ARRYTHMIA Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart

Conduction velocities along longitudinal (vL) and transverse (VT) fiber axes were determined in isolated porcine hearts from subepicardial activation patterns that were produced by local stimulation and measured with a multiterminal electrode. In some of the experiments extracellular [K' ] ([K'].) and transmembrane potentials were recorded. During normal perfusion VL and VT were (cm/sec) 50.08 + 2.13, (SE) and 21.08 0.97. After 3 to 5 min of global ischemia, VL and VT decreased to approximately 30 and 13 cm/sec. Before the occurrence of total inexcitability propagation became time dependent (1) 2: 1 block developed and (2) centrifugal spread from the stimulus site was partially blocked at short intervals and was normal at long intervals. This suggested that slowed conduction was dependent on spatial nonuniformities of recovery from excitability. Slowing of conduction during ischemia was not explained by accumulation of [K+], alone, because VL and VT at a given [K+], were lower during ischemia than during perfusion with elevated K'. In hearts perfused at 20 mM [K+]. "'slow responses" were produced by addition of epinephrine (2.5 x 10-5M). Resting membrane potentials of slow responses were significantly lower than of depressed action potentials during ischemia. The values vL and vT of slow responses (10 and 5 cm/sec) were much lower than the lowest values during ischemia (20 and 10 cm/sec). This indicates that slow conduction in ischemia is associated with depressed action potentials initiated by a partially inactivated rapid Na+ inward current. The time dependence of nonuniform propagation and the relatively high conduction velocities explain two major characteristics of reentrant tachycardias in acute ischemia: (l) the large diameters of reentrant circuits and (2) the beat-to-beat changes in localization of conduction block. Circulation 73, No. 1, 189-198, 1986. THE HIGH INCIDENCE of ventricular tachycardia and ventricular fibrillation is one of the characteristic features of acute, reversible myocardial ischemia.' During these arrhythmias propagation of the cardiac impulse occurs in multiple circus movements and reentrant excitation is responsible for maintenance of recurrent electrical activity.2 The electrophysiologic conditions necessary for these disturbances of cardiac rhythm were described at the beginning of this century.3 In early myocardial ischemia circulating excitation occurs around a zone of block that may be purely functional in nature.2 The dimensions of the circus movements in such a case are determined by the product of conduction velocity and refractory period.4 From the Department of Cardiology and Experimental Cardiology, University of Amsterdam, the Interuniversity Cardiology Institute of the Netherlands, and the Department of Physiology, University of Beme. Supported by the Swiss National Science Foundation, grant 3.958-0.82, and by the Dutch Heart Foundation, grant 83.050. Address for correspondence: A. G. Kleber, Department of Physiology, University of Berne, Buehlplatz 5, CH-3012 Berne, Switzerland. Received July 12, 1985; revision accepted Sept. 19, 1985. Vol. 73, No. 1, January 1986 Slowing of conduction greatly enhances the probability of occurrence of arrhythmias.5 Delayed activation of an ischemic zone indicating a decrease of conduction velocity and/or a change in activation pattern of the ischemic tissue has been noted by many investigators.i-'0 However, conduction velocity was not measured directly. Furthermore, the relationships between the decrease of conduction velocity, the changes in electrical activity at a cellular level,' and ionic shifts, such as accumulation of extracellular K+ 12 are not fully evident. The present experiments were carried out to quantify the changes in conduction velocity of ventricular myocardium during the acute, reversible phase of myocardial ischemia. To account for the effect of tissue anisotropy on conduction, velocities were measured on the longitudinal (vL) and transverse (VT) axis of the cardiac fibers. In some of the experiments epicardial K' concentration was measured simultaneously with VL and VT during ischemia and during perfusion 189 by gest on A ril 6, 2017 http://ciajournals.org/ D ow nladed from