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Biomedical subjects

Y Palti

Publications and source records attributed to Y Palti.

13 recordsLinked to original sources
PubMed1992

Prediction of immediate ventricular arrhythmias after coronary artery ligation.

OBJECTIVES: Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability. BACKGROUND: Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG. METHODS: With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated. RESULTS: Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1 +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/- 2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex. CONCLUSIONS: Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation.

Analysis of Variance↗
PubMed1992

Intercellular conduction velocity variability as the basis for re-entrant arrhythmias in the ischemic myocardium.

Re-entrant arrhythmias are the major cause of death from cardiovascular disease. A number of models or mechanisms have been proposed to explain the generation of re-entrant arrhythmias in the ischemic or damaged heart. However, none of these models can qualitatively predict the formation of re-entry movements with no modifications of the basic electrophysiologic characteristics of the myocardium. In this presentation we evaluate the concept that the generation of re-entrant arrhythmias is due to increased variance in the conduction characteristics of the cardiac tissue, rather than to modification of these properties. Using a model of a homogeneous two-dimensional matrix of excitable conducting cells, we derived the relationship between the relative standard deviation (RSD) and the probability of occurrence of a local ordered dispersion of velocities shown to have the potential to result in circular propagation. This probability was found to be insignificant when the RSD was lower than 10%, but increased dramatically for RSDs greater than 10%. On the basis of experimental RSD, the calculated probability for circus movement formation is one in 10,000 normal heart beats and one in two ischemic heart beats. The model provides new insight into the mechanism of re-entrant arrhythmias as well as new tools for diagnosis.

Arrhythmias, Cardiac↗
PubMed1992

Involvement of different S4 parts in the voltage dependency of Na channel gating.

Three synthetic peptides corresponding to parts of S4 of the first repeat of eel electroplax sodium channel were synthesized. The basic peptide was C1+ which corresponds to amino acids 210-223 (eel channel numbering) and two subfractions: an external fraction, C1+ex (amino acid 210-217); and an internal part, C1+in (amino acid 218-221). Peptide C1+ includes four of the charged amino acids of this domain; peptide C1+ex includes three of the charged amino acids and is closer to the external membrane surface (according to channel models) than peptide C1+in which includes the fourth charged amino acid alone. Antibodies generated in rabbits against these peptides were shown to be site specific. Using the whole-cell patch-clamp technique, we found that in rat dorsal root ganglion (DRG) cells, the antibodies against C1+in but not against C1+ex had an effect on the gating parameters. They shifted the Na-channel inactivation curve towards hyperpolarization and decreased the slope of the Na-channel activation curve. These results demonstrate that during the conformational changes associated with channel gating, the fourth charged amino acid of S4 must be accessible to antibodies given to the external solution. Furthermore, they indicate a specific involvement of S4 in the voltage dependency of the gating processes.

Amino Acid Sequence↗
PubMed1992

Mechanism of hyperthyroidism-induced modulation of the L-type Ca2+ current in guinea pig ventricular myocytes.

The positive inotropic effects of thyroid hormone in the heart, increased force and velocity of contraction have been mostly attributed to modulation of myosin ATPase isoenzymes (V1, V2 and V3), and sarcoplasmic reticulum Ca2+ pumping activity. In addition, we have suggested that the effects on ventricular contraction result from a thyroid hormone-induced increase in L-type Ca2+ current (ICa,L). Due to the central role of ICa,L in excitation-contraction coupling, we studied mechanisms whereby thyroid hormone augments this current. Since thyroid hormone modulates adenylate cyclase activity in various tissues, we tested the hypothesis that the hormone activates adenylate cyclase, leading to increased cyclic adenosine monophosphate (cAMP) levels, protein kinase A activation, Ca2+ channel phosphorylation and increased ICa,L. We therefore stimulated or inhibited different sites along the "adenylate cyclase cascade", and measured ICa,L and isometric twitch in ventricular myocytes and papillary muscles from euthyroid and hyperthyroid guinea pigs. Our major findings were as follows. In euthyroid myocytes, 0.1 microM isoproterenol (Iso) increased ICa,L (at VM = 0 mV) from -7.04 +/- 0.72 to -22.26 +/- 1.88 pA/pF, P < 0.05, while in hyperthyroid myocytes (ICa,L = -21.48 +/- 2.94 pA/pF), Iso was ineffective. In euthyroid myocytes, intracellular application of cAMP (50 microM) was as potent as Iso, but ineffective in hyperthyroid myocytes. In hyperthyroid myocytes, a protein kinase A inhibitor (2 microM) lowered ICa,L from -26.82 +/- 1.54 to -10.17 +/- 1.70 pApF (P < 0.05), but had no effect in euthyroid myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Beat-to-beat electrocardiographic morphology variation in healed myocardial infarction.

