A model of one-dimensional action potential propagation was used to compare activation times and recovery times measured from simulated unipolar and bipolar electrograