Mechanism of augmented premature responses in canine ventricular muscle.

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Abstract
Experiments were performed to determine the mechanism inducing paradoxical augmentation of premature action potential (AP). Premature stimuli (S2) were applied to isolated dog ventricular muscle at variable intervals after every 10th-15th driving stimulus (S1) at 0.5-1 Hz. AP (R1 and R2) elicited by S1 and S2 of equal strength and duration were recorded by conventional microelectrode methods. Measurements were made of the amplitude (Amp), duration (APD), plateau area (PA) and maximum rising velocity (.ovrhdot.Vmax) of each AP and the proximity (P), the interval from 90% repolarization point of R1 to S2. In normal K+ solution, R2 had a greater plateau area (PA2) than R1 at P less than 300 ms. PA2 also increases progressively with decreasing P at [Ca2+]o (extracellular Ca2+ concentration) of 0.4, 1.6 and 6.4 mM and reached its maximum at P of 40-90 ms. The maximum .DELTA.PA [(PA2-PA1)/PA1 .times. 100] was estimated at 15 .+-. 9, 28 .+-. 6 and 61 .+-. 11% at each [Ca2+]o; .DELTA.PA increased significantly (P < 0.01) as the [Ca2+]o was increased. Verapamil (10-5 M) suppressed completely the augmentation in the plateau of the premature AP. Experiments in high K+ (21 mM)-high Ca2+ (6.4-10 mM) solutions revealed that the Amp, APD and .ovrhdot.Vmax of R2 were greater than those of R1. They progressively increased with a reduction of the S1-S2 interval, as did the plateau of the premature AP at normal [K+]o (extracellular K+ concentration). Apparently augmented Ca2+-influx may be triggered by a very premature depolarization in canine ventricular muscle, in contrast to the concept that recovery from inactivation of the Ca2+ current is delayed in mammalian heart muscle.