (chromonar) on both functional and some metabolic parameters of isolated guinea pig hearts was tested over a broad concentration range and with different exogenous substrates. As revealed from a shift of the myocardial respiratory quotient, carbocromen (in the upper coronary active concentration range) induced an increased glucose utilization at the expense of FFA oxidation. Theoretically, this may indicate a relative reduction of myocardial oxygen demand, but the therapeutic relevance of this observation still remains obscure, as an additional exogenous FFA supply may override this biochemical carbocromen effect.

Animals↗
PubMed1981

Active site-directed alkylation of Na+-K+-ATPase by digitalis sulphonate derivatives of different lipophilicity.

1 Sulphonate derivatives of k-strophanthidin and digitoxigenin were tested as active site-directed labels of Na+-K+-adenosine triphosphatase (Na+-ATPase) from guinea-pig heart. 2 Lipophilicity ranged between P = 93 for strophanthidin-3-tosyloxy-acetate (STA) and P = 3028 for digitoxigenin-3-tosyloxy-acetate (DTA). 3 Although the alkylating moiety of STA and DTA was identical, the reversibility of Na+-K+-ATPase inhibition varied appreciably (82% and 35% respectively). 4 It is concluded that lipophilicity contributes considerably to the irreversible binding of alkylating cardiotonic steroids to myocardial Na+-K+-ATPase.

Alkylation↗