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[Contracted endocardial fibroelastosis in children: report of a case].

Endocardial fibroelastosis is un uncommon disease and it has a very bad prognosis since fatal evolution is usual before 2 years old. We report the case of a 20 years old woman who is affected with the contracted form of this disease associated with atrial septal defect (ASD) and mitral regurgitation. This disease was discovered by endocardial biopsy when she was 4 years old and underwent surgical resection of endocardial fibrosis, a patch on the ASD and mitral valve replacement. She was rehospitalised 15 years later with heart failure although continuous digitoxin therapy.

Adult↗

Digoxin: placental transfer, effects on the fetus, and therapeutic use in the newborn.

Digoxin rapidly crosses the placenta and reaches equilibrium, with maternal and fetal sera having equal concentrations. Virtually nothing is known about the effects of transplacentally administered digoxin on the fetus. Toxicity has been reported in the fetus of a woman ingesting a huge overdose of digitoxin; the same result would be anticipated with digoxin poisoning. Serum levels in pregnant women receiving the standard dose of 0.25 mg tend to be subnormal and certain patients may require a small increase in dose during the last trimester. While the full-term neonate appears to tolerate relatively high doses and the resultant high serum levels, there is no compelling evidence that such doses are necessary or even useful. Since toxicity can and does occur in neonates, especially during administration of loading (digitalizing) doses, it is recommended that maintenance doses of 0.01 mg per kg per day be used routinely. If the full inotropic effect is needed immediately, a loading dose of 0.03 mg per kg may be employed. Maintenance therapy is then begun on the following day. Without a loading dose cumulation occurs for about 3 days; after 5 or so days, serum levels will equal those found after use of a loading dose followed by maintenance therapy. Results of a single study suggest that the daily dose should be divided and given every 12 hours. After about 1 week of therapy, the serum level should be determined and the dose modified to maintain a serum level of 1 to 2 ng per ml. If the therapeutic effect is less than desired, a cautions increase in dose to as high as 0.02 mg per kg per day or to that dose which produces serum levels up to 3 ng per ml can be tried. Certain infants appear to tolerate serum levels of 3.5 to 4 ng per ml but such infants must be closely monitored. There are no data which indicate that a greater inotropic response will occur at these high serum levels, though this point has not been definitively investigated, and is the highest priority question for research. The intramuscular route should be researved for the unusual situation. Vomiting should be considered an early sign of toxicity and may act as a "safety valve." When adminstered in solution (as in the elixir or solution for intravenous use), oral digoxin is rapidly absorbed an an inotropic response is found within minutes, reaching a peak within hours, so that little is gained by parenteral administration. If an inotropic effect is urgently needed, intravenous administration of ouabain will give an immediate response.

Animals↗

Clinical practice--improving instruction and evaluating performance.

The cardiac glycoside, ouabain, normally kills HeLa cells at concentrations of about 10-7 M or greater. By treating a population of HeLa cells with increasingly higher concentrations of the drug, a variant population was obtained of HeLa cells capable of growing in medium containing 10 minus 4 M ouabain. Inhibition of volume regulation of cells subjected to hypotonic shock was used as a measure of inhibition of active transport of Na across the plasma membrane. In that way dose-response curves for the rapid effects of ouabain and other inhibitors of active Na transport were obtained with both the original, ouabain-sensitive (OS) and the variant, ouabain-resistant (OR) cells. Three other cardiac glycosides (digoxin, digitoxin and hellebrin) and two aglycones (digitoxigenin and strophanthidin) were found to be equally as effective as ouabain in inhibiting volume regulation of the OS cells; the concentration which produced half-maximum inhibition, I(max/2), was about 6 X 10 minus 7 M in each case. Similar inhibition of the OR population by ouabain was observed only when the concentration exceeded 10 minus 4 M [I(max/2)2.5 X 10 minus 4 M], and the other steroid compounds had no effect on the variant cells at the highest concentrations tested (2 X 10 minus 5 M). OR and OS cells differed also in their sensitivities to the cardioactive erythrophleum alkaloid, coumingine; I(max/2) for OS and OR cells was 5 X 10 minus 8 M and 6 X 10 minus 7 M, respectively. These results, in addition to results of ouabain binding experiments and measurements of the rates of reversal of inhibition of volume regulation, suggest that a major reason for the differential sensitivities of the two phenotypes to these drugs is different affinities of their sodium pumps for inhibitors of active transport.

