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Myocardial cells from chick embryos were cultured using a method which results in cell morphology and action potentials showing greater similarity to that of adult cells than to cells grown with standard methods of culture. The cells were paced by means of rectangular field stimuli (2 msec 2-5 times diastolic threshold). When the stimulus was given during the descending branch of the previous action potential, the action potential developed dissociation between a fast-rise component with short duration and a slow-rise component with longer duration. This dissociation was best in cells with an intermediate rate of rise of the spontaneous action potential and may be caused by different rates of reactivation of the slow and fast membrane excitation channels.

Myocardial cells isolated from 8-day chick embryos were grown in monolayer culture under conditions that produce “standard embryonic” and “adult-type” cells. These cells were subjected to electric field stimulation that had a waveshape and intensities similar to those used in clinical electric countershock procedures. Photocell mechanograms obtained before, during, and after stimulation were correlated with simultaneously measured transmembrane potentials to determine the relationship between membrane polarization and arrhythmia production that occured after the stimulus. The results of these experiments demonstrate that a predictable sequence of mechanical responses occurs after stimuli ranging in intensity from 6 to 200 V/cm. This sequence, which closely resembles that observed in vivo after similar stimulation intensities, consists of a single response (activation), tachyarrhythmia, relaxed arrest followed by transient tachyarrhythmia, arrest with contracture, and cellular fibrillation. This diverse pattern of arrhythmias is associated with a prolonged depolarization of the cell membrane which increases with the intensity of the applied stimulus. It is probable that this depolarization is caused by a transient electromechanical deformation of the cell membrane during the shock. These findings contribute to a better understanding of the causes of the arrhythmias that appear after clinical and experimental electric countershock procedures.

Isolated rabbit hearts were perfused with Krebs-Henseleit solution deficient in K, Ca or both. Ventricular monophasic action potentials registered with the suction electrode, electrocardiograms and intraventricular pressures were recorded simultaneously for periods up to 20 minutes. Perfusion with K-deficient solutions resulted in a brief initial prolongation of the entire descending limb of the action potential and of the T wave, followed by progressive increase in slope of the initial portion and decrease in slope of the terminal portion of the action potential. During this time the T wave became shorter and a U-wave-like deflection occupying the entire diastole developed. QRS showed progressive prolongation. Finally, A-V conduction disturbances, ectopic beats and ventricular fibrillation developed. The force of contraction increased slightly. Perfusion with Ca-deficient solutions decreased the slope of the initial portion while increasing the slope of the terminal portion of the action potential. This was accompanied by prolongation of the ST- segment and reversal in the direction of the T wave. The duration of the action potential reached a maximum after 40–80 seconds of perfusion, while the force of contraction decreased progessively. Perfusion with solutions without potassium and calcium prolonged the initial as well as terminal portion of the action potential.

In view of the growing recognition of the pathogenic role of the adrenosympathetic humoral neurotransmitters in the heart muscle as chemical anoxia-producing agents, cardiac "sympathin" was extracted and assayed both colorimetrically and biologically, and some of its chemical and pharmacodynamic properties were studied in detail. It proved to be at least in part identical with nor-epinephrine (arterenol) and to exert effects analogous to those of epinephrine and nor-epinephrine upon blood pressure, heart rate and the electrocardiogram (depression or inversion of the T wave). Its action was intensified by cocaine and counteracted by nitroglycerine.

The pattern of arrhythmias following capacitor discharges of increasing amplitude, which have been observed by the authors in cultured myocardial cells from chick embryos, was compared to the arrhythmia patterns caused by similar discharges in experimental animals and humans, as reported in the literature. While the absolute voltages and currents causing each type of arrhythmia showed great variation, the scatter decreased considerably when the stimulus level was recalculated on the basis of peak current density in myocardial tissue, and was reduced further when the peak potential gradient at the cell level was used as the common basis of comparison. The similarity in the arrhythmia patterns and in the voltage gradients at which they occur indicates that the mechanism of these arrhythmias may be similar in cultured cells and intact animals and humans.

The direct-current magnetocardiogram not only shows the features usually seen on the electrocardiogram, but also shows the T-Q (baseline) shift due to cardiac injury current. The first direct-current magnetocardiogram measurements of the human heart are presented here. The hypothesis tested is that there is no injury current associated with the S-T shift seen in two electrocardiogram abnormalities: early repolarization, and left bundle branch block. The data from three typical early repolarization subjects and one typical left bundle branch block patient are presented. It is found, in each case, that although there is appreciable S-T shift, there is essentially no baseline shift on the direct-current magnetocardiogram. The absence of baseline shift proves that the S-T shifts in these cases are not "apparent" shifts, caused by a dc injury current which is interrupted during the S-T interval; instead, these are "true" S-T shifts caused by a current flowing only during systole, presumably due to an altered repolarization of the ventricles. It is also found that the direct-current magnetocardiogram does not have routine clinical application because of a practical problem. This is the presence of false baseline shifts due to noncardiac currents, mostly in the gastrointestinal tract, which could be suppressed in only about one-third of the subjects. However, the direct-current magnetocardiogram may be useful as a research tool, for clarifying the cause of the S-T shift in selected subjects.

Myocardial cells from chick embryos were cultured using a method which results in cell morphology and action potentials showing greater similarity to that of adult cells than to cells grown with standard methods of culture. The cells were paced by means of rectangular field stimuli (2 msec 2-5 times diastolic threshold). When the stimulus was given during the descending branch of the previous action potential, the action potential developed dissociation between a fast-rise component with short duration and a slow-rise component with longer duration. This dissociation was best in cells with an intermediate rate of rise of the spontaneous action potential and may be caused by different rates of reactivation of the slow and fast membrane excitation channels.

