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Previous studies have shown that the toxic effects of cardiac glycosides are not manifested uniformly throughout the myocardium. The purpose of our study was to determine whether cardiac glycosides exert different effects on the right vs. left peripheral Purkinje systems and to ascertain mechanisms involved. Control in vitro measurements of paired right and left canine Purkinje fibers showed higher spontaneous rates in left (24.2 +/- 1.75 beats/min) than in right (11.6 +/- 1.55 beats/min, P less than 0.01, n = 81) Purkinje fiber bundles. Following overdrive stimulation, left Purkinje fiber bundles also showed earlier escape beats. After ouabain exposure (2 X 10-7 M), left Purkinje fiber bundles showed earlier signs of toxicity in 20 of 28 experiments, as determined by changes in the maximum diastolic potential, the degree of diastolic depolarization, spontaneous escape intervals, and the magnitude of delayed after-depolarizations. The enhanced sensitivity of left Purkinje fiber bundles was independent of the extracellular potassium concentration and glycoside polarity, and was also observed in situ. We conclude that distal Purkinje fibers are functionally dissimilar and that the left Purkinje system shows greater sensitivity to cardiac glycosides than the right Purkinje system. These data also support the observation that digitalis-induced dysrhythmias arise in the left ventricle.

Data from numerous experimental infarction studies indicate that rapid myocardial cell depolarization following ischemia causes the flow of injury currents. These currents were measured in the canine myocardium by monitoring voltage gradients across infarct boundaries using silver chloride plunge electrodes, followed by placement of a 100 omega resistor between the electrodes and again measuring the voltage gradients. Current flow was calculated from these measurements with the following results: 1) TQ currents developed within 15 seconds after occlusion and persisted for 120 to 150 minutes, often attaining a magnitude of 1 microA. 2) ST currents also developed within 15 seconds and attained 2 to 3 microA within 15 to 30 minutes, then usually subsided to some degree. 3) T currents were biphasic and attained 2 to 5 microA. Initially, current flowed from normal to ischemic myocardium but usually reversed within 30 minutes after occlusion. 4) The current flow was often disproportionate to the voltage gradient between 120 and 180 minutes after occlusion, possibly indicating electrical uncoupling of the infarcting cells from normal cells. These data indicate that intramyocardial current flow develops early after acute coronary occlusion. These currents may be sufficient to induce reexcitation.

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Previous in situ studies have implicated differences in the pacemaker rates between the left and right ventricular conduction system. Our studies were conducted to characterize automaticity in peripheral right and left canine Purkinje fibers in vitro. Standard microelectrode techniques were utilized. In paired right (RPF) and left (LPF) canine Purkinje fibers, control intrinsic rate (IR) was found to be higher in LPF (24.8 +/- 1.7 beats/min) than in RPF (11.5 +/- 1.5 beats/min, P less than 0.01). Following overdrive stimulation at various cycle lengths, LPF consistently showed earlier escape beats. In low K0+ (1.35 mM), IR increased comparably in both RPF and LPF. However, high K0+ (5.4 mM) resulted in a greater reducton of the IR in RPF (-78%) than in LPF (-58%). After epinephrine (10(-6) M) the IR of LPF > RPF although the chronotropic response was more pronounced in RPF. Adrenergic stimulation preceded by beta-adrenergic blockade did not produce significant differences in the intrinsic rate between RPF and LPF. These findings indicate that automaticity in right and left Purkinje strands is functionally dissimilar.

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