Educational Measurement↗

[Development of an in vitro cardiomyocytes cell model for embryotoxicological and pharmacological studies]

Permanent cell lines of pluripotent embryonic stem cells (ESC) are established from early embryonic stages (blastomeres of 8-cell embryos or blastocysts) of the mouse. We developed an in vitro system for differentiation which allowed the optimal development of ESC into spontaneously pulsating cardiomyocytes. The ESC-derived cardiomyocytes responded to cardioactive substances with heart-specific chronotropic reactions and modifications of the action potentials. The beta-adrenoceptor agonists (-)isoprenaline and clenbuterol, the mediators of the cAMP pathway forskolin and isobutylmethylxanthine as well as the alpha1-adrenoceptor agonist (-)phenylephrine caused positive chronotropic reactions. The muscarinic cholinoceptor agonist carbachol and the L-type Ca2+ channel blockers nisoldipine, diltiazem and gallopamil induced negative chronotropic effects. beta1-, alpha1-adrenoceptors and Ca2+ channels, but no beta2-adrenoceptors are involved in the chronotropic reaction of early developmental states of cardiomyocytes. Terminally differentiatied cardiomyocytes expressed beta2-adrenoceptors and displayed a positive chronotropic response to digitoxin. The contractions of spontaneously pulsating cardiomyocytes were concommitant with rhythmic action potentionals characteristic to those described for embryonic cardiomyocytes and sinusnode cells. The presented ESC-differentiation system may be useful for in vitro studies of cell differentiation and commitment. Furthermore, it may provide an alternative model for pharmacological investigations and for reproductive toxicology thus reducing animal use.

Journal Article↗

Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana.

The alkaloid 13-hydroxylupanine-2-pyrrolcarbonic acid ester (Hoe 933) from the Madagascan plant Cadia ellisiana has an hypotensive and antiarrhythmic effect. The hypotensive effect in dogs, monkeys, and rats anaesthetized with barbiturates reaches its maximum with 0.2 mg/kg i.v. However, the hypotensive effect is much weaker in conscious animals. The enteral absorption in the dog is good; an intraduodenal dose of only 0.5 mg/kg lowered the blood pressure. In the isolated rabbit heart whose accelerator nerves were intact, the perfusion with concentrations of 0.6 mug/min Hoe 933 (total dose 6 mug) decreased the release of norepinephrine from the nerve endings, reduced the positive inotropic effect, and diminished the increase in heart rate produced by electrical stimulation of the accelerator nerve. The effect of the stimulation of the accelerator nerve on dp/dt in dogs in situ was considerably diminished by such low doses as 10 and 25 mug/kg i.v. Consequently, the alkaloid inhibits sympathetic impulse transmission. Sympathetic circulatory reflexes are weakened by the compound. The alkaloid has also a ganglionic blocking effect, which is demonstrated on the upper cervical ganglion of the cat. The effect of preganglionic stimulation of the nictitating membrane was reduced with 200 mug Hoe 933/kg i.v. In the isolated guinea pig heart the effect of nicotine on heart rate and contraction was diminished. In this respect the ganglion blocker pentolinium is 8 times more active. The antifibrillatory effect of Hoe 933 was demonstrated with 0.3 mg/kg i.v. in supercooled cats, the antiarrhythmic activity was evident with 0.5 mg/kg i.v. in dogs intoxicated with K-strophanthin. In isolated hearts of guinea pigs, a dose of only 6 mug/heart inhibited ventricular fibrillation induced by aconitine and digitoxin. Even the toxicity of digoxin was diminished by previous administration of 300 mug/kg i.v. The relative refractory period and the duration of the action potential were prolonged in the isolated papillary muscle of the guinea pig heart.

Alkaloids↗

[Use of cardiac glycosides in chronic circulatory insufficiency].

Features specific for the action produced by the most widely employed cardiac glycosides (strophanthin, corglycon, proscillardin A, methyl- and acetyldigoxine, isolanide, digoxine and digitoxin) on the hemodynamics, peripheral resistance, electrolyte composition, acid-base equilibrium, the blood adenyl system, etc were studied in 375 patients with different stages of chronic circulatory insufficiency. The data thus made available allowed some suggestions to be made as to the choice of cardiac glycosides, the duration of their application, possible combinations thereof, and also to propose a number of measures aimed at preventing the development of poisoning with cardiac glycosides.

