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D Escande

Publications and source records attributed to D Escande.

83 records · Page 5Linked to original sources
PubMed1987

Abnormal pacemaking is modulated by sarcoplasmic reticulum in partially-depolarized myocardium from dilated right atria in humans.

Fifty human atrial specimens removed at time of cardiac surgery were studied in vitro. Thirty-four samples were selected as presenting partial cell depolarization and exhibiting slow response action potentials. Twenty of these preparations were automatic whereas 14 were not. Neither mean maximum diastolic potential (-52.8 +/- 1.3 mV and -49.3 +/- 2.2 mV respectively) nor maximum rate of depolarization (Vmax) (1.1 +/- 0.1 V/s and 1.3 +/- 0.8 V/s) significantly differed between these two groups. Abnormal automaticity due to phase 4 depolarization occurred in 12/13 preparations dissected from markedly dilated atria whereas it occurred in only 2/10 preparations sampled from non-dilated atria. A statistically significant relationship between in vitro abnormal pacemaking and atrial dilatations was found. We investigated the effects on abnormal pacemaker depolarization and automaticity of a reduction in the extracellular Na and Ca and of sarcoplasmic reticulum (SR) inhibitors. Abnormal pacemaker depolarization appeared to be much more sensitive to a reduction in the extracellular Na than in the extracellular Ca. Both Sr and Mg slowed the automatic rate. Ryanodine 3 X 10(-6) M, a specific SR inhibitor, irreversibly lengthened the spontaneous basic cycle duration to about 300% of control. Epinephrine up to 10(-4) M was ineffective in accelerating the residual spontaneous rhythm that persists after ryanodine action, although epinephrine markedly enhanced the overshoot and Vmax of the slow responses. It is concluded that, in the human atrial myocardium, abnormal pacemaking that develops at low level of membrane potential: is promoted by chamber dilatation; is strongly modulated by SR-dependent processes.

Adolescent↗
PubMed1987

Effects of quinidine on ventricular repolarization.

The possibility that an asynchronous increase in the ventricular monophasic action potential duration is the basis of the quinidine-induced torsade de pointes, has led us to study the electrophysiological effects of increasing doses of intravenous quinidine. We measured the monophasic action potential duration and the ventricular effective refractory period at several right ventricular myocardial sites in the anaesthetized dog. Our results showed that quinidine induces a dose-dependent prolongation in ventricular effective refractory period and in ventricular monophasic action potential duration. These increases were uniform throughout the right ventricle. No variations in repolarization or in refractoriness were observed between the four ventricular sites studied. The results suggest that quinidine does not have a direct effect on dispersion of repolarization, and that mechanisms other than its direct electrophysiological action are involved in the development of torsade de pointes.

Animals↗
PubMed1987

Two types of transient outward currents in adult human atrial cells.

It has been suggested in a previous article [Escande et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H843-H850, 1985] that transient outward currents may participate in the initial repolarization of human atrial fibers. The present study substantiates the existence of such currents in human myocardium. Membrane currents were recorded in enzymatically dissociated cells using the whole cell patch-clamp technique. Two kinds of transient outward currents were observed: 1) a long-lasting outward current, (ilo), which was suppressed by 4-aminopyridine. The time to peak of ilo was 18.0 +/- 0.7 ms, and its inactivation time constant was 35.7 +/- 2.1 ms at room temperature (test pulses, +20 mV; holding potential, -40 mV); 2) a brief outward current (ibo), which persisted with 3 mM 4-aminopyridine and exhibited a shorter time to peak (5.5 +/- 0.2 ms) and a faster decay (time constant, 9.1 +/- 1.8 ms). ilo was inhibited by Ba but was insensitive to the calcium blocker Co. Co blocked both the slow inward current (isi) and ibo. It is concluded that two different transient outward currents control the repolarization in human atrial cells.

4-Aminopyridine↗
PubMed1986

Characteristics of the time-dependent slow inward current in adult human atrial single myocytes.

The slow inward current isi plays a prominent role in impulse formation and slow conduction in the human heart. For this reason, it may be involved in a great variety of arrhythmias that occur clinically, particularly at the supraventricular level. isi also appears to be the major target of numerous cardioactive drugs daily administered to many patients. Difficulties encountered in voltage clamping human tissues, inevitably dissected from restricted zones of myocardium with inadequate geometry, may explain why direct measurements of this current have never been performed on multicellular human preparations. The recent development of enzymatic techniques allowing the isolation of calcium-tolerant myocytes has provided a solution to these problems. To our knowledge only one abstract has presented until now records of isi in human ventricular myocytes. We describe here the result of experiments carried out to investigate the slow inward current in single cells isolated from adult human atria. The present work provides the first quantitative description of this current in human myocytes.

Atrial Function↗
PubMed1985

Age-related changes of action potential plateau shape in isolated human atrial fibers.

Because the frequency of atrial arrhythmia increases dramatically with age in humans, we investigated age-related changes of cellular electrical activity in human atrial fibers, utilizing standard microelectrode techniques. Twenty-four atrial samples, uniformly exhibiting fast responses, were selected. Patients were in two different age groups: 10.0 +/- 7.0 mo and 54.4 +/- 9.7 yr. Although mean maximum diastolic electrical potential did not significantly differ, the two groups showed marked dissimilarities in action potential (AP) shape. Adult-type APs always exhibited an initial notch followed by a low-level prolonged plateau, whereas APs of the young were more triangular and had a short plateau approaching zero potential. 4-Aminopyridine (0.5 mM) markedly increased the level of the adult AP plateau without suppressing the initial notch, which disappeared after further addition of caffeine (10 mM). The simultaneous action of the two drugs changed an adult-type AP into a young type. The drug effects were much less marked in young atria. Our results suggest that an age-related increase in transient outward currents can account for the differences in plateau shape described. Moreover, age-related differences in plateau configuration in response to a period of rest suggest a faster repriming kinetic of these currents in adults.

