Gordon K. Moe

Nonuniform Recovery of Excitability in Ventricular Muscle

Recovery of excitability of ventricular muscle was measured at numerous points in exposed dog ventricles at varying distances along six radial axes from a primary point of stimulation. Temporal dispersion of recovery of excitability at various points equidistant from the point of stimulation was minimal after a basic beat but was increased after an early premature beat. The degree of dispersion following a basic beat was increased by stimulation of the cardiac sympathetic nerves, administration of chloroform, ouabain intoxication, administration of higher doses of quinidine, myocardial ischemia, and hypothermia, but it was decreased by administration of sympathomimetic amines.

Adrenergic Effects on Ventricular Vulnerability

Effects of stimulation of the cardiac sympathetic nerves and intravenous administration of sympathomimetic amines on the multiple response or fibrillation threshold (VMRT) and on other properties of the dog ventricles were compared. Stimulation of the cardiac sympathetic nerves decreased the VMRT. Administration of sympathomimetic amines caused a brief decrease in the VMRT followed by a sustained increase. Temporal dispersion of recovery of excitability and the degree of ventricular vulnerability were closely related; the ventricle was more vulnerable to fibrillation when the dispersion was increased. The hyperkalemic effect of epinephrine was not responsible for the observed changes in ventricular vulnerability.

Temporal dispersion of recovery of excitability in atrium and ventricle as a function of heart rate

Abstract Temporal dispersion of recovery of excitability, measured as the range of local refractory period durations at numerous sites on the atrial and ventricular surfaces, was found to be a direct function of the basic cycle length except at very rapid driving frequencies. In the atrium, spontaneous ectopic activity followed early premature stimuli at slow but not at fast driving frequencies. In the ventricle, the fibrillation threshold was significantly lower at slow than at high basic frequencies. It was concluded that spontaneous closely coupled beats occurring at slow ventricular rates in A-V dissociation may result from asynchrony in the repolarization of adjacent excitable units.

Demonstration of a Dual A-V Nodal Conduction System in the Isolated Rabbit Heart

The intranodal propagation of atrial and ventricular echoes in in-vitro preparations of the rabbit heart was traced from microelectrode records at many puncture sites. Composite records indicate that the upper part of the node can be functionally and spatially dissociated into two pathways (α and β), which communicate with a final common pathway (FCP) about halfway between the atrium and the His bundle. Atrial echoes, induced by premature atrial stimulation, traverse the α pathway and return to the atrium from the middle part of the node over the β route; echoes can occur without propagation of the premature response to the ventricle. Ventricular echoes, induced by premature stimulation of the His bundle, pass from the FCP to the atrium over the α route, and back to the FCP over the β route. Repetitive reciprocation, in the nature of an intranodal circus movement, was commonly observed. The results completely substantiate previous conclusions based on indirect observations in the dog heart.

Effect of electrotonic potentials on pacemaker activity of canine Purkinje fibers in relation to parasystole.

Isolated false tendons excised from dog hearts were mounted hi a three-chamber tissue bath. Isotonic sucrose solution was perfused hi the central chamber to provide a region of depressed conductivity between the fiber segments in chambers 1 and 3, which were perfused with Tyrodes solution. The electrotonic influence of spontaneous or driven responses evoked in chamber 3 during the first half of the spontaneous cycle of a chamber 1 pacemaker delayed the next spontaneous discharge. This effect changed to acceleration when the chamber 3 segment fired during the second half of the spontaneous cycle. We found that subthreshold depolarizing current pulses 50–300 msec applied across the sucrose gap caused similar degrees of delay or acceleration. Furthermore, hyperpolariziiig currents caused the reverse pattern. The results indicate that the discharge pattern of a parasystolic focus may be altered by the electrotonic influence of activity in the surrounding tissue. The significance of these findings is considered in relation to the mechanism of production of parasystolic rhythms.

Aberrant A-V Impulse Propagation in the Dog Heart: A Study of Functional Bundle Branch Block

Excessive delay and configurational change of ventricular responses to atrial premature beats, previously attributed to dissociation within the A-V node, were shown to be due to functional block of the right bundle branch. It was found that the refractory period (RP) of the right bundle branch often exceeded the functional refractory period (FRP) of the A-V node at slow heart rates, permitting an early premature atrial response to reach the ventricles before recovery of the right bundle. Vagal stimulation and rapid driving frequencies, by delaying the intranodal transit of the premature response, prevented the exposure of bundle branch block. Epinephrine in low doses sometimes facilitated its occurrence. Premature responses initiated in the His bundle in open heart preparations were commonly blocked in the right bundle under conditions in which atrial premature responses were normally propagated to the ventricles. Evidence was obtained in such preparations that the portion of the right bundle system beyond the site of the block was activated retrogradely from the left side. Under certain conditions the retrograde activation process returned to the His bundle and the atrium as an echo.

