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At least 235 records · Page 13Linked to original sources
PubMed1993

Digitalis restores the forearm sympathetic response to cardiopulmonary receptor unloading in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To investigate whether the impaired reflex response to cardiopulmonary baroreceptor unloading in hypertensive patients with left ventricular hypertrophy can be promptly improved by a pharmacological challenge. For this purpose we studied the effects of acute digitalis administration on cardiopulmonary baroreflex, evaluated by forearm noradrenaline spillover. METHODS: Eleven hypertensives with left ventricular hypertrophy and 10 age- and sex-matched normotensives underwent the application of -5 and -10 mmHg lower-body negative pressure (LBNP) before and after the administration of digitalis. Forearm noradrenaline spillover, measured using a tracer technique, was used to estimate the reflex sympathetic response. RESULTS: Under control conditions LBNP evoked a similar fall in right atrial pressure in the two study groups. In the normotensives there was a significant increase in forearm noradrenaline spillover. In the hypertensives no significant changes in forearm noradrenaline spillover were found. Intravenous administration of 0.02 mg/kg lanatoside C was associated with an increase in systolic blood pressure and a reduction in forearm noradrenaline spillover in both groups. In the normotensives the percentage change in forearm noradrenaline spillover induced by LBNP increased significantly in response to digitalis administration. However, digitalis restored the response of forearm noradrenaline spillover to LBNP in the hypertensives, so that no significant difference in this response was detected between the two study groups. Digitalis did not modify the effects of LBNP on cardiac pressures in either group. CONCLUSIONS: The present results demonstrate that administration of lanatoside C restores the response of forearm noradrenaline spillover to cardiopulmonary baroreceptor unloading in hypertensive patients with left ventricular hypertrophy. This indicates that the impairment of cardiopulmonary baroreflexes in these patients can be reversed by acute pharmacological treatment. Therefore, impairment of this reflex response seems to be related to functional rather than to structural abnormalities of the hypertrophied ventricle.

Digitalis Glycosides↗
PubMed1959

The duration of action of some cardiac glycosides and aglycones in the guinea-pig.

A method is described for determining the duration of action of cardiac glycosides and aglycones in the guinea-pig. It is based on their property of potentiating the cardiac response to adenosine. The method is particularly suitable for those drugs with a short duration of action, whereas previous methods are more suitable for those drugs with longer durations of action. The duration of action of one-fifth of the lethal dose has been found for: digoxigenin, lanatoside C, ouabain, digitoxigenin-3-one, digitoxin, 3-acetyldigitoxigenin, digoxin, digitoxigenin, lanatoside A; these drugs are arranged in order of increasing duration of action. The possible relationship between the elimination of these drugs and their duration of action can provide an estimate of their rates of elimination.

Biological Transport↗
PubMed1978

Molecular basis of B cell activation: mitogenicity of native and modified digitalis glycosides.

Lanatoside C, a digitalis glycoside, has previously been shown to be a potent polyclonal B cell activator for mouse lymphocytes. Since the chemical structure of lanatoside C is well defined we investigated the effect of different chemical modifications on the mitogenic properties of the glycoside in order to determine the molecular basis of B cell activation. The presence of an OH- group at C12 in the steroid nucleus proved to be essential for activation to occur in serum-free medium. Likewise, an intact carbohydrate side chain at C3 appeared to be necessary for retaining mitogenic properties. In serum-supplemented cultures, however, a much more complex response pattern was observed where the prerequisites for activation were not as distinct as in serum-free medium.

Animals↗
PubMed1987

Human cell mutants affected in the interaction of the 12 beta-OH group of cardiac glycosides with the digitalis receptor.

