-
Journal of Molecular and Cellular... Nov 1987Delayed afterdepolarizations and triggered activity occur in atrial cells of the canine coronary sinus in response to catecholamines. We studied the properties of the...
Delayed afterdepolarizations and triggered activity occur in atrial cells of the canine coronary sinus in response to catecholamines. We studied the properties of the membrane current that causes the afterdepolarizations with the two-microelectrode voltage clamp technique in small preparations (about 0.5 x 1 mm). At a holding potential of -50 mV a transient inward current (TI) occurred after repolarization from a depolarizing step to between -40 and -20 mV in the absence of catecholamines. When the depolarizing pulse was made more positive or its duration increased the amplitude of the TI current increased and it reached peak amplitude faster. The current-voltage relationship of the TI current was studied by changing the voltage to which the membrane was repolarized after a depolarizing clamp pulse of fixed amplitude and duration. At repolarization levels positive to -30 mV there were current fluctuations without a distinct TI current. As the repolarization voltage was made more negative, a TI current occurred and its time to peak increased monotonically. The TI current amplitude increased and reached a maximum amplitude at around -60 to -70 mV, and then declined at more negative repolarization voltages. Norepinephrine increased the TI current while simultaneously augmenting the slow inward current. Elevating [Ca]0 increased the TI current amplitude. Caffeine (2 mM) increased the TI current amplitude, while caffeine (4 mM) increased and then decreased the current amplitude. The dependence of the TI current on the voltage and duration of the activating depolarizing step in these atrial cells are qualitatively similar to those of the TI current associated with digitalis toxicity in Purkinje fibers and ventricular muscle, although there are some quantitative differences. There is no distinct TI reversal in these atrial cells, similar to TI in ventricular muscle but dissimilar to TI in Purkinje fibers.
Topics: Animals; Atrial Function; Caffeine; Calcium Chloride; Dogs; Heart; Heart Atria; In Vitro Techniques; Membrane Potentials; Norepinephrine
PubMed: 3437461
DOI: 10.1016/s0022-2828(87)80354-1 -
Anesthesiology Aug 1991Atrial tachyarrhythmias are a common manifestation of digitalis toxicity. Such arrhythmias could be due to enhanced automaticity of subsidiary atrial pacemakers (SAP)...
Anesthetics and automaticity in latent pacemaker fibers. III. Effects of halothane and ouabain on automaticity of the SA node and subsidiary atrial pacemakers in the canine heart.
Atrial tachyarrhythmias are a common manifestation of digitalis toxicity. Such arrhythmias could be due to enhanced automaticity of subsidiary atrial pacemakers (SAP) compared to the sinoatrial (SA) node. Halothane is known to oppose digitalis-induced ventricular arrhythmias. Its effect on digitalis-caused atrial arrhythmias is unknown. Therefore, we tested two hypotheses, as follows. First, increasing ouabain concentrations would enhance automaticity of SAP compared to the SA node and that such enhanced automaticity could explain digitalis-caused atrial tachyarrhythmias. Second, halothane would oppose such enhanced automaticity of SAP, thereby opposing digitalis-caused atrial tachyarrhythmias. A canine right atrial preparation was perfused via the SA node artery with Krebs' solution (36.0 +/- 0.5 degrees C) equilibrated with 97% oxygen-3% carbon dioxide. Four bipolar extracellular electrodes recorded the site of earliest activation (SEA), which in this preparation could be the SA node or increasingly remote sites of SAP approximately 1, 2, and 3 cm distal to the SA node along the sulcus terminalis. Pacemaker shifts to SAP during exposure to drugs were scored for magnitude of shift as 1, 2, or 3 depending on which SAP site was the SEA. Magnitude scores were summed for each test condition and normalized by dividing the total number of preparations tested. Preparations (n = 48) were exposed to 1 or 2% halothane (perfusate concentrations of 0.51 +/- 0.01 or 0.79 +/- 0.03 mM, respectively) and/or to low- or mid-therapeutic (2.5 or 5 x 10(-8) M) or borderline toxic ouabain (1 x 10(-7) M). Normalized magnitude scores were not significantly different from zero (control value) with any halothane or ouabain concentration alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Dogs; Dose-Response Relationship, Drug; Drug Combinations; Electrophysiology; Female; Halothane; Heart Conduction System; Heart Rate; Male; Ouabain; Sinoatrial Node
PubMed: 1859018
DOI: 10.1097/00000542-199108000-00019 -
British Journal of Pharmacology and... Sep 1957Movements of potassium have been observed in isolated right and left auricles of rabbits by means of radioactive tracer. The tissues have been immersed in a modified...