Using high-fidelity electrocardiographic (ECG) amplifiers, we measured subtle beat-to-beat ECG morphologic variations at different phases of the ECG complex. The electrocardiograms were recorded from 49 men with a documented Q-wave myocardial infarction and from 30 age-matched normal men. Forty consecutive beats were averaged to achieve an average ECG signal from which variance could be calculated. The relative variance, defined as the ratio between the integrated variance of the examined window and the integrated variance of the ECG signal that was close to full cycle length, was calculated at QRS onset and at offset in 2 frequency bands (4 to 40 and 60 to 120 Hz). Patients with healed infarction had a relative variance of 2.1 +/- 0.5 (mean +/- standard deviation [SD]) at QRS offset (a window of 40 ms), which was significantly lower than that of the healthy volunteers: 2.5 +/- 0.33 (mean +/- SD; p less than 0.02) at the low-frequency band. At the high-frequency band, patients with healed infarction had a significantly higher relative variance than the control subjects at QRS onset: 1.95 +/- 0.58 vs 1.55 +/- 0.35 (mean +/- SD; p less than 0.005). A model based on the numerous minor conduction abnormalities that exist in the chronically ischemic myocardium is presented to explain the changes in variance at the onset and offset of the QRS. The variance changes described can eventually serve as quantitative indexes of myocardial injury and electrical stability in patients with ischemic heart disease.

Aged↗
PubMed1991

Potassium channel block by internal calcium and strontium.

We show that intracellular Ca blocks current flow through open K channels in squid giant fiber lobe neurons. The block has similarities to internal Sr block of K channels in squid axons, which we have reexamined. Both ions must cross a high energy barrier to enter the blocking site from the inside, and block occurs only with millimolar concentrations and with strong depolarization. With Sr (axon) or Ca (neuron) inside, IK is normal in time course for voltages less than about +50 mV; but for large steps, above +90 mV, there is a rapid time-dependent block or "inactivation." From roughly +70 to +90 mV (depending on concentration) the current has a complex time course that may be related to K accumulation near the membrane's outer surface. Block can be deepened by either increasing the concentration or the voltage. Electrical distance measurements suggest that the blocking ion moves to a site deep in the channel, possibly near the outer end. Block by internal Ca can be prevented by putting 10 mM Rb in the external solution. Recovery from block after a strong depolarization occurs quickly at +30 mV, with a time course that is about the same as that of normal K channel activation at this voltage. 20 mM Mg in neurons had no discernible blocking effect. The experiments raise questions regarding the relation of block to normal channel gating. It is speculated that when the channel is normally closed, the "blocking" site is occupied by a Ca ion that comes from the external medium.

Animals↗
PubMed1979

Diffusion of ions in myelinated nerve fibers.

The diffusion of ions towards or away from the inner side of the nodal membrane in preparations, the cut ends of which are placed in various media, was investigated. The ion concentration changes were calculated by numerical solution of the unidimensional electrodiffusion equation under a variety of media compositions, axoplasmic diffusion coefficients, and internal anionic compositions. The potassium and cesium ion diffusion along the axon towards the node was determined experimentally by two different electrophysiological methods. On the basis of comparison between the experimental data and the computational predictions the axoplasmic potassium ion diffusion coefficient was determined to be almost equal to that in free aqueous solution, while that of cesium ion was close to one half of that in aqueous solution. Utilizing the values of diffusion parameters thus determined, we solved the electrodiffusion equation for a number of common experimental procedures. We found that in short fibers, cut 0.1-0.2 cm at each side of the node, the concentration approached values close to the new steady-state values within 5-30 min. In long fibers (over 1 cm long) steady-state concentrations were obtained only after a few hours. Under some conditions the internal concentrations transiently overshot the steady-state values. The diffusion potentials generated in the system were also evaluated. The ion concentration changes and generation of diffusion potential cannot be prevented by using side pools with cation content identical to that of the axoplasm.

Animals↗
PubMed1978

Cole-Moore effect in the frog node.