The cross-resistance patterns of two different types of mutants of HeLa cells selected for resistance to the digoxin analog SC4453 (SCR mutants) in which the Na+/K+-ATPase is affected [A. Chopra and R. S. Gupta, J. biol. Chem. 261, 2034 (1986)], and towards numerous cardiac glycosides (CGs) and genins, were examined. One type of SCR mutant (designated as group C) was highly resistant to all CGs and genins investigated. In contrast, the other type of SCR mutant (group D) showed a high degree of cross-resistance towards selected CG derivatives (viz. digoxin, SC4453, digoxigenin, lanatoside C, alpha- and beta-methyldigoxin, dihydrodigoxin, alpha- and beta-acetyldigoxin, alpha,beta-diacetyldigoxin), all of which contained a free 12 beta-OH group in the steroid structure. Slight cross-resistance of the group D mutants was also observed for other compounds (viz. ouabain, ouabagenin, dihydroouabain) that contain a free 11 alpha-OH group in the molecule. However, these mutants exhibited no cross-resistance to other CG derivatives, which either lacked the above groups (viz. digitoxin, digitoxigenin, dihydrodigitoxin, digitoxigenin mono- and bisdigitoside, nerifolin, gitoxigenin, gitoxin, 16-acetylgitoxin, lanatosides A and B, cymarin, convallatoxin, oleandrin, strophanthidin, actodigin and bufalin) or in which the 12 beta-OH group was acetylated (viz. as in the case of 12-acetyldigoxin). Since the 12 beta-OH group is not required for CG-like activity, to account for these observations it is suggested that the genetic lesion in the group D mutant leads to the creation of a new binding site in the digitalis receptor, which specifically interacts with the 12 beta-OH group (the site presumably also interacts weakly with the 11 alpha-OH group) and either prevents or distorts the binding of the compounds to the drug binding site on the receptor. Further investigations with the different classes of CG-resistant mutants at the molecular level should prove very useful in identifying the drug receptor site and in understanding how these drugs interact with it.

Cardiac Glycosides↗
PubMed1983

[The contraction of intestinal myocells and block of cationic pumps].

The effects of a block of Na-K-ATPase pump on the contraction of intestinal smooth muscle (ileum of guinea pig) induced by carbachol has been analysed. Two parameters have been evaluated: a) maximum velocity of contraction (Vmax.C); b) maximum velocity of relaxation (Vmax.D) after washing. The block of pump is produced by a digitalic agent (desacetyl-lanatoside C). The application of 0.3 micrograms/ml of lanatoside for 1 min causes an increase of Vmax.C and a decrease of Vmax.D; whereas it does not influence the height of contraction. This effect is in agreement with the mechanism of action of Na on the contraction curve.

Animals↗
PubMed1986

Laser desorption/Fourier transform mass spectra of glycoalkaloids and steroid glycosides.

Positive- and negative-ion mass spectra of five glycoconjugates were obtained using laser desorption/Fourier transform mass spectrometry. These were the glycoalkaloids alpha-solanine and alpha-tomatine and the steroid glycosides gitoxin, lanatoside A and digitonin. Doping with KCl yielded both potassium- and chloride-attachment ions. Few fragment ions were observed for these species, with the exception of digitonin, although the negative-ion spectra showed relatively more fragmentation than the positive-ion spectra. All major fragments appeared to arise from losses of sugar groups due to cleavages at the glycosidic linkages. This contrasted sharply with the behavior of the malto-oligosaccharides studied in this laboratory.

Alkaloids↗
PubMed2006

Expression of recombinant Digitalis lanata EHRH. cardenolide 16'-O-glucohydrolase in Cucumis sativus L. hairy roots.

The coding sequence for the Digitalis lanata EHRH. cardenolide 16'-O-glucohydrolase was inserted downstream of the 35S promoter in the binary vector pBI121 resulting in plant expression vector pBI121cgh. Cotyledon explants excised from 10-day-old seedlings of Cucumis sativus L. were transformed using Agrobacterium rhizogenes 15834 harbouring pBI121cgh. Hairy roots were obtained from infected cotyledon explants in vitro 10 days after inoculation. PCR amplification of coding sequences for cgh I, rolB and rolC from Ri plasmid showed that the aimed sequences were inserted into the genome of transformed cucumber hairy roots. Glycolytic activity of the transgenic CGH I was measured by HPLC using Lanatoside glycosides as substrate. Therefore, the cgh I transformed cucumber hairy roots may provide a valuable model for biotransformation of natural compounds by recombinant enzymes.

