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At least 253 records · Page 14Linked to original sources
PubMed1982

[Hemodynamic examinations concerning the effects of cardiac glycosides in hypertrophic obstructive cardiomyopathy (HOCM)].

Due to fundamental considerations and especially after Braunwald's et al. (1962 (4)) examinations of 5 patients with severe hypertrophic obstructive cardiomyopathy (HOCM) with 0.5-0.75 mg of Ouabain, cardiac glycosides in cases of this disease are to be regarded as contraindicated. Own examinations (right and left-heart catheterizations, monoplane cineangiography of the left ventricle, determination of the cardiac output, and the ejection fraction (EF) were performed in 10 patients with HOCM of different stages. Applying the usual dosage of 0.25-0.375 mg of strophanthin, different hemodynamic effects were observed in discrete forms. In cases with a higher severity, the observations of Braunwald et al. could actually be confirmed. The left ventricular systolic pressure gradients were increased, but cardiac output, left ventricular enddiastolic pressure, pulmonary pressure and resistance, and also arterial pressure and peripheral resistance behaved differently. EF increased slightly. The right infundibular gradients were decreased with one exception, or resp., they were unchanged. Obviously, HOCM reacts especially unfavourably with so-called left-ventricular cavity obliteration. The main importance might belong to the behaviour of the free lumen of the left ventricle. In regard of the principally reserved attitude towards the cardiac glycoside therapy in HOCM, no change has occurred. Only in patients with atrial fibrillation and a rapid heart rate, a therapy trial could be considered, if necessary in combination with beta-blocking agents or calcium antagonists under hemodynamic control. In cases of HOCM with serious obstruction and signs of cardiac failure and inadequate affecting by calcium antagonists, an early surgical intervention should be executed.

Adult↗
PubMed2026

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50 μM, and intracellular concentrations and cell viability were monitored over 48 h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry↗
PubMed1982

Studies on South African cardiac glycosides. II. Observations on the clinical and haemodynamic effects of cotyledoside.

In guinea-pigs, the oral and subcutaneous LD50 values were very similar (cf. 0,173 mg/kg over 48 h with 0,116 mg/kg over 24 and 48 h). When dosed subcutaneously, a cumulative effect was observed. Intravenous administration of cotyledoside to anaesthetized guinea-pigs resulted in: dyspnoea, increased heart rates and blood pressures, and electrocardiagraphic changes typical of cardiac glycoside poisoning. A positive cardiac inotropic effect was succeeded by a positive chronotropic one. In sheep, acute and subacute intoxication resulted in ruminal, respiratory and cardiac changes. The signs included ruminal stasis, cyanosis, cardiac arrhythmia, ectopic foci and AV dissociation, followed by hypotension and progressive respiratory and cardiac failure. The skeletal muscles were affected in only 1 sheep vide infra. In chronically intoxicated sheep typical clinical signs of "krimpsiekte" developed, e.g. weakness, reluctance to stand, unsteadiness on feet, tremor and paresis of hindquarter muscles, paresis of the neck, arching of the back and standing with the feet close together. Respiratory function was affected in all 3 cases; ruminal stasis, with concomitant loss of appetite occurring in one, and a transient change in heart function in another. The syndrome induced by acute cotyledoside poisoning is similar to that of other cardiac glycosides, but the paretic signs of chronic intoxication resemble "krimpsiekte", a disease associated only with intoxication with the plants of the family Crassulaceae.

Animals↗
PubMed1977

[Effect of treatment with cardiac glycosides and biologically active substances on the state of the lesser circulation according to the electrokymographic data].

Electrokymography was used to assess by pulmonary densograms and pulmonary artery pulse curves treatment-induced changes in cardiac contractility and lesser circulation in 455 patients with rheumatic heart disease and stage IIA, IIB, and III circulatory insufficiency. Treatment with cardiac glycosides in combination with metabolic preparations (ATP methionine, vitamin B12, inosine-F, and extract of the heart muscle) leads to a more conspicuous reduction in the symptoms of congestion in the lesser circulation than that encountered in treatment with cardiac glycosides alone. The reduction in these symptoms following treatment with ATP and heart-muscle extract may be explained not only by improved myocardial contractility but also by the direct vasodilating effect of adenyl compounds.

Adenosine Triphosphate↗
PubMed2002

Interactions of cationic drugs and cardiac glycosides at the hepatic uptake level: studies in the rat in vivo, isolated perfused rat liver, isolated rat hepatocytes and oocytes expressing oatp2.

