Effect of Transmural Differences in Excitation-Contraction Delay and Contraction Velocity on Left Ventricle Isovolumic Contraction: A Simulation Study.

Recent studies have shown that left ventricle (LV) exhibits considerable transmural differences in active mechanical properties induced by transmural differences in electrical activity, excitation-contraction coupling, and contractile properties of individual myocytes. It was shown that the time between electrical and mechanical activation of myocytes (electromechanical delay: EMD) decreases from subendocardium to subepicardium and, on the contrary, the myocyte shortening velocity (MSV) increases in the same direction. To investigate the physiological importance of this inhomogeneity, we developed a new finite element model of LV incorporating the observed transmural gradients in EMD and MSV. Comparative simulations with the model showed that when EMD or MSV or both were set constant across the LV wall, the LV contractility during isovolumic contraction (IVC) decreased significantly ((dp/dt)max⁡  was reduced by 2 to 38% and IVC was prolonged by 18 to 73%). This was accompanied by an increase of transmural differences in wall stress. These results suggest that the transmural differences in EMD and MSV play an important role in physiological contractility of LV by synchronising the contraction of individual layers of ventricular wall during the systole. Reduction or enhancement of these differences may therefore impair the function of LV and contribute to heart failure.

Heart rate and increased intravascular volume.

The objective was to establish whether an intravascular volume increase leads to a heart rate (HR) increase without increased sympathetic tonus. HR changes at rest and at deep breathing (6/min - simulated increase of atrial filling pressure) were measured in patients after heart transplantation. Evaluation of dependency of HR changes on breathing depth was done through a new time series methodology. The data was evaluated through graphs displaying a significant increase in the graph area at deep breathing, when compared with breathing at rest (p<0.01). We presume that an increase in HR corresponds to increased intravascular volume and malfunctioning kidneys.

Pericardial abscess--a rare complication of sepsis.

Pericardial abscess is a very rare complication of sepsis. Authors describe the case of a 69-year-old woman. In her case staphylococcus sepsis led to pericardial abscess. During the course positive blood cultures (3x) indicated the sepsis and pus was obtained from the left pleural cavity (pleuropneumonia). Concomitant purulent process in the left shoulder also was noted. Decline immunity due to long-standing corticoid therapy (prednisone) for proctocolitis idiopathica was observed. Following antibiotic treatment successful surgical evacuation of the pericardial abscess was performed.

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)

Cardiac arrhythmias in chronic heart failure.

It has been proven that treatment of chronic heart failure (CHF) with some modern drugs is able to reduce mortality in groups of patients with the severest grades of this disease. The risk of sudden death has been unchanged, however. Out of 49 patients on long-term follow-up, 28 patients are surviving (group A) and 21 died (group B). 52.3% of the dead patients died suddenly. Eight patients in NYHA classes I-II died, all of them suddenly. Contrary to this, sudden death was the cause of death only in three of 13 patients in NYHA classes III-IV (p < 0.001). More severe heart failure was present in group B (NYHA class 2.95 +/- 0.96 vs. 2.18 +/- 0.48 in group A--p < 0.1). Antiarrhythmic drugs were given more frequently in group B (in 47.6% of pts vs. 17.9% in group A--p < 0.05). It is concluded that the occurrence of sudden death is higher in patients with less severe forms of CHF and has not been reduced by the means employed. Use of antiarrhythmic drugs may be dangerous and their indication should be based on results of a comprehensive examination. Use of the implantable cardioverter-defibrillator seems to be the most promising approach in indicated cases.

Significance of the site of premature excitation for the left and right ventricular performance in open chest dogs.

The haemodynamic response to premature excitation was studied in open-chest dog hearts. Intraventricular pressure, dP/dt and outflow rate of the left and right heart (5 experiments each) were compared at variable preextrasystolic intervals and with the stimulation at three different sites (left ventricle--LV apex and base, right ventricle--RV free wall). In both ventricles and at any driving interval the reduction of all extrasystolic parameters is significantly more pronounced on ipsilateral stimulation. This reduction is apparent even at the fusion interval, demonstrating the importance of normal spread of excitation. The differences between apex and base stimulation are, however, only insignificant. The outflow valves opening interval greatly differs in aorta and pulmonary artery, namely if LV is stimulated, which results in a considerable disproportion between LV and RV extrasystolic stroke volumes. The extrasystolic augmentation is revealed by all parameters in the right heart but is surprisingly absent in the peak pressure and relaxation rate (dP/dt) in the LV.

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

1. 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 degrees 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 diminishing 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 local anaesthetics (mesocain) on membrane properties of cat papillary muscle.

In 28 experiments on cat papillary muscles the effect of mesocain (generically related to lidocaine) was studied on transmembrane currents (rapid inward INa, slow inward Isi, outward Io), on the configuration and (dV/dt)max of the action potential, on the refractory period and on isometric tension. The experiments were performed using either voltage clamp method (double sucrose gap) or microelectrode technique. All three transmembrane currents are inhibited by mesocain in a dose-dependent manner. The effect becomes measurable at 10(-6) mol/1 on INa, at 10(-5) mol/1 on Isi and at 5 X 10(-5) mol/1 on Il. INa is blocked at 10(-3) mol/1 concentration. These changes correlate with the measured alterations of action potentials: i.e. a decreased (dV/dt) max and overshoot, lower voltage and shortening of the plateau phase, slower rate of late repolarizaion. The negative inotropic effect appeared with the same treshold concentration as Isi; at higher concentrations, however, this effect was relatively much greater. The recovery of excitability measured by the interval-dependence of (dV/dt) max was prolonged 5 times on the average by mesocain at 10(-4) mol/1 and the effective refractory period was delayed beyond complete repolarization. It is concluded that the main effect of mesocain also involves a delayed kinetics of recovery from inactivation of the Na carrying system.

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

1. 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 degrees 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.