Cardenolides↗
PubMed1990

Effects of crotoxin on the isolated guinea pig heart.

The effects of crotoxin, isolated from the venom of the South American rattlesnake, Crotalus durissus terrificus, were investigated on isolated guinea pig hearts, perfused with Locke solution, by the Langendorff method. The cardiac beats and the electrocardiogram were simultaneously registered and the creatine kinase (CK) activity of the perfusate measured. Crotoxin was infused (4.5 x 10(-8) M and 2.3 x 10(-7) M) into the heart during 90 min, and induced a remarkable decrease in the contractile force, without a significant reduction of heart rate, increased the P-R interval and displaced the S-T segment. The activity of CK only increased in the late phases of the experiments, when the force of contraction was below 25% of the control value. Arrhythmias were uncommon and no alterations of QRS duration or Q-Tc interval were observed. The reduction of the contractile force and the increase in CK activity were completely prevented by bovine serum albumin, whereas lanatoside C did not interfere with the toxin action. A bolus injection of crotoxin (11 +/- 2 nmoles) also induced a decrease of contractile force without reduction of heart rate. This decrease of force was partially prevented by indomethacin, but not by atropine. It is suggested that the reduction of contractile force evoked by crotoxin is due probably to release of free fatty acids and lysophospholipids (initial effect) and to a cellular lesion (late effect).

Albumins↗
PubMed1983

Modification of the baroreceptor control of atrio-ventricular conduction induced by digitalis in man.

Several studies in animals and in man have suggested that the inhibitory influence of baroreceptors on heart rate and peripheral circulation is enhanced by digitalis. Because the atrio-ventricular node represents a key site for the clinical action of digitalis we studied how baroreceptor control of atrio-ventricular conduction is modified by digitalis at therapeutical doses. In eight subjects heart rate was kept constant by atrial pacing to assess neural influences on atrio-ventricular conduction rate without the modifications caused by simultaneous changes in cardiac cycle length. Arterial baroreceptors were stimulated by increasing or reducing blood pressure (intra-arterial recording), via an iv bolus of phenylephrine or nitroglycerine. The baroreflex sensitivity was assessed in ms . mmHg-1 as the slope of the linear regressions relating the rise or fall in systolic blood pressure to the lengthening or shortening in St- (atrial stimulus artifact) Q interval (ECG recording). The study was performed before and 45 min after iv administration of digitalis (0.8 mg of Lanatoside C). Baroreflex sensitivity during baroreceptor stimulation was 2.9 +/- 1.1 ms . mmHg-1 (mean +/- SE) before digitalis, whereas after digitalis a significantly and markedly greater value of 5.6 +/- 1.5 ms . mmHg-1 was found. Baroreflex sensitivity during baroreceptor deactivation was 0.9 +/- 0.1 ms . mmHg-1 before digitalis, and was not significantly affected by the drug. Thus in man the baroreceptor control of atrio-ventricular conduction is strikingly potentiated by digitalis although this potentiation is only evident in the upper portion of the stimulus-response curve of the reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Treatment of paroxysmal supraventricular tachycardia in infancy with digitalis, adenosine-5'-triphosphate, and verapamil: a comparative study.

The treatment of paroxysmal supraventricular tachycardia (PSVT) in infancy with digitalis, adenosine triphosphate (ATP) and verapamil is reported. Treatment was successful in about 90% of the patients treated with ATP and verapamil and in 61--71% of the patients treated with digitalis (Lanatoside C). Verapamil terminated the tachycardia within 2 minutes of administration in most instances and ATP in less than 1 minute. Digitalis, however, took as long as 2 hours; it was therefore excluded as the drug of first choice in emergencies, and is better suited for treating patients with poor hemodynamics. Side effects with ATP are common but short-lived. With verapamil, side effects are rare, but may be serious if certain contraindications are not taken into account. Digitalis in the dose used in this trial rarely produced side effects. We conclude that ATP or verapamil is the drug of first choice for quick termination of PSVT in infancy.

