Transmembrane activity was recorded from canine false tendons bathed with Tyrode's solution at 37°C. Stimulus patterns provided a 3-second pause after every ten beats. Acetylstrophanthidin was infused at concentrations up to 2x10 -7 g/ml. One or two transient depolarizations (TDs) followed the last driven response of each series. The appearance of TDs was associated with depression of normal phase-4 depolarization. The peak of the earliest TD (TD-1) occurred at an interval approximately equal to the basic cycle length. The later TD (TD-2) occurred at about twice the basic cycle length. Coupling intervals were determined primarily by the last cycle length. The amplitude of TD-1 was maximal when the basic cycle length was 600 msec, but TD-2 continued to increase as the basic cycle length diminished further. The amplitude of both TDs increased with the number of beats in the train. Either or both could reach threshold and induce single extrasystoles or trains of extrasystoles. TDs could be induced to reach threshold after each driven response, resulting in sustained bigeminal rhythms with fixed coupling. Possibly TDs provide a mechanism for various clinically observed arrhythmias induced by cardiac glycosides.

No abstract

In canine Purkinje fiber-papillary muscle preparations it was shown directly that electrotonic spread can take place across the junctions between Purkinje fibers and ordinary muscle fibers (P-M junctions). The P-M delay recorded during orthodromic propagation varied considerably within any given preparation. Moderate increases in the external concentration of K + (up to 6 ITIM) consistently decreased the P-M delay; when the concentration of external K + was increased to 8 HIM the P-M delay increased. With larger concentrations of K + (10 to 11 mM), total conduction block from the terminal Purkinje fibers to the muscle occurred; under the same conditions antidromic propagation from muscle to Purkinje fiber was still possible. The results can be explained satisfactorily by assuming that propagation across the P-M junction is electrical and that the geometry of the functional syncytium changes progressively from a cable-like system at the level of the terminal Purkinje fibers to a two-or threedimensional irregular syncytium at the bulk of the myocardial mass.

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.

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.

The electrical threshold of A-V nodal cells of isolated rabbit heart preparations was estimated by techniques which permitted stimulation and recording through the same micropipette. Cells within the node were significantly less excitable than adjacent atrial and ventricular tissues; thresholds exceeded 5 X 10~~° amp in some instances. Recovery of excitability was delayed well beyond repolarization; in cells of the midnodal region, "diastolic" threshold was not attained until 0.2 to 0.5 seconds after restoration of resting membrane potential. A cumulative effect of frequency upon excitability (fatigue) was demonstrated. At high driving rates, the lag in recovery was further delayed, and the late diastolic threshold was increased. Responses to single-cell stimulation indicate that summation may be an important feature of propagation within the node. ADDITIONAL KEY WORDS fatigue of A-V transmission atrioventricular conduction summation in A-V nodeSchematic diagram of circuits used for intraceUular stimulation and recording. ME = microelectrode; P = potentiometer; C = calibrator; A 2 = amplifier for recording transmembrane action potential; Aj = current monitor.

In isolated canine papillary muscle-false tendon preparations it was possible by selecting the pattern of stimulation to obtain conduction block within the peripheral distribution of the Purkinje network. Action potentials recorded just proximal to the site of block were always extremely brief in duration; refractory periods were abbreviated accordingly. When propagation from specialized fibers to muscle fibers was made very critical, conduction block occurred at some Purkinje-muscle junctions while propagation continued through others. Under these conditions very early reentrant activity could be obtained in terminal Purkinje fibers. With proper timing, the impulse propagated back to the false tendon and emerged as a closely coupled extrasystole. Occasionally, the activity returned again to muscle and resulted in a double reentry. Electrotonic shortening of action potentials of Purkinje fibers at relatively long distances upstream from a site of block facilitated the reentry of proximal elements. Partial reentry of the Purkinje system created conditions favoring fractionation of the reentrant wave front-KEY WORDS unidirectional conduction block refractory period of Purkinje fibers Purkinje-muscle junctions repetitive activity in ventricular tissue abbreviation of action potentials electronus in heart muscle cardiac arrhythmias• The concept of reentry as a mechanism for initiating ectopic activity dates back to the early experiments of Schmitt and Erlanger (1). There is now general agreement among investigators that the necessary conditions for reentry include: (1) unidirectional block of an impulse in one or more regions of the heart; (2) slow passage of the impulse over an alternative route; (3) delayed excitation of the tissue just distal to the blocked site; and (4) reexcitation of the tissue proximal to the site of block. This last event can take place only if the conduction time over the alterna- This work was supported in part by a grant from the American Heart Association, and it was done during Dr. Sasyniuk's tenure of a Post-doctoral Fellowship from the Medical Research Council of Canada.Dr. Sasyniuk's present address is Department of Pharmacology, Mayo Clinic, Rochester, Minnesota 55901.Received August 26, 1970. Accepted for publication November 3,1970. tive route exceeds the refractory period of the path to be reentered. The difficulty in this hypothesis is that the refractory period of cardiac tissue, particularly in the ventricles, is so long. All the above requirements can be met with relative ease in the mammalian A-V node where conduction velocities of about 0.02 m/sec have been demonstrated. However, it is questionable whether propagation over an alternative route in the ventricles could be slow enough to permit reexcitation of elements with such a long refractory period. Wallace and Mignone (2) were able to produce reentrant extrasystoles in the ventricles only by cooling a discrete area of the left ventricle sufficiently to produce unidirectional block at the junction of the warm a...

The functional refractory periods (FRP) of auricular and ventricular muscle, and of the A-V transmission system were estimated in the denervated dog heart. In all three tissues the FRP was found to be a curvilinear function of the immediately preceding cycle length, with values for all but very early premature beats falling close to the curve describing the basic cycles; that is, there was no evidence for a cumulative effect of frequency. In the auricle, the FRP of even the earliest possible premature beats appeared to fit the curve relating cycle length to refractory period. In both the A-V node and ventricles very early responses deviated from an otherwise smooth relationship. It is postulated that the deviations may represent dissociation of the properties of two different elements in each of these tissues.