The direct-current magnetocardiogram, which shows the T-Q (baseline) shift, is used to clarify the cause of S-T depression induced by stress testing in the human heart. Measurements are made of the amount of baseline shift associated with the S-T depression. Results are presented of a well-documented patient, with typical coronary artery disease, undergoing a two-step exercise test. Before exercise, there was no S-T or baseline shift. During exercise, the S-T segment became depressed and the baseline segment was simultaneously elevated, at about 70% of the S-T amplitude. After termination of exercise, the baseline elevation disappeared somewhat more rapidly than the S-T depression. These results were consistent in repeated tests of this patient. Because the baseline shift is a reflection of an injury current, these results confirm the belief that exercise-induced S-T depression is mostly due to an injury current which is interrupted during the S-T interval. The baseline shift seen here is the first non-invasive measurement of an injury current in the human heart, and its presence and time-course generally agree with measurements in the animal heart. This work also confirms that the direct-current magnetocardiogram, although not practical for clinical purposes, is useful as a research tool.

We studied the structural alterations that follow the application of currents similar to those used in clinical electric countershock procedures in cultured chick myocardial cells. Myocardial cells 48 hours in culture were subjected to electric field stimulation. The cells then were fixed for electron-microscope examination 30 seconds postshock. The ultrastructural alterations that appeared after an 80 V/cm shock included the appearance of >25% of the mitochondria per cell in the "condensed" configuration and mitochondria with swirled or tubular cristae. Large-amplitude swelling of the mitochondria and swollen endoplasmic reticulum also were observed in a few cells. The alterations that appeared after a 200 V/cm shock included contracture and disorganization of the myofibrils, large-amplitude swelling and loss of cristae in the mitochondria, swollen endoplasmic reticulum and nuclear envelope, and intracellular edema. The degree of ultrastructural change was dependent on the intensity of the shock. These structural alterations are consistent with an osmotic imbalance which occurs during a shock-induced prolonged depolarization of the cell membrane (Jones et al., 1978a), possibly due to a transient dielectric breakdown during the shock, and may underlie the arrhythmias and necrosis which often occur after high-intensity clinical and experimental eountershock procedures in vivo. Circ Res 46: 387-394, 1980

1.1. In five cases of recurrent hiccup the hiccup sounds were recorded synchronously with three leads of the electrocardiogram. 2.2. In three cases the hiccup movements caused electrocardiographic artifacts which could be confused with U waves or with auricular and ventricular premature beats. 3.3. The hiccup sounds as well as the artifacts always occurred 0.17 to 0.40 seconds after the beginning of the QRS complex of the electrocardiogram, and in some cases two successive heart beats were followed by hiccup movements. It is postulated that in the reported cases the hiccup was caused by stimulation of one of the phrenic nerves by the electric currents registering as the QRS complex of the electrocardiogram. 4.4. The hyperirritability of the phrenic nerves in the reported cases was probably due to a decrease in the ionized serum calcium or to alkalosis.

The action potentials recorded from heart muscle with a suction electrode have been compared to those recorded with an intracellular microelectrode. It has been found that if the suction electrode is properly used the monophasic potentials recorded with it may be taken as a reliable index of the time of arrival of excitation at the electrode and as a reliable index of the shape of the action potential during the entire phase of repolarization. The suction electrode potentials differ from the microelectrode potentials in showing a lower rise velocity, a smaller amplitude, a quantitatively different reversal or overshoot and, in the beating heart, ‘afterpotentials’ caused by mechanical effects. When the shape of the action potential, as observed with the microelectrode, is changed by ions such as K+ or Ca++ a similar change is observed in the potential recorded with the suction electrodes.

THE electrocardiographic exercise test is a well established procedure in the diagnosis of coronary insufficiency. The method most widely used in America is the two-step test of Master.1 2 3 4 5 6 Master has standardized the exercise for the individual subject on the basis of sex, age and weight. One of the objections raised against the procedure was that the exercise was of short duration and did not permit the achievement of a steady state. However, the results of a recently published comparative study between the double Master two-step test and the exercise on a treadmill, which was sufficiently long to achieve the steady . . .

Summary An analysis is made of the ventricular complex in personal and published cases of pre-excitation (typical or atypical Wolff-Parkinson-White Syndrome) in which intraventricular or atrio-ventricular conduction disturbances were present before appearance of pre-excitation. On the basis of this analysis the conclusion is made that a prolonged or normal P-R interval or a shortening of the QRS interval after appearance of pre-excitation is in favor of a location of the aberrantly conducting A-V pathways in or near the A-V node. In one of the illustrated cases the pre-excitation pattern was accompanied by earlier beginning of ventricular contraction without change in the time of appearance of the carotid pulse.

In connection with the problem of the possible role played by the sympathomimetic neurohormones (nor-epinephrine and epinephrine) in the pathogenesis of essential hypertension, interest has been focused lately on substances which are capable of abnormally intensifying the vasoconstrictor power of epinephrine in the mesentery of the rat and the perfused rabbit's ear, such as the chemically undefined agent "VEM" which originates in the kidney (1) and protein fractions, extracted from the kidneys and other tissues, as well as hypertensin and tyrosin (2). A participation of adrenal cortical steroids in such "sensitizing" mechanisms is suggested by the restoration of the impaired VEM formation in the