This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide 2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance level should be based on data on the relative affinities of interacting substrates for the transport systems involved along with knowledge on the pharmacokinetics of these agents as well as the chosen dose regimen in the studied species. This review highlights the importance of multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic compounds of various charge, implying potential transport interactions that can affect body distribution and organ clearance.

Animals↗
PubMed1971

Metabolism of cardiac glycosides studied in the isolated perfused guinea-pig liver.

1. Metabolic degradation of tritiated ouabain, digoxin, and digitoxin has been investigated quantitatively using the isolated perfused guinea-pig liver. The cardiac glycosides and their metabolites have been extracted from the plasma, liver, and bile by different solvents and identified as far as possible by radio-chromatographic analysis.2. The total metabolic activity in the experimental system was localized in the liver.3. The hydrophilic glycoside ouabain could not penetrate into the metabolically active compartment of the liver and was, therefore, not degraded. The more lipophilic compound digitoxin, however, was completely degraded due to its high affinity for the metabolically active sites. The unchanged digitoxin cannot enter the aqueous bile fluid in contrast to its more hydrophilic metabolites.4. The only detectable metabolic degradation of digoxin was a conjugation with glucuronic and/or sulphuric acid, but a cleavage of sugar molecules seemed not to occur.5. In the case of digitoxin the metabolic processes are more complicated: sugar cleavage, conjugation, and C-12 hydroxylation take place simultaneously. An immediate hydroxylation of digitoxin leading to digoxin was not observed. After administration of digitoxin conjugation products as well as digoxigenin-bis-and digoxigenin-mono-digitoxosides were present in each of the compartments investigated, but the digitoxosides of digitoxigenin were intermediates in concentrations too low to be determined indicating a very high rate of conjugation and/or C-12 hydroxylation as compared with the cleavage of the digitoxoses.6. A scheme for the metabolic pathways of the cardiac glycosides based on experimental results is presented. The metabolic behaviour of each of the three compounds involved is closely related to their physicochemical properties, especially the lipid solubility.

Animals↗
PubMed1991

Microbiological exploitation of cardiac glycosides and alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia.

The four medicinal plants, Garcinia kola (roots), Borreria ocymoides (leaves), Kola nitida (bark) and Citrus aurantifolia (roots) were screened for phytochemical components. They were found to contain tannins, phlobatannins, polyphenols, hydroxymethyl anthraquinones, glucides, saponins, alkaloids, cardiac glycosides, flavanoids and reducing compounds. The aqueous and alcoholic extracts as well as alkaloids and cardiac glycosides of the medicinal plants were tested on various pathogenic bacteria. They were found to inhibit such organisms as Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, beta-haemolytic streptococci, Escherichia coli and Neisseria gonorrhoeae. The usefulness of the phytochemical bases of these plants as potential sources of pharmaceutical drug preparation is discussed.

Alkaloids↗
PubMed1984

Sugar moiety of cardiac glycosides is essential for the inhibitory action on the palytoxin-induced K+ release from red blood cells.

Palytoxin (PTX), a highly toxic and sugar-containing substance isolated from Palythoa tuberculosa, caused K+ release from rabbit red blood cells. Cardiac glycosides, such as ouabain, convallatoxin, cymarin, digoxin and digitoxin, inhibited the PTX-induced K+ release. Their corresponding aglycones did not inhibit the K+ release, but antagonized the inhibitory effect of the glycosides. All these cardiotonic steroids equally inhibited the activity of (Na+ + K+)-ATPase prepared from hog cerebral cortex. These results suggest that the sugar moiety of the cardiac glycosides is important for the inhibitory effect on the K+ release induced by PTX and that the inhibition is not related to their inhibitory potency on the (Na+ + K+)-ATPase activity.

Acrylamides↗
PubMed1997

Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain.

BACKGROUND: Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. To examine whether cardiac glycosides also modulate cytokine production, we evaluated the effects of ouabain on the production of cytokines in vitro and in vivo. METHODS AND RESULTS: Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers. PBMC were cultured with or without ouabain in the presence or absence of lipopolysaccharide (LPS). Ouabain induced the production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in PBMC and induced mRNA of these cytokines, an induction apparently at the transcriptional level. Amiloride, staurosporin, and genistein inhibited cytokine production, and protein kinase C and tyrosine kinase appeared to be involved in the modulation of cytokine production induced by ouabain. However, when PBMC were stimulated with LPS, ouabain suppressed the production of IL-6 and TNF-alpha. To investigate whether ouabain modulates cytokine production in vivo, we evaluated the effects of ouabain in LPS-treated mice. Ouabain was found to protect against LPS-induced lethal toxicity in mice and decreased circulating IL-6 and TNF-alpha levels in vivo. CONCLUSIONS: These previously unrecognized immunomodulating effects of a cardiac glycoside may explain either the beneficial or the detrimental effects of these drugs in heart failure patients.