Adolescent↗

Specific and high affinity binding of perindoprilat, but not of perindopril to blood ACE.

The bindings of perindopril and of its active metabolite perindoprilat to human serum, isolated proteins and to erythrocytes were studied by equilibrium dialysis. Within the therapeutic concentrations range, perindopril was 74% bound to serum involving a non-saturable process, NKa = 2.87. The main binders are serum albumin and alpha 1-acid glycoprotein. The serum binding of perindoprilat involved two successive steps. First, a saturable high-affinity binding (Ka: 2.8 x 10(9) M-1) occurred, involving probably the angiotensin converting enzyme (ACE). The second binding step was non-saturable with a very weak binding capacity, NKa = 0.15, quite superimposable to the HSA bound perindoprilat. Free fatty acids (FFA) did not alter the binding to HSA. The binding of both compounds to erythrocytes was low especially with perindopril, when measured in the presence of plasma. A significant correlation showed that the overall serum binding percentage of both drugs was essentially determined by HSA concentration. Serum binding was decreased in renal failure or cirrhosis, this result was principally linked to the hypoalbuminemia. Interactions with other drugs were limited to the binding of salicylate, tolbutamide and digitoxin to HSA.

Angiotensin-Converting Enzyme Inhibitors↗

Production and characterization of monoclonal and polyclonal antibodies against digoxin.

Three hybridoma cell lines (DIG 64. 2B. 5, DIG 104. H10.1 and DIG 222. 4D. 5) producing monoclonal antibodies against digoxin were established, and the properties of these monoclonal antibodies were characterized and compared with three polyclonal rabbit anti-digoxin antisera. Both polyclonal and monoclonal antibodies gave association constants ranging from 10(9) to 10(10) (M-1). The monoclonal antibodies were of the IgG1(kappa) or IgG2b(kappa) subclass. Cross-reactivities of these monoclonal antibodies and polyclonal antisera with various related cardenolides and their aglycones were determined by competitive radioimmunoassay. The monoclonal antibodies were specific for digoxigenin-containing glycosides such as lanatoside C and deslanoside, but not for digitoxigenin-containing glycosides. On the other hand, the specificities of the polyclonal antisera were less strict than the monoclonal antibodies and relatively cross-reactive with digitoxin. It was shown that the RIA for digoxin using DIG 64. 2B. 5 is sensitive enough to detect 0.2-0.3 nM (30-60 pg/tube) of digoxigenin-containing cardenolides.

Animals↗

[Ablation of postoperative "incisional" reentrant atrial tachycardia and flutter in children using the CARTO system].

OBJECTIVE: In children with congenital heart diseases who have undergone surgical interventions, postoperative arrhythmias frequently complicate the clinical course. "Incisional" atrial tachycardia or flutter is one of the most common forms of postoperative arrhythmias in these patients and can lead to significant morbidity and even mortality. The aim of this study was to investigate how to use antiarrhythmic drugs and the CARTO system to treat these cases. METHODS: There were 12 patients with "incisional" atrial tachycardia or flutter complicating surgery for congenital heart diseases in this study (3 patients with correction of tetrology of Fallot, 3 with atrial septal defect repair, 2 with ventricular septal defect repair, 1 with switch, 1 with repair of Ebstein's anomaly, 1 with total anomalous pulmonary venous drainage, and 1 with atrial septal closure with the Amplatzer septal occlusion). Patients whose body weight was less than 10 kg or those who did not wish to accept ablation were treated with antiarrhythmic drugs, including digitoxin, propranolol, metoprolol and cordarone. CARTO system was used to map 6 patients whose body weight was more than 10 kg and who agreed with accepting ablation for atrial tachycardia and flutter. Radio-frequency ablation was performed in these 6 cases including two cases of "incisional" atrial tachycardia and 4 of atrial flutter. RESULTS: (1) The antiarrhythmic drug was successful in 6 patients with "incisional" atrial tachycardia. (2) Six patients including 2 children with "incisional" atrial tachycardia and 4 children with atrial flutter were successfully ablated. But one case of "incisional" atrial tachycardia relapsed after 3 months of ablation. This case, however, was successfully ablated again later. No further relapse was observed during the 2 - 24 months of follow-up. CONCLUSION: Ablation of "incisional" atrial tachycardia and flutter is the first choice to treat the patients whose body weight is more than 10 kg and those who agree with accepting ablation by CARTO system. Drug therapy of "incisional" atrial tachycardia and flutter is palliative and it is the only selection to treat the patients whose body weight is less than 10 kg or those who do not wish to accept ablation procedure.