Adenosine Triphosphate↗
PubMed1978

[Use of digitalis glycosides in severe disorders of intra-ventricular conduction].

The use of digitalis in severe disorders of intra-ventricular conduction is debatable, and some consider it contra-indicated. Once it had been shown that the latter attitude is at best based on contraversial theoretical arguments, two types of study were undertaken: 1. Nine patients with bilateral bundle branch block had intracavitary recordings made of the HV interval both before and for one hour after the administration of lanatoside C (0.8 to 1.6 mg). In no case was this interval found to be increased, indicating that there was no increase in the original conduction defect. 2. Thirty four patients with complete right bundle branch block and associated left antero-superior hemiblock were digitalised, and followed up for an average of 16 months; only 2 complete atrio-ventricular blocks occurred (5.9%). The risk of complete atrio-ventribular block occurring within a year (4.5% in our series) does not differ significantly from that in an identical control group of 38 patients with the same conduction defect, but who were not digitalised (6%). Three patients had a therapeutic overdose of digitalis with no observed increase in their atrio-ventricular block. The authors conclude that it is perfectly in order to digitalise a patient with a severe intra-ventricular conduction defect.

Aged↗
PubMedDate not supplied

Clinical utility of plasma digoxin measurements.

The results of plasma digoxin concentration (PDC) measurements in 260 patients treated with digitalis lanata preparations (digoxin, lanatoside C, betamethyl-digoxin) allowed the following observations: 1. Owing to an important overlap between "toxic" and "nontoxic" PDC values, the method has a limited value in the diagnosis of digitalis toxicity. However, in patients with toxicity associated with PDC under 2 ng/ml, it allows identification digitalis sensitivity. 2. A dosage selection based on PDC assessment led to a decrease of digitalis toxicity under 4%. As the method is not widely available, it has to be used in patients with borderline renal function, in aged subjects and in patients with rapid atrial fibrillation who require higher digitalis doses for heart rate control.

Adult↗
PubMed1979

[Creatine phosphokinase release from perfused cardiac muscle under hypoxic conditions. Effect of propranolol, verapamil, reserpine and deslanoside].

Experiments were undertaken to determine if some drugs (propranolol, reserpine, verapamil and deslanoside) have an effect on CPK release from hypoxic heart muscle. Hypoxia was induced in isolated Langerdorff perfused rabbit hearts by gassing the perfusate with 95% N2 + 5% CO2. Hypoxic induced damage of the rabbit heart muscle has been quantited in terms of the relase of the intracellular enzymes creatinephosphokinase (CPK) into the extracellular space. Propranolol was either added at the start of the hypoxic perfusion or the rabbit were pretreated with it. Verpamil, dl-propranolol and reserpine provided protection evidenced by a reduction of hypoxic induced CPK release, while lanatoside C and d-propranolol failed to prevent the hypoxic muscle from releasing CPK.

Animals↗
PubMed1978

[The clinical significance of plasma glycoside concentrations in patients with cardiac pacemakers (author's transl)].

308 digitalized out-patients with artificial cardiac pacemakers were explored for signs of glycoside toxicity with simultaneous determination of digoxin plasma levels 12 hours after the last dose. The incidence of different side effects commonly attributed to overdigitalization did not allow prediction of toxic plasma levels. 55% of all glycoside levels were within the therapeutic range, 34% were below 0.7 ng/ml and only 11% above 2.0 ng/ml. With the most commonly prescribed maintenance doses of the glycosides used (digoxin 0.5 mg, beta-acetyldigoxin 0.4 mg, beta-methyldigoxin 0.2 mg, lanatosid C 1.0 mg) therapeutic plasma levels were reached regularly in 60-65% of the patients. A significant correlation existed between plasma glycoside concentrations and renal function as well as age, but glycoside concentrations could not be correlated with the age of the patients. There were no indications for interactions of the different glycosides prescribed with diuretics or oral antidiabetics.

