Josef Šumbera

Electromechanical correlations in the mammalian heart muscle

SummaryThe relationship between contractility and the duration of the action potential (AP) was examined on sheep trabeculae, employing the sucrose gap technique in order to control the duration of AP, and on guinea pig papillary muscles under conditions which alter both the AP configuration and the contractile response. Three significant types of electromechanical correlation were proved:A.The time to peak tension—or more generally the time to the onset of terminal relaxation—closely follows the duration of AP. The level of the membrane potential, at which contraction turns into relaxation is variable, very likely depending on the intracellular concentration of Ca.B.A linear relation was ascertained between the duration of a single prolonged AP or the sum of duration of APs in an interpolated volley of extrasystoles, and total extra tension developed in all augmented contractions. This relation probably reflects loading of the coupling mechanism by activator Ca.C.A steady relation was found between the positive inotropic effect of increased frequency or concentration of Ca in the medium, of decreased temperature and of a prolonged AP on the one hand, and a concurrent increase of the rate of repolarization on the other. It is assumed that this relation represents a parallel effect of Ca on the contractile machine and on movements of other ions across the membrane (probably increased K efflux). It is suggested that this characteristics may play the role of a negative feed back mechanism. The described correlations are constantly reproducible and statistically significant.ZusammenfassungDie Beziehung zwischen Kontraktilität und Aktionspotentialdauer wurde mit zwei verschiedenen experimentellen Ansätzen verfolgt: einmal mit Trabekeln vom Schaf, bei denen durch die „sucrose gap”-Methode die Dauer des AP kontrolliert werden konnte, einmal an Papillarmuskeln von Meerschweinchen, unter solchen Versuchsbedingungen, bei denen sich die Konfiguration des AP und die mechanische Antwort ändern. Es wurden drei bedeutende Korrelationstypen festgestellt:A.Die Gipfelzeit, oder allgemeiner, die Zeit bis zu dem Anfang der terminalen Erschlaffung ist eng mit der Dauer des AP korreliert. Die Höhe des Potentials, bei dem die Kontraktionsphase in die Relaxationsphase übergeht, ist veränderlich. Allen Anzeichen nach hängt sie von der intracellulären Ca-Konzentration ab.B.Es fand sich eine lineare Korrelation zwischen der Dauer eines einzelnen verlängerten AP bzw. der Dauer sämtlicher Aktionspotentiale in einer interpolierten Salve von Extrasystolen und dem Gesamtzuwachs der mechanischen Spannung. Diese Beziehung spiegelt wahrscheinlich die Beladung des Koppelungssystemes mit Kontraktions-wirksamen Ca++ wider.C.Weiterhin wurde eine konstante Beziehung gefunden zwischen der treppenförmigen Kontraktionszunahme nach einem Frequenzanstieg, nach Erhöhung der Ca-Konzentration im Medium, nach Abkühlung oder nach der Verlängerung des AP auf der einen Seite und der parallelen schrittweisen Verkürzung der Repolarisation auf der anderen Seite. Es wird vermutet, daß dieser Beziehung der gleichzeitige Einfluß der Ca-Ionen auf den contractilen Apparat und auf die transmembranären Ionenbewegungen (möglicherweise die Erhöhung des K+-Effluxes) zugrunde liegt. Diese charakteristischen Beziehungen könnten die Grundlage für eine negative Rückkoppelung sein. (Die beschriebenen Korrelationen sind konstant reproduzierbar und statistisch bedeutungsvoll.)

Variability of Phase Shift Between Blood Pressure and Heart Rate Fluctuations A Marker of Short-Term Circulation Control

Background We postulated that the variability of the phase shift between blood pressure and heart rate fluctuation near the frequency of 0.10 Hz might be useful in assessing autonomic circulatory control. Methods and Results We tested this hypothesis in 4 groups of subjects: 28 young, healthy individuals; 13 elderly healthy individuals; 25 patients with coronary heart disease; and 19 patients with a planned or implanted cardioverterdefibrillator (ICD recipients). Data from 5 minutes of free breathing and at 2 different, controlled breathing frequencies (0.10 and 0.33 Hz) were used. Clear differences (P<0.001) in variability of phase were evident between the ICD recipients and all other groups. Furthermore, at a breathing frequency of 0.10 Hz, differences in baroreflex sensitivity (P<0.01) also became evident, even though these differences were not apparent at the 0.33‐Hz breathing frequency. Conclusions—The frequency of 0.10 Hz represents a useful and potentially important one for controlled breathing, at which differences in blood pressure‐RR interactions become evident. These interactions, whether computed as a variability of phase to define stability of the blood pressure‐heart rate interaction or defined as the baroreflex sensitivity to define the gain in heart rate response to blood pressure changes, are significantly different in patients at risk for sudden arrhythmic death. In young versus older healthy individuals, only baroreflex gain is different, with the variability of phase being similar in both groups. These measurements of short‐term circulatory control might help in risk stratification for sudden cardiac death. (Circulation. 2003;108:292‐297.)