Anti-Arrhythmia Agents↗

Quantitative contribution of endogenous compounds and hypoalbuminemia in reducing the binding of furosemide in the plasma of newborn infants.

The protein binding of furosemide was studied in the plasma of newborn infants and adult subjects. Plasma consisted of two pools obtained from 25 newborns and adult subjects. The concentrations of albumin were 36.8 (newborn) and 48.3 g/l (adult). The unbound fraction of furosemide was 1.38 +/- 0.15 (adult) and 2.03 +/- 0.13% (newborn; p < 0.001). After extensive dialysis of the plasma, the unbound fraction of furosemide was 1.12 +/- 0.15 (adult) and 1.39 +/- 0.09% (newborn; p < 0.0001), suggesting that dialyzable endogenous compounds interfere with the binding of furosemide. The addition of human albumin to the newborn plasma to give a final albumin concentration of 48.3 g/l yielded an unbound fraction of furosemide of 1.63 +/- 0.08 (nondialyzed plasma) and 1.17 +/- 0.08% (dialyzed plasma; p < 0.0001). The addition of albumin to the dialyzed newborn plasma, to give a final albumin concentration similar to that in adult plasma, decreased the unbound furosemide to the level of the dialyzed adult plasma. The binding defect of furosemide in newborn plasma reflects either the effects of the endogenous inhibitors or of hypoalbuminemia. The intrinsic binding properties for furosemide of newborn dialyzed plasma are similar to those of dialyzed adult plasma. This consideration corroborates our previous results on the binding of furosemide and diazepam, salicylic acid and digitoxin to newborn and adult albumin. The displacement of furosemide by salicylic acid, tolbutamide and azapropazone is 70% greater in newborn than in adult plasma. The greater displacing effect is largely due to hypoalbuminemia.

Aging↗

Endogenous digoxin-like immunoreactive factors (DLIF) as measured by the CEDIA digoxin assay and a fluorescence polarization immunoassay.

The sensitivity of a new homogeneous enzyme immunoassay for the determination of digoxin (CEDIA Digoxin assay) and a fluorescence polarization immunoassay (FPIA) to interference by digoxin-like immunoreactive factors (DLIF) was studied in sera from pregnant women, newborns, patients undergoing hemodialysis and patients with renal insufficiency, but without hemodialysis. None of the patients had been treated with digoxin or digitoxin. Cross-reactivity of DLIF in the CEDIA assay was generally lower than in the FPIA. Data on the distribution DLIF of values and method comparisons showed that sera of the four patient groups reacted in a completely different way in both assays, suggesting that the nature of DLIF in the four groups is not identical. Addition of digoxin to sera of patients not treated with this drug resulted in a reduction of the apparent DLIF concentration in the CEDIA assay and the FPIA. This shows that DLIF interference may be less pronounced in sera of patients undergoing digoxin therapy compared to untreated persons. Although the CEDIA assay is less sensitive to DLIF interference than the FPIA, further efforts are needed to reduce the extent of this interference.

Adult↗

Oleandrin-mediated oxidative stress in human melanoma cells.

While certain cardiac glycoside compounds such as oleandrin, bufalin and digitoxin are known to be associated with potent cytotoxicity to human tumor cells, the mechanisms by which this effect is produced are not clear. We now demonstrate that incubation of human malignant melanoma BRO cells with oleandrin results in a time-dependent formation of reactive oxygen species (ROS). Use of Mito-SOX and dihydroethidine dyes revealed the presence of oleandrin-mediated superoxide anions. Formation of superoxide anions correlated with a loss in cellular viability, proliferation and cellular defense mechanisms such as GSH content. Oleandrin also resulted in an unusual time-dependent mitochondrial condensation in BRO cells that could be blocked with use of N-acetyl cysteine (NAC). NAC was also shown to block ROS formation and partially prevent oleandrin-mediated loss of cellular GSH. Taken as a whole, the data suggest that exposure of human tumor cells such as BRO to oleandrin results in the formation of superoxide anion radicals that mediate mitochondrial injury and loss of cellular GSH pools. These mechanisms play a role in cardiac glycoside mediated tumor cell injury. Conversely, incubation of NAC, a precursor to GSH, largely prevents oleandrin-mediated inhibition of proliferation and mitochondria structural changes.