4-Aminopyridine↗
PubMed1985

[Cellular electrophysiology of abnormal automaticity foci].

Foci of abnormal automaticity are the result of either 1) an abnormal pacemaker discharging spontaneously in the absence of an initiating stimulation usually arising in the midst of depolarised myocardial fibres but also from zones of physiological subsidiary automaticity normally inhibited during sinus rhythm, or 2) automatic activity triggered by an initiating stimulus related to oscillating after-depolarisation or early after-depolarisation. Oscillating after-depolarisation, the clinical expression of which was thought initially to be limited to digitalis toxicity, can arise in any experimental situation associated with calcium overload of the cell. Early after-depolarisation which often occurs during the terminal phase of the action potential of the Purkinje fibres, arises under different experimental conditions to those giving rise to oscillating after-depolarisation. Cellular electrophysiological techniques demonstrate the mechanism responsible for abnormal automaticity and the sites of action of antiarrhythmic drugs. Close collaboration between cellular electrophysiologists and clinicians is necessary to establish the responsibility of mechanisms demonstrated in vitro in the genesis of clinical arrhythmias.

Action Potentials↗
PubMed1985

[The variability in the duration of human atrial action potentials increases with age].

35 human atrial samples, presenting electrophysiological characteristics within "normal" limits, were studied in vitro. 19 were sampled from adult patients and 16 were sampled from very young patients. Maximum diastolic potential did not significantly differ between adult and young, either in mean value or in variability. Action potential duration increased with age, particularly during the earliest years of life. The variability of action potential duration, which is considered as an arrhythmogenic factor, is greater in the adult.

Action Potentials↗
PubMedDate not supplied

Ca2+-sensitive cytosolic nucleases prevent efficient delivery to the nucleus of injected plasmids.

BACKGROUND: Efficient gene delivery by synthetic vectors is a major challenge in gene therapy. However, inefficient nuclear delivery of cDNA is thought to be a major limiting step in gene transfer using non-viral vectors. It is commonly thought that, in the cytosol, cDNA has to be released from its vector before importation to the nucleus. The stability of naked cDNA in the cytoplasm is not well established. METHODS: cDNA plasmids, either free or complexed with poly(ethyleneimine) (PEI), were microinjected into the cytoplasm of mammalian cells and their turnover was assessed by fluorescence in situ hybridization (FISH). Incubations of cDNA plasmids in cytosolic extracts were also performed. RESULTS: FISH experiments showed that naked cDNA rapidly fade with time when injected into the cytosol. Fading was not observed when naked cDNA plasmids were injected into the nucleus. Incubation of naked cDNA in a cytosolic fraction isolated from mammalian cells reproduced cDNA degradation as observed in microinjection experiments. Nuclease inhibitors, including aurin tricarboxylic acid or Zn2+, prevented in vitro cDNA degradation. The cytosolic nuclease activity was optimal at physiological pH and physiological Ca2+ concentration. By contrast, it was insensitive to Mg2+ or Na+ concentrations. Finally, cDNA complexation with PEI or addition of oligonucleotides prevented in vitro cDNA degradation. CONCLUSION: Altogether, these experiments suggest that cDNA digestion by cytosolic nucleases occur when the decomplexed transgene is present in the cytosol. We propose that the inefficient transfer of cDNA into the nucleus during transfection with synthetic vectors may result from rapid digestion of naked cDNA by a Ca2+-sensitive cytosolic nuclease.

Animals↗
PubMedDate not supplied

Effects of potassium conductance inhibitors on spontaneous diastolic depolarization and abnormal automaticity in human atrial fibers.

The capability of generating spontaneous diastolic depolarization and automaticity was investigated in vitro by means of standard microelectrode techniques in 50 human atrial preparations. Samples were classified within two groups: group 1 was composed of 12 well-polarized preparations exhibiting action potentials that were fast responses (mean maximum diastolic potential: -75.5 mV and Vmax greater than 100 V/s); group 2 was composed of 38 partially-depolarized samples (mean maximum diastolic potential: -50.3 mV and Vmax less than 10 V/s) and was further divided into two subgroups. Subgroup 2A consisted of 20 spontaneously beating preparations and subgroup 2B consisted of 18 non-automatic partially-depolarized specimens. Highly-polarized fibers from group 1, although exhibiting a slight diastolic depolarization which was almost entirely suppressed by 2 mM caesium, never presented spontaneous activity under our experimental conditions. 90% of automatic fibers from subgroup 2A were sampled from dilated atria. In automatic preparations, diastolic depolarization was usually separated into two phases: an initial phase, also present in non-automatic fibers, and a late phase. Changes in the initial phase were not accompanied by concomitant changes in the spontaneous rate. Abnormal automaticity was clearly related to the late diastolic phase (absent in non-automatic fibers), the generation of which appeared to be a specific property of automatic fibers. The use of K conductance inhibitors (caesium, 4-aminopyridine, barium, low K solutions) provided indirect evidence that neither delayed outward ix current nor if type inward current are principally responsible for abnormal automaticity.

4-Aminopyridine↗