Slow inward current and action potentials of papillary muscles under non-steady state conditions.

Summary1.The relationship of the contractile response of cat papillary muscles and of the slow inward current, recorded under voltage clamp conditions (single sucrose gap), has been studied. The preparations were driven at a rate of 30 per min at 31° C. Both variables were recorded during a train of 7 identical clamp depolarizations (for 1 s from resting potential to −15 to +40 mV). The contractility increased severalfold and reached the steady state within 5–6 consecutive depolarizations.2.The voltage-dependence of slow inward current was confirmed: maximum was found at depolarizations near 0 mV. On repetition of clamp pulses the slow current gradually diminished in amplitude and was more slowly activated and inactivated. The shift of the current-voltage curve indicated a decrease of the reversal potential.3.Under non-steady state conditions the amplitude of the slow current was found to correlate closely with the magnitude of the contractile response at any given level of depolarization. The relation was linear with negative slope. The largest contractile response was not found at voltages which elicited maximum slow current.4.The progressive decrease of the slow current during repetition of voltage clamp depolarizations is not significantly affected by inadequate time for recovery of slowly changing conductances, since it occurs also at stimulation frequency 15 per min and the slow current remains virtually unaltered after 20 s period of quiescence.5.The course of total ionic current during phase 1 and 2 of action potential was reconstructed from a family of current curves obtained as a response to clamp depolarizations to various voltages, respecting the contractility-dependence of the current. The resulting course was correlated with the first derivative of action potential. A general conformity was ascertained.6.The correlation of slow inward current with action potential configuration indicates that the rate of its activation determines the depth of the notch separating spike and plateau, its magnitude determines the voltage of the plateau phase and its rate of inactivation affects repolarization.7.It is concluded that the described simultaneous changes of mechanical and electrical phenomena might be due to increased [Ca]i, which is responsible for more intense activation of the contractile proteins on the one hand, and decreased driving force of the slow inward current, carried by Ca ions, on the other.

Activity-dependent changes of slow inward current in ventricular heart muscle

Abstract1.The relationships between membrane voltage, contractile force and slow inward current were studied in cat and dog papillary muscles or trabeculae employing the double sucrose gap voltage clamp technique. The experiments were performed at 30°C and the preparations were stimulated at a frequency of 0.5 Hz.2.The known relationships between steady state contractile force, slow inward current and membrane voltage were confirmed.3.Under non-steady state conditions the slow inward current decreases during ascending and increases during descending contraction staircases when the clamp steps of the test train exceed about 60 mV from resting level. Depolarization clamp steps below 60 mV produce parallel changes of the slow inward current and contractile force. Those clamp conditions which increase the contractile force shift the threshold of Isi and of contraction towards more negative values.4.During ascending staircases an increasing background outward current was regularly observed together with diminshing slow inward current.5.The reported current transients agree with the changes of action potential configuration during mechanical transients: the prolongation of plateau during descending staircases corresponds to an increase, and the shortening of action potential during late repolarization corresponds to a decrease of slow inward current in the respective voltage ranges.6.The slow inward current was tentatively separated into two components. The main component is inversely proportional to contractile force and it exhibits the well known current-voltage relationship for this current. The other one is directly proportional to contractile force and may be related to a regenerative response of reticular membranes.

Effect of epinephrine on the duration of action potential of papillary muscles

Im Gegensatz zur Kontrollbedingung (Tyrodelösung 1.8 mM Ca, 31°C, Reizfrequenz 30/min) ruft Adrenalin 6×10−6 M im Ca-freien Milieu eine significante Verlängerung der Aktionspotenziale hervor. Die Zugabe von Ca2+ kehrt die Aktionspotenzialdauer mit voller Entwicklung der positiv inotropen Wirkung zu Ausgangswerten zurück.