Cardenolides↗

Instability of digoxin in digoxin-amorphous silicon dioxide triturates prepared by solvent deposition and ball milling.

Digoxin underwent hydrolytic degradation to its molecular components when solvent deposited on or ball milled with various commercial grades of amorphous silicon dioxide. The degradation was greater during ball milling than after solvent deposition, and increased with a longer ball milling. By itself digoxin was also degraded by ball milling, but not as much as when a silicon dioxide was present. The extent of the degradation appeared to depend on the acidity, surface area and pore size of the silicon dioxide used. A similar degradative behavior was observed for the related glycoside digitoxin.

Chemistry, Pharmaceutical↗

[Do we use digitalis properly in the management of elderly patients suffering from the signs of chronic heart failure?].

INTRODUCTION: The indications of digoxin therapy has been significantly narrowed and also the effective target therapeutic blood level has been decreased (0.9 micromol/L) compared to the previously desired one. OBJECTIVE: In this retrospective trial the data of 60 consecutive patients over 65 years (25 male, 35 female, mean age 77.3 +/- 5.0 y), hospitalized between 01. 01. 2002 and 31. 12. 2003 with a diagnosis of chronic heart failure and elevated (> 1.2 microg/I) serum level of digoxin, were analyzed. METHODS: Beside the analysis of the age, sex, serum level of digoxin and potassium, creatinine clearance value, symptoms and ECG-signs of digitalis intoxication, presence of atrial fibrillation, concomitant diseases and left ventricular ejection fraction value, the reasonability of digitalis treatment and therapy applied at the time of discharge (considering actual treatment guidelines) were also reviewed. RESULTS: At the admission mean serum level of digoxin was 2.1 +/- 0.9 microg/l. 20 patient's value (33.3%) was found above 2.2 microg/l. Symptoms characteristic for digitalis intoxication were observed in 28 patients. On the ECG performed at admission signs of digitalis effect/overdose were observed in 54 cases ("bigemin" ventricular extrasystoles, bradycardia, characteristic down-sloping ST-depressions). The mean left ventricular ejection fraction of the patients (51.5 +/- 12.7%) did not suggest to a significant left ventricular systolic dysfunction. For the elevated serum level of digoxin the impaired renal function (mean creatinine clearance 42.9 +/- 21.3 mL/min) was responsible in most cases. In patients with the highest serum level of digoxin (n = 20, 3.2 +/- 0.7 microg/L) the creatinine clearance was even lower, 30.4 +/- 13.7 mL/min. During hospital treatment the administration of digitalis was found to be unnecessary and thus terminated in 44 patients. At the discharge only 16 patients were receiving digitalis, 14 of them digoxin and 2 patients digitoxin. CONCLUSIONS: The authors emphasize, that in case of elderly patients the indication and control of digitalis therapy requires greater precaution and tight doctor-patient cooperation.

Aged↗

[Indications for permanent electrosystolic pacing in arrhythmia revealed or aggravated by treatment].

The authors report 25 cases of patients, average age 67 years with severe coronary or valvular heart disease, with conduction disorders. The conduction disorder occurred alone in 8 cases and was associated with a disorder of excitability in 17 cases. It was either obvious, as in 14 cases, or latent, as in 11 cases, and precipitated by various forms of treatment, the disadvantage of which was the negative dromotrope effect. This treatment was prescribed for permanent resting angina (amiodarone and prenylamine), heart failure (digitoxin) or excitability disorder (beta-blockaders or procainamide). 11 patients had one or several fainting attacks. Permanent electro-systolic pacing with stimulation on demand, is necessary in all patients to palliate the consequences of treatment. In 11 cases out of 25, prior temporary pacing permitted the authors to assess the efficacy of treatment. The high post-operative mortality (40%) is not due to the apparatus but depends on the severity of the coronary heart disease or heart failure in these patients, In 60% of cases, the result of stimulation was excellent and was maintained permanently.