Effect of Intervals between Doses on the Development of Tolerance to Isosorbide Dinitrate

We studied the development of tolerance to isosorbide dinitrate in 12 patients with chronic stable angina pectoris. The effect of 30 mg of isosorbide dinitrate on treadmill exercise performance was assessed before and at one, three, and five hours after a single dose. As compared with placebo, the drug increased treadmill walking time until the onset of angina and until the development of moderate angina over the five-hour observation period (P less than 0.05). The patients then received 30 mg of isosorbide dinitrate twice, three times, and four times daily for a period of one week, and exercise performance was assessed before and at one, three, and five hours after the final morning dose. During sustained treatment two and three times daily, treadmill walking time was longer throughout the five-hour testing period than during the placebo phase (P less than 0.05). In contrast, during treatment four times daily, treadmill walking time was prolonged at one hour (P less than 0.05) but not at three and five hours after the last dose. We conclude that tolerance to the clinical effects of isosorbide dinitrate develops with a sustained dosage of 30 mg four times daily, but not when the drug is given two or three times daily.

Interaction of Transmembrane Potentials in Canine Purkinje Fibers and at Purkinje Fiber-Muscle Junctions

Interactions between Purkinje fibers and ventricular muscle were studied in canine Purkinje-papillary muscle preparations. The change in duration of action potentials across the junctions between Purkinje fibers and papillary muscle was continuously graded, not abrupt. The transmembrane action potentials were longest in the false tendons and progressively shorter in more peripheral fibers. The responses of terminal Purkinje fibers and of neighboring muscle cells differed little in duration. The shortest action potentials were found in muscle fibers located in regions devoid of specialized tissue (tip of papillary muscle). These results suggest that the intercellular connections, including those at the junctions, offer relatively low resistance to current flow. During repolarization the current flowing between neighboring elements with intrinsically different repolarization times should therefore minimize the disparity in action potential durations on the two sides of the junctional site; a continuously graded change in duration would result. Because of this continuous gradation, premature ventricular responses initiated at the tip of the papillary muscle could be blocked, depending on the degree of prematurity, at various levels in muscle fibers functionally close to terminal Purkinje fibers or within the Purkinje system.

Effect of calcium on acetylstrophanthidin-induced transient depolarizations in canine Purkinje tissue.

The role of calcium ions (Ca2+) in the generation of transient depolarizations (TDs) by acetylstrophanthidin was examined. Transmembrane activity was recorded from isolated canine false tendons exposed to acetylstrophanthidin; concentrations from 7.5 × 10−8 to 2 × 10−7 g/ml caused TDs coupled to driven action potentials and depressed slow diastolic depolarization. TDs could reach threshold and induce extrasystoles. Elevation of the Ca2+ concentration increased the amplitude of TDs induced by acetylstrophanthidin. High Ca2+ concentration (12.5 mM) caused TDs and depression of slow diastolic depolarization in the absence of acetylstrophanthidin. Elevation of potassium (K+) concentration depressed and reduction of K+ concentration potentiated TDs caused by either acetylstrophanthidin or high Ca2+ concentration. The production of TDs and the depression of slow diastolic depolarization by acetylstrophanthidin were reversed by reduction of the Ca2+ concentration or addition of manganese (2 mM) to the superfusing Tyrodes solution. The results suggest that TDs and arrhythmias produced by acetylstrophanthidin may be caused by a transient Ca2+ influx.

Fibrillation Threshold of Premature Ventricular Responses

The degree of temporal dispersion of recovery of excitability of premature ventricular responses, estimated as the range of local refractory periods at various points on the surface of the right ventricle, is greater within a radius of 10 to 15 mm from the stimulated site than at greater distances. The fibrillation threshold of early premature beats is significantly lower than that of responses initiated in fully excitable tissue. The effect of prematurity on the fibrillation threshold is greater at points near the site of origin of the premature response. The observed spatial and temporal relationships suggest that the fibrillation threshold is related inversely to the degree of asymmetry in the excitable field.