Kalman Greenspan

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Conventional intracellular recordings from the bundle of His and right bundle branch of the canine heart demonstrated that the slope of diastolic depolarization is markedly depressed by superfusion with relatively small concentrations (4−8 μg/ml) of acetylcholine. As the cells become less automatic, take-off potential increases, rise time of phase 0 is reduced, action potential amplitude increases, and conduction proceeds more rapidly.

Effect of Cycle-Length Alteration upon the Configuration of the Canine Ventricular Action Potential

Action potentials recorded from canine ventricular fibers displayed characteristic alterations in configuration upon abrupt change in the cycle length. After a relative prolongation of the diastolic interval, abbreviation of phase 2 and slowing of phase 3 were consistently observed, while a relative shortening of diastole was terminated by an action potential displaying prolongation of phase 2 and a steeper phase 3. Neither circumstance was attended by a consistent alteration in action potential duration. The more conventional view, directly relating duration of phase 2 to the length of the preceding diastole, clearly does not obtain immediately following an abrupt alteration of cycle length. This cycle-length-dependent phenomenon may account, in part, for the post-extrasystolic T-wave alterations observed in the human electrocardiogram. It is also consistent with the clinical observation that such T-wave changes may occur without premature contractions, requiring only a relative prolongation of the R-R interval. Evidence is also presented which relates electrical alter-nans of the T wave to this interval-dependent phenomenon. This characteristic change in action potential configuration occurs under the same temporal circumstances that others have associated with potentiation of contractility. It is therefore suggested that these inotropic phenomena and changes in action potential configuration may relate to alterations in membrane permeability.

T wave alternans: An association with abrupt rate change

Abstract A case of alternation of T wave with reversal of polarity, independent of any changes of the QRS but apparently greatly influenced by abrupt cycle length change, is presented. Evidence suggests that this phenomenon is indicative of severe myocardial disturbance.

The Relation of Contractile Enhancement to Action Potential Change in Canine Myocardium

Simultaneous recordings of contractile tension and transmembrane potentials from canine ventricular tissue yielded a consistent correlation of action potential (AP) alteration with contractile change associated with abrupt rate change. The AP terminating a relative prolongation of the cycle-length manifested shortening of phase 2 with lengthening of phase 3 and was associated with potentiation of contractile force. Conversely, the AP terminating a relative abbreviation of cycle-length displayed a broader phase 2 with a more precipitous phase 3, while the associated contraction was less forceful than the control. In each circumstance, the relative magnitude of cycle-length change correlated with the extent of both AP change and contractile alteration. Changes in AP configuration may reflect changes in transmembrane flux of K+ during repolarization consistent with the findings of prior workers who have related K+ efflux to increased contractility. Mechanical alternans, in addition, was frequently observed in association with abrupt rate change and was consistently associated with an electrical alternans manifested by action potentials with alternately wide and narrow plateaus (phase 2). As above, the more forceful contractions were associated with action potentials which displayed a narrower phase 2. Mechanical alternans initiated by abrupt rate change may represent an adaptive phenomenon prior to the establishment of a stable contractile state, as reflected by a stable AP configuration.

Electrophysiologic correlate of exit block

Abstract Electrophysiologic studies using canine and human tissue confirm, by direct recordings at the cellular level, the existence of exit block produced by artificial pacemakers and shed some light on the mechanism of the exit block. Both human ventricular and canine Purkinje or ventricular tissue, or both, demonstrated Wenckebach structure from the stimulus electrode to the recorded action potentials. This conduction depression was induced by hypoxia, digitalis or infusion of 4 times the normal concentration of potassium (10.8 mEq/liter). Both the exit block and the Wenckebach structure of the block recorded in these experiments are analogous to those seen in clinical situations. In addition, electrophysiologic evidence for unidirectional block is presented.

Complete atrioventricular block due to potassium.

Intravenous infusion of KC1 at a rate of 1.22 or 2.45 mEq per minute to anesthetized dogs frequently resulted in complete A-V block at a time when P waves were still recorded in the ECG. Furthermore, some of the observations suggest that in hyperkalemia a regular idioventricular rhythm may not be essential for the diagnosis of complete atrioventricular (A-V) block. Thus, with complete A-V block induced during a rapidly changing plasma K+, the ventricular pacemaker may be irregular. In addition, evidence was obtained that some parts of the atrial tissue, the automatic ventricular focus and the ventricular myocardium, are more resistant to K+ than is the A-V conduction tissue. The relative sensitivity of the various tissues of the heart seems to depend, among other factors, on the rate of KCl infusion.