Aged↗

[Current treatment protocol in cardiovascular diseases in childhood. 1: Heart failure, diseases in the neonatal period, congenital heart defects. 2: Arrhythmias, carditis, cardiomyopathies, shock, hypertension].

It is given an overview about actual strategies of the treatment of children suffering from heart diseases. Partly proven drugs are given in an optimized doses e.g. digoxin and digitoxin where as other new drugs and therapeutic principles are introduced e. g. catecholamines and vasodilator agents, antiarrhythmic drugs or electrotherapy and antiarrhythmic surgery. Various functional disturbances of the cardiovascular system can occur in the newborn period. New diagnostic principles especially echocardiography with doppler sonography, holter monitoring and exercise testing have lead to better therapeutic regimens. Heart catheterizations have new therapeutic tools like the balloon valvuloplasty of a stenotic pulmonic valve. At least the advances of cardiac surgery have lead to a shift of the time of correction to early childhood. Two step interventions are more and more removed and the related children and their families will have a better outcome and a better life quality.

Arrhythmias, Cardiac↗

Effect of adaptive steroids on the impairment of hepatic drug metabolic activity caused by hepatotoxic agents.

Hepatic disfunction was produced in female rats by ethanol, carbon tetrachloride, dimethyl mercury or Freund's Adjuvant. This disfunction was expressed by increased SGPT, liver triglycerides level, and reduced resistance to zoxazolamine, digitoxin and indomethacin. Treatment with spironolactone, pregnenolone-16_-carbonitrile or triamcinolone reduced only slightly SGPT and triglycerides, but restored the reduced resistance to drugs, and the impairment of the liver drug metabolism in vitro. Triamcinolone was the least effective. Spironolactone, pregnenolone-16_-carbonitrile and triamcinolone were most active in preventing the hepatotoxicity of dimethyl mercury, of carbon tetrachloride and of Freund's Adjuvant respectively. Restoration of drug metabolism is attributed to the microsomal enzyme induction in general. Triamcinolone, when potent in rats with adjuvant induced disease (AID), acted by a glycocorticoid mediated mechanism. In AID, treatment of inflammation restored liver drug metabolism, but restoration of the hepatic drug metabolic activity in AID rats only slightly ameliorated inflammation. None of the tested steroids demonstrated any activity against lipid peroxidation, thus excluding any mediation of a free radical mechanism in spironolactone, PCN or triamcinolone involvement in drug response and metabolism of the damaged liver by the hepatotoxic agents used.

Alanine Transaminase↗

Stimulation of Ca2+ uptake by cyclic AMP and protein kinase in sarcoplasmic reticulum-rich and sarcolemma-rich microsomal fractions from rabbit heart.

The effect of cyclic AMP on Ca2+ uptake by rabbit heart microsomal vesicular fractions representing mainly fragments of either sarcoplasmic reticulum or sarcolemma was investigated in the presence and absence of soluble cardiac protein kinase and with microsomes prephosphorylated by cyclic AMP-dependent protein kinase. The acceleration of oxalate-promoted Ca2+ uptake by fragmented sarcoplasmic reticulum following cyclic AMP-dependent membrane protein phosphorylation, observed by other authors, was confirmed. In addition it was found that the acceleration was greatest at pH 7.2 and almost negligible at pH 6.0 and pH 7.8. A very marked increase in Ca2+ uptake by cyclic AMP-dependent membrane protein phosphorylation was observed in the presence of boric acid, a reversible inhibitor of Ca2+ uptake. In addition to the microsomal fraction thought to represent mainly fragments of the sarcoplasmic reticulum, the effect of protein kinase and cyclic AMP on Ca2+ uptake was investigated in a cardiac sarcolemma-enriched membrane fraction. Ca2+ uptake by sarcolemmal vesicles, unlike Ca2+ uptake by sarcoplasmic reticulum vesicles, was inhibited by low doses of digitoxin. The acceleration of oxalate-promoted Ca2+ uptake by cyclic AMP and soluble cardiac protein kinase, however, was quite similar to what was seen in preparations of fragmented sarcoplasmic reticulum, which suggests that it may reflect an acceleration of active Ca2+ transport across the myocardial cell surface membrane.

Animals↗