Movements of potassium have been observed in isolated right and left auricles of rabbits by means of radioactive tracer. The tissues have been immersed in a modified Krebs saline at 37 degrees , and in these conditions showed only small changes in ionic content over periods up to 6 hr. The extracellular volume, determined with inulin and with (24)Na, was large (44.1 ml./100 g. tissue), and accounted for about 3.8% of the tissue potassium. Left auricles exchanged without gross inhomogeneity: the rate of exchange was about 1.5% of the total tissue potassium/min., though it was probably higher in the first half-hour or hour after preparation. In right auricles the exchange was less homogeneous and included a faster component than that observed in left auricles. Digoxin and ouabain reduced the influx and had no appreciable effect on the efflux of potassium, so that the auricles lost potassium. The threshold concentrations which produced effects within 20 min. were of the order of 10(-6) for ouabain and somewhat higher for digoxin. Irregularities or failure of contraction occurred when the tissue potassium was reduced by about 15%. Loss of potassium was accompanied by gain of sodium, but the tissue appeared unsuitable for making estimations of the rate of sodium movement.
Topics: Animals; Digitalis; Digitalis Glycosides; Digoxin; Myocardium; Ouabain; Potassium; Rabbits; Sodium; Strophanthins
PubMed: 13460247
DOI: 10.1111/j.1476-5381.1957.tb00151.x -
California State Journal of Medicine Jun 1904
PubMed: 18733124
DOI: No ID Found -
Biophysical Journal Jun 1982Spontaneous oscillatory fluctuations in membrane potential are often observed in heart cells, but their basis remains controversial. Such activity is enhanced in cardiac...
Spontaneous oscillatory fluctuations in membrane potential are often observed in heart cells, but their basis remains controversial. Such activity is enhanced in cardiac Purkinje fibers by exposure to digitalis or K-free solutions. Under these conditions, we find that voltage noise is generated by current fluctuations that persist when membrane potential is voltage clamped. Power spectra of current signals are not made up of single time-constant components, as expected from gating of independent channels, but are dominated by resonant characteristics between 0.5 and 2 HZ. Our evidence suggests that the periodicity arises from oscillatory variations in intracellular free Ca that control ion movements across the surface membrane. The current fluctuations are strongly cross-correlated with oscillatory fluctuations in contractile force, and are inhibited by removing extracellular Ca or exposure to D600. Chelating intracellular Ca with injected EGTA also abolishes the current fluctuations. The oscillatory mechanism may involve cycles of Ca (or Sr) movement between sarcoplasmic reticulum and myoplasm, as previously suggested for skinned cardiac preparations. Our experiments in intact cells indicate that changes in surface membrane potential can modulate cytoplasmic Ca oscillations in frequency and perhaps amplitude as well. A two-way interaction between surface membrane potential and intracellular Ca stores may be a common feature of heart, neuron, and other cell types.
Topics: Animals; Calcium; Cattle; Egtazic Acid; Evoked Potentials; Heart Conduction System; Membrane Potentials; Myocardial Contraction; Purkinje Fibers; Strontium
PubMed: 6809065
DOI: 10.1016/S0006-3495(82)84557-8 -
Clinical Cardiology Oct 1994K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated cardiomyopathy and sinus rhythm. K-strophanthin (0.125 mg intravenously) or digoxin (0.25 mg orally) were administered daily in two 3-month periods, during which vasodilators and diuretics were kept constant and patients received one of the two digitalis preparations in a double-blind fashion, crossing over to the alternative preparation in the next period. Blindness was assured throughout the trial with a daily intravenous injection of 10 ml normal saline solution either containing K-strophanthin or not, and with daily oral administration of either placebo or active digoxin. At the end of the run-in period, 15 days after starting active preparations, and thereafter every month for the next 6 months, we evaluated left ventricular pump function at rest and patients' functional performance by a cardiopulmonary exercise test. At Day 15, cardiac index and ejection fraction at rest, compared with run-in, were significantly raised with both glycosides; during exercise while on K-strophanthin, peak oxygen consumption was augmented by 1.4 ml/min/kg (p < 0.01) and oxygen consumption at anaerobic threshold by 2.2 ml/min/kg (p < 0.01); corresponding variations on digoxin (-0.1 and +0.3, respectively) were not significant versus run-in. These patterns were duplicated at repeated tests during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Anaerobic Threshold; Analysis of Variance; Cardiomyopathy, Dilated; Digoxin; Double-Blind Method; Drug Administration Schedule; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Stroke Volume; Strophanthins; Ventricular Function, Left
PubMed: 8001300
DOI: 10.1002/clc.4960171005 -
The Journal of Biological Chemistry Oct 1980Three derivatives of ouabain have been synthesized which alkylate the digitalis receptor. These derivatives were formed through reductive amination of...