Adult↗
PubMed1982

[Effect of digitalis on hemodynamics during rest in patients with arterial occlusive diseases, stage II, without cardiac insufficiency].

In 6 patients without clinical symptoms of myocardia insufficiency and with stage II occlusive disease of the femoral artery, blood flow volume at rest, arterial blood pressure and heart rate were measured before, during and for two hours after an iv. infusion of 1.0 mg desacetyl-lanatoside. Blood flow at rest decreased by 23% and peripheral vascular resistance increased by 34%. The increase in the blood pressure amplitude was compensated by a decrease in heart rate. The mechanism of action is discussed. It is concluded that patients suffering from stage II arterial occlusive disease do not benefit at rest from the prophylactic administration of digitalis.

Aged↗
PubMedDate not supplied

Value of systolic time intervals in the estimation of heart failure secondary to acute myocardial infarction.

Serial measurements of left ventricular systolic time intervals (STI) were carried out in 44 patients with acute myocardial infarction (AMI) in the first 5 days after onset, by indirect methods. The patients with heart failure showed significant decreases of ejection time (ET) (p less than 0.001) and of the ejection time index (p less than 0.005) and increases of Wiessler's ratio (PEP/ET) (p less than 0.001). The pre-ejection period (PEP), the isovolumetric contraction time and the total electromechanical systole were unsignificantly changed. Ejection time was shorter than 250 msec in the patients with acute pulmonary edema or congestive heart failure, in most of the patients with flutter or atrial fibrillation and in 16 of the 17 patients who died. Ejection time may have a prognostic significance and may be useful in the early detection of heart failure in AMI. The changes of STI after administration of lanatosid C show the positive inotropic effect of this drug in patients with AMI.

Adult↗
PubMed1986

Cellular basis for the species differences in sensitivity to cardiac glycosides (digitalis).

The relative toxicity of numerous cardiotonic steroids (viz. ouabain, digitoxin, digoxin, convallatoxin, SC4453, bufalin, gitaloxin, digoxigenin, actodigin, oleandrin, digitoxigenin, gitoxin, strophanthidin, gitoxigenin, lanatosides A, B and C, alpha- and beta-acetyl digoxin, alpha- and beta-methyl digoxin) and related compounds towards a number of independent cell lines established from human, monkey, mouse, Syrian hamster, and Chinese hamster have been determined. All cardiac glycosides and their genins, as well as the cardiotonic alkaloid cassaine, exhibited greater than 100-fold higher toxicity towards cultured human and monkey cells in comparison to the cell lines of mouse, Syrian hamster, and Chinese hamster origins. These differences are species-related as all cell lines (both normal as well as transformed) from any one species, as well as cells from the closely related species (e.g., man and monkey or mouse, Chinese hamster, and Syrian hamster), showed similar sensitivity towards these drugs. The failure to see any significant differences in cellular toxicity for a larger number of other compounds which either bear limited structural resemblance to cardiac glycosides (viz. estradiol 17-beta-acetate, testosterone propionate, 21-acetoxy pregnenolone, beta-estradiol, digitonin, tigogenin, and tomatine) or interact with the Na+/K+ ATPase in a different manner (viz. veratridine, sanguinarine nitrate, penicillic acid, vanadium pentoxide, harmaline-HCI,5,5'-diphenyl hydantoin, quindonium bromide, and methyl quinolizinum bromide) provides strong evidence that the observed species-related differences are highly specific for cardiotonic steroids. Studies on the binding of [3H]ouabain show that, in comparison to human and monkey cell lines, no significant binding of the drug is observed in cells derived from the resistant species (i.e., mouse and Chinese hamster). The Na+/K+ ATPase from cells of the resistant species is inhibited at much higher concentrations of ouabain and digitoxin in comparison to the enzyme from human cells, and a good correlation is observed between these concentrations and those reported for inhibition of the enzyme from isolated heart muscles of the same species. These results provide strong evidence that the species-related differences in sensitivity to digitalis have a cellular basis and that the cultured cells from various mammalian species provide a useful model system for investigating the mechanism of action of cardiac glycosides.

Animals↗