Potassium currents were recorded from the voltage-clamped frog node (Rana esculenta) during various test pulses that followed hyperpolarizing prepulses of different amplitudes and durations. Both the delay in potassium current onset and the shape of the current trace as a function of time were found to be a function of prepulse parameters. This finding is different from the current trace superposition described by Cole and Moore for a specific test pulse, sodium equilibrium potential in the squid giant axon. The Cole-Moore effect, which was found here only under a specific set of conditions, thus may be a special case rather than the general property of the membrane. The implication of these findings to the various excitable membrane potassium channel models, which are based on the Cole-Moore effect, is discussed.

Animals↗
PubMed1976

Effect of conditioning potential on potassium current kinetics in the frog node.

The kinetics of potassium conductance changes were determined in the voltage clamped frog node (Rana esculenta), as a function of conditioning prepotential. The conditioning potential duration varied from 1 to 50 ms and the amplitude between -60 and +130 mV (relative to rest). The conductance kinetics were determined at a single test potential of +20 mV (depolarization) by means of the slope of log [ninfinity - nt] vs. time relationship which defines the time constant of the process (tau). The values of tau, after conditioning hyperpolarizations, were around 5 ms, up to 10 times greater than values obtained following a strong depolarization. The tau vs. pre-potential curve was sigmoid in shape. These differences were only slightly dependent on [K+]0 or conditioning pulse duration. The steady-state current values were also found to be a function of conditioning potential. After conditioning hyperpolarizations, the log [ninfinity - nt] vs. time curve could not be fitted by a single exponent regardless of the power of n chosen. The prepotential dependency of potassium current kinetics is inconsistent with the Hodgkin-Huxley axon model where the conductance parameters are assumed to be in either one of two possible states, and where the rate of transfer from one state to the other follows first order kinetics. In contrast the described kinetics may be consistent with complex multistate potassium "channel" models or membranes consisting of a number of types of channels.

Animals↗
PubMed1975

Ionic dependence of sodium currents in squid axons analyzed in terms of specific ion "channel" interactions.

Inward sodium currents were measured from voltage-clamped giant axons externally perfused with artificial seawater (ASW) solutions containing various concentrations of sodium and potassium ions. The data was analyzed under the assumption that under a constant membrane potential sodium conductance is determined by a specific ion-channel site (SIS) reaction. The sodium current density values were expressed in terms of SIS-reaction rates which were compared, by means of minimization techniques, with those computed for various saturation reaction mechanisms. The following conclusions were drawn: 1) The dependence of peak inward sodium current on external sodium and potassium concentrations can be described in terms of saturation reactions. 2) The experimental data fit well the kinetics of a positive cooperative homotropic reaction, involving at least two allosteric active sites. One of these sites may be catalytic while the other, either catalytic or regulatory. 3) The inhibitory effect of external potassium on inward sodium current, can be described by a reversible competitive or noncompetitive inhibition mechanism. The values of the dissociation constant of the inhibitor-site "complex" (Ki) were found to be close to the external potassium concentration under physiological conditions.

Animals↗
PubMed1975

Dipole moment, enthalpy, and entropy changes of Hodgkin-Huxley type kinetic units.

Dipole moment, enthalpy, and entropy changes were calculated for hypothetical structural units which control the opening and closing of ionic channels in axon membranes. The changes of these thermodynamic functions were calculated both for activation (transition to intermediate complex) and for the structural transformation as a whole. The calculations are based on the experimentally determined Q10 values and the empirical formulae for the rate constants (alpha's and beta's) as functions of membrane potentials in Hodgkin-Huxley type models. From the calculated thermodynamic functions we suggest that the specific structural units of the axon membranes are probably of macromolecular (possible protein-like) dimensions with large dipole moments (hundreds of debyes). The calculated dipole moment changes of a single structural unit indicate that in many cases these dipole moments saturate at strong depolarizations or hyperpolarizations. The transitions in structural units show substantial activation enthalpies and entropies but the net enthalpy and entropy changes are practically negligible for the transition as a whole, i.e. the structural units presumably undergo displacements. While the calculated dipole moment changes associated with structural transformations in Loligo and Myxicola show similar potential dependencies, those for Rana usually show a different behavior. The relevance of the dipole moment changes to gating currents is discussed.

Animals↗
PubMed1975

Computation of axon gating currents from dipole moment changes in channel subunits.

The gating polarizational currents were computed on the basis of the dipole moment changes occurring in nerve membrane ionic channel subunits. Membrane thickness and surface density of channels were the only parameters used in addition to the Hodgkin-Huxley model. The gating currents computed for membrane potentials where the Hodgkin-Huxley empirical formulae are reliable were found to be in good agreement with the available experimental data. It is demonstrated that the gating currents of the n and h subunits are responsible for the late slowly decaying gating currents.

Animals↗