Three derivatives of ouabain have been synthesized which alkylate the digitalis receptor. These derivatives were formed through reductive amination of p-nitrophenyltriazene (NPT) ethylenediamine to the periodate-oxidized rhamnose moiety of ouabain. The non-covalent binding of the ouabain derivatives (NPT-ouabain, designated I, II, and III) was followed (i) by their ability to inhibit the activity of sodium- and potassium-activated ATPase ((Na+,K+)-ATPase) purified from the electric organ of Electrophorus electricus, (ii) by the binding of [3H]NPT-ouabain I to the enzyme, and (iii) by the inhibition of [3H]ouabain binding with unlabeled NPT-ouabain I. Covalent modification of the digitalis site of (Na+,K+)-ATPase occurs after long periods of time. At pH 7.5 (25 degrees C) the best alkylating derivative, NPT-ouabain I, gives maximum covalent labeling after 6 h. Only the large polypeptide chain (Mr = 93,000) of the purified enzyme is specifically labeled with [3H]NPT-ouabain I while the glycoprotein chain (Mr = 47,000) is not significantly labeled. Labeling of a microsomal fraction of the electric organ with [3H]NPT-ouabain I gave the same type of gel pattern as that observed with the purified enzyme. [3H]NPT-ouabain I was also used to label the digitalis receptor in highly purified axonal membranes and in cardiac membranes prepared from embryonic chick heart. Although the (Na+,K+)-ATPase in both types of membranes has a low affinity for ouabain, [3H]NPT-ouabain I proved to be a very efficient affinity label for the digitalis receptor. In the complex mixture of polypeptides found in these membrane preparations, only a single polypeptide chain having a Mr = 93,000 is specifically labeled by [3H]NPT-ouabain I.
Topics: Affinity Labels; Alkylating Agents; Animals; Electric Organ; Electrophorus; Kinetics; Ouabain; Receptors, Drug; Sodium-Potassium-Exchanging ATPase; Spectrophotometry, Ultraviolet; Triazenes
PubMed: 6253459
DOI: No ID Found -
California Medicine Mar 1958Congestive failure in infants and children is not uncommon and may be present in a varying number of conditions, particularly in certain types of congenital heart...
Congestive failure in infants and children is not uncommon and may be present in a varying number of conditions, particularly in certain types of congenital heart disease. Its recognition and proper treatment are usually followed by improvement, except in those instances where the failure is associated with a lesion incompatible with life. The essentials of treatment are: Treatment of the underlying cause, administration of a digitalis preparation, low salt diet, diuretics, rest and sedation, oxygen, adequate diet and, in rare instances, the use of steroids.
Topics: Child; Diet, Sodium-Restricted; Digitalis Glycosides; Diuretics; Heart Defects, Congenital; Heart Failure; Humans; Infant; Rest; Steroids
PubMed: 13511210
DOI: No ID Found -
The effect of digoxin on the right ventricular pressure in hypertensive and ischaemic heart failure.British Heart Journal Oct 1950
Topics: Blood Pressure; Blood Pressure Determination; Digitalis; Digitalis Glycosides; Digoxin; Heart; Heart Failure; Hedera; Hypertension; Ventricular Pressure
PubMed: 14777836
DOI: 10.1136/hrt.12.4.317 -
The Journal of Physiology Aug 19821. Effects of digitalis compounds on slow inward Ca current I(si)) and contractile force were examined in ferret ventricular muscle (single sucrose-gap voltage clamp)...
1. Effects of digitalis compounds on slow inward Ca current I(si)) and contractile force were examined in ferret ventricular muscle (single sucrose-gap voltage clamp) and calf Purkinje fibres (two micro-electrode voltage clamp).2. In ventricular muscle, ouabain increased I(si) and inward current tails associated with I(si) conductance. The enhancement of I(si) followed a time course similar to the development of the positive inotropic effect, and it could be observed in the absence of aftercontractions or other signs of toxicit.3. The response of myocardial I(si) and twitch force to ouabain depended strongly on a previous history of driven action potentials.4. Veratridine, a toxin that promotes Na entry through tetrodotoxin-sensitive channels, also increased I(si) and twitch force in driven ventricular muscle preparations.5. The effects of ouabain, action potential stimulation and veratridine are consistent with reported effects of K-poor solutions in indicating that elevation of intracellular Na can lead to enhancement of I(si). Additional experiments suggest that the link between Na(i) and I(si) involves intracellular Ca.6. When Cs-loaded Purkinje fibres were bathed in solutions containing Sr instead of Ca, enhancement of I(si) by strophanthidin was abolished even though a positive inotropic response persisted.7. After intracellular injection of Purkinje fibres with EGTA, I(si) no longer increased with strophanthidin, although it remained responsive to adrenaline.8. Clear-cut increases in I(si) were seen in Cs-loaded Purkinje fibres even at very low concentrations of strophanthidin (20-50 nM), where the occurence of Na pump inhibition has been questioned.9. Positive regulation of Ca entry by intracellular Ca may act as a facilitory mechanism that amplifies myocardial responsiveness to digitalis and other inotropic interventions. Through changes in I(si), small rises in diastolic free Ca might lead to large increases in the activator Ca transient during contraction.
Topics: Animals; Calcium; Cattle; Digitalis Glycosides; Dose-Response Relationship, Drug; Feedback; Ferrets; In Vitro Techniques; Ion Channels; Membrane Potentials; Myocardial Contraction; Ouabain; Purkinje Fibers; Sodium; Veratridine
PubMed: 6292410
DOI: 10.1113/jphysiol.1982.sp014321