Asynchrony of Conduction within the Canine Specialized Purkinje Fiber System

Asynchrony of conduction may prove to be an important mechanism for reentrant arrhythmias. The purpose of these experiments was to explore asynchronous conduction in the distal branches of the canine Purkinje system. Microelectrodes were placed in Purkinje bundle preparations resembling a T configuration, thereby permitting assessment of differential conduction times induced by premature beats (S2). Equal conduction depression was observed in the post extrasystolic beat (S1 at wide coupling intervals (S2-S1). Asynchrony of conduction was frequently observed in response to narrow coupling intervals. These differential conduction times induced disparities of activation times greater than 50 msec. In fibers exhibiting preferential depressed conduction, local block was observed with further decrease in the coupling interval. Disparities of activation times at very short S2-S1 coupling times could be markedly increased by minimal decrease in coupling intervals (in the order of 1 to 5 msec). Conduction depression was not clearly dependent upon the level of “take-off” potential or action potential duration. Asynchronous conduction may thus be induced by narrow coupling of premature beats and could account for reentry.

Electrophysiologic studies on Wenckebach structures below the atrioventricular junction.

Abstract Recent clinical reports have suggested that conduction disturbances of the Wenckebach type occur below the atrioventricular junction. The purpose of this study was to demonstrate this type of conduction delay within the canine specialized Purkinje fiber system and human ventricular tissue. Conventional microelectrode techniques were utilized in these experiments. Wenckebach periods with 4:3 conduction occurred within the His bundle in response to hyperkalemic (10.8 mEq/liter) Tyrode infusion. Impalement into the false tendons of the right and left bundle demonstrated typical 5:4 and 3:2 interelectrode Wenckebach periods after administration of nicotine. Similar studies were performed in the distal specialized conducting system where microelectrodes were impaled in a terminal Purkinje cell and ventricular cell. With the administration of acetylstrophanthidin and subsequent development of automaticity, beats conducted in orthograde fashion demonstrated typical 3:2 Wenckebach conduction while maintaining 1:1 stimulated retrograde conduction. When human ventricular tissue was exposed to Tyrode solution containing 4 × normal potassium (10.8 mEq/liter), conduction times from the stimulating to recording electrodes demonstrated 4:3; 3:2 and, finally, 2:1 Wenckebach conduction. These experiments demonstrated the electrophysiologic evidence for Wenckebach structures at all levels of the canine His-Purkinje system and human ventricular muscle.

Relationship Between Potassium and Vagal Action on Atrioventricular Transmission

The relationship between the effects of potassium and vagal stimulation on transmission through the atrioventricular transmission system was investigated. It was observed that infusion of isotonic potassium chloride alleviated atrioventricular block induced by vagal activity. This occurred at plasma potassium levels ranging from 4.8 to 6.9 mEq/liter. This antagonism does not appear to be mediated by catecholamine release since infusion of epinephrine (0.23 μg/min) did not relieve the block. At plasma levels higher than those capable of inhibiting vagal action, potassium enhances parasympathomimetic actions on A-V transmission and, at still higher levels, potassium is capable of inducing A-V block which is independent of the vagus.

An Electrophysiologic Correlate of Ouabain Inotropy in Canine Cardiac Muscle

Action potentials were recorded via intracellular microelectrodes, together with recordings of isometric-contractile tension, from isolated trabecular muscles of canine ventricle. The effects of administration of ouabain solution in concentrations varying from 1.7 × 10−7 to 5 × 10−4 M were recorded. The early inotropic effects of ouabain (increase in contractile force) were accompanied by changes in configuration of the action potential identical to those associated with interval-dependent potentiation in the control state, that is, abbreviation of phase 2 and lengthening of phase 3, without significant change in duration of the action potential. The progressive administration of ouabain, while associated with contractile enhancement of the regularly stimulated contraction was also accompanied by a loss of the contractile increment associated with poststimulation potentiation; this loss of interval-dependent potentiation corresponds to a loss of interval-dependent alteration of the action potential. Thus, both interval-dependent contractile potentiation and ouabain inotropy correlate consistently with phase 2 abbreviation of the accompanying action potentials.