No abstract

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...

We have measured the E-4031-sensitive repolarization current (IKr) in single ventricular myocytes isolated from rabbit hearts. The primary goal of this analysis was a description of the IKr kinetic and ion transfer properties. Surprisingly, the maximum time constant of this component was 0.8 s at 33-34 degrees C, which is significantly greater than the value of 0.18 s previously reported under similar conditions in the original measurements of IKr from guinea pig ventricular myocytes. The primary, novel feature of our analysis concerns the relationship of the bell-shaped curve that describes the voltage dependence of the kinetics and the sigmoidal curve that describes the activation of IKr. The midpoint of the latter occurred at approximately +10 mV on the voltage axis, as compared to -30 mV for the point on the voltage axis at which the maximum time constant occurred. Moreover, the voltage dependence of the kinetics was much broader than the steepness of the activation curve would predict. Taken together, these results comprise a gating current paradox that is not resolved by the incorporation of a fast inactivated state in the analysis. The fully activated current-voltage relation for IKr exhibited strong inward-going rectification, so much so that the current was essentially nil at +30 mV, even though the channel opens rapidly in this voltage range. This result is consistent with the lack of effect of E-4031 on the early part of the plateau phase of the action potential. Surprisingly, the reversal potential Of /Kr was ~15 mV positive to the potassium ion equilibrium potential,which indicates that this channel carries inward current during the latter part of the repolarization phase of the action potential.

Isolated blocks of dog atrial tissue were dissected to provide a narrow isthmus connecting two broader areas. Unidirectional block was readily demonstrable at the junctions of the narrow band with the larger areas. Transmembrane action potentials just proximal to the blocked junction were abbreviated, while only local electronic potentials were recorded beyond. Acetylcholine restored 1:1 propagation in blocked preparations. The model may explain some of the features of intermittent preexcitation.