A contraction-related component of slow inward current in dog ventricular muscle and its relation to Na(+)-Ca2+ exchange.

1. The slow inward current component related to contraction (Isic) was studied in voltage clamp experiments on canine ventricular trabeculae at 30 degrees C with the aims of (a) estimating its relation to electrogenic Na(+)‐Ca2+ exchange and (b) comparing it with similar currents as reported in cardiac myocytes. 2. Isic may be recorded under conditions of augmented contractility in response to depolarizing pulses below the threshold of the classic slow inward current (presumably mediated by L‐type Ca2+ channels). In responses to identical depolarizing clamp pulses the peak value of Isic is directly related to the amplitude of contraction (Fmax). Isic peaks about 60 ms after the onset of depolarization and declines with a half‐time of about 110 ms. 3. The voltage threshold of Isic activation is the same as the threshold of contraction. The positive inotropic clamp preconditions shift both thresholds to more negative values of membrane voltage, i.e. below the threshold of the classic slow inward current. 4. Isic may also be recorded as a slowly decaying inwardly directed current ‘tail’ after depolarizing pulses. In this representation the peak value of Isic changes with duration of the depolarizing pulses, again in parallel with Fmax. In response to pulses shorter than 100 ms both variables increase with depolarization time. If initial conditions remain constant, further prolongation of the pulse does not significantly influence either one (tail currents follow a common envelope). 5. Isic differs from classic slow inward current by: (a) its direct relation to contraction, (b) the slower decay of the current tail on repolarization, (c) slower restitution corresponding to the mechanical restitution, (d) its relative insensitivity to Ca(2+)‐blocking agents (the decrease of Isic is secondary to the negative inotropic of Ca(2+)‐blocking agents (the decrease of Isic is secondary to the negative inotropic effect) and (e) its disappearance after Sr2+ substitution for Ca2+. 6. The manifestations of Isic in multicellular preparations do not differ significantly from those reported in isolated myocytes (in contrast to calcium current). 7. The analysis of the correlation between Isic and Fmax transients during trains of identical test depolarizing pulses at variable extra‐ and intracellular ionic concentrations (changes of [Ca2+]o, 50% Li+ substitution for Na+, strophanthidin) indicate that the observed effects conform to the predictions based on a quantitative model of Na(+)‐Ca2+ exchange. 8. It is concluded that Isic is activated by a transient increase of [Ca2+]i, in consequence of the release from the reticular stores.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of autonomic nervous system dysfunction by phase shift and XYt graph methods

BACKGROUND: We postulated that the phase shift between blood pressure and heart rate fluctuation near the frequency of 0.10 Hz might be useful in assessing autonomic circulatory control. CONCLUSIONS: The frequency of 0.10 Hz represents a useful and potentially important one for controlled breathing, at which differences in blood pressure-RR interactions become evident. These interactions, whether computed as a variability of phase to define stability of the blood pressure-heart rate interaction or defined as the baroreflex sensitivity to define the gain in heart rate response to blood pressure changes, are significantly different in patients at risk for sudden arrhythmic death.

Time-frequency interpretation of ultra-high-frequency QRS components

This paper presents a method for time-frequency representation of ultra-high-frequency components in the QRS complex in high-sensitivity and high-frequency electrocardiography signal measurement. Time-frequency interpretation forms shapes that look like fire - FLAMES. The width, intensity and position of FLAMES characterise the electrical properties of the human heart. FLAMES are able to differentiate electrical changes during asynchronous heart muscle activation and identify changes in electrical activation during heart ischemia, infarctions and structural changes of the myocardium. The difference in FLAMES is demonstrated in healthy young subject and heart-failure subject.

Depth of Breathing and Baroreflex Sensitivity

The aim of the study: Comparison between breathing on the 0.1 Hz and 0.33 Hz. At a breathing frequency of 0.10 Hz, differences in baroreflex sensitivity (P<0.01) became evident, even though these differences were not apparent at the 0.33-Hz breathing frequency. CONCLUSIONS: The frequency of 0.10 Hz represents a useful and potentially important one for controlled breathing, at which differences in blood pressure-RR interactions become evident. These measurements of short-term circulatory control might help in risk stratification for sudden cardiac death.