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↗
PubMed1987

Effect of praziquantel on the cardiotonic action of cardiac glycosides.

The effect of praziquantel on isolated left guinea-pig atria has been studied. Praziquantel caused a concentration-dependent increase in the force of contraction of the isolated left atria, an effect which may be due to an increase in Ca++ fluxes. Praziquantel antagonized the cardiotonic effect of cardiac glycosides on guinea-pig atria. This antagonism is neither due to an alteration of Ca++ concentration in the cell, nor to a direct action on Na+, K+-ATPase, nor to inhibition of the binding of cardiac glycosides to heart tissue. This interaction may involve an enhancement of K+ fluxes in cardiac cells under the influence of praziquantel.

Animals↗
PubMed1988

N-(3-(p-azido-m-[125I]iodophenyl)propionyl)-succinimide--a heterobifunctional reagent for the synthesis of radioactive photoaffinity ligands: synthesis of a carrier-free 125I-labeled cardiac glycoside photoaffinity label.

A new heterobifunctional reagent, N-(3-(p-azido-m-iodophenyl)propionyl)-succinimide (AIPPS), was synthesized and chemically characterized. The radiochemical form of the reagent, [125I]AIPPS, should be of general use as a photoactive reagent for the derivatization of free amino groups on a large variety of biologically active compounds, including many hormones. Amino-containing ligands can be derivatized with [125I]AIPPS in a method which is similar to that used for the 125I-labeled Bolton-Hunter reagent (N-(3-(p-hydroxyphenyl)propionyl)-succinimide). The added advantage with [125I]AIPPS, however, is that the ligand derivative is made both photoactive and radioactive in a single step. As an example of how this reagent can be used, we have prepared carrier-free [125I]AIPPS and reacted it with the amino-containing cardiac glycoside, 4-amino-4,6-dideoxyglucosyl digitoxigenin (GluD). The radioiodinated cardiac glycoside, [125I]AIPP-GluD, was purified by thin-layer chromatography and was carrier-free with a specific radioactivity of 2175 Ci/mmol. [125I]AIPP-GluD was an effective photoaffinity label for Na,K-ATPase as shown by specific photoaffinity labeling of purified canine kidney enzyme and human erythrocyte enzyme.

Affinity Labels↗
PubMed1989

Skeletal muscle Na,K-pump concentration in children and its relationship to cardiac glycoside distribution.

Skeletal muscle Na,K-pump (cardiac glycoside receptor) concentration was quantified in 18 0- to 8-year-old human subjects by vanadate facilitated [3H]ouabain binding to intact vastus lateralis samples obtained at autopsy. No age-dependent change in [3H]ouabain binding site concentration was observed. Mean value +/- S.E.M. was 268 +/- 17 pmol/g wet wt. (n = 18), range 182 to 433 pmol/g wet wt. At the age of 1 day, 3.5 month and 8 years and 8 months, unspecific uptake and retention of [3H]ouabain was 1.6, 1.4 and 1.5% of the total uptake and retention; release of specifically bound [3H]ouabain during the washout procedure took place with T 1/2 of 97, 90 and 73 hr; and apparent affinity constants for [3H]ouabain binding (KD) was 1.3 x 10(-8), 0.9 x 10(-8) and 1.2 x 10(-8) mol/l. [3H]Ouabain binding site concentrations and kinetics were in agreement with values from adults except that in children apparent affinity constant (KD) was 1.7 times the value in adults. The observation of no age-dependent changes in human skeletal muscle Na,K-adenosine triphosphatase concentration was at variance with the observations of such changes in animals. The total number of Na,K-pumps in the pool of skeletal muscles increased from 10 to 50 times that in the heart from birth to old age. The skeletal muscle pool of Na,K-pumps seems to constitute a distribution volume of importance during digitalization in children as well as adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1996

Effect of two cardiac glycosides, digitoxin and digoxin on blood lipids.

Two cardiac glycosides, namely digitoxin and digoxin when treated with goat blood, were found to alter the lipid constitution as measured by their phosphorus content, fatty acid composition and malonaldehyde content. There was significant increase in the poly-unsaturated fatty acids (PUFA) and malonaldehyde contents in blood treated with these drugs. Possible correlation between the lipophilicity of the drugs and their biological activity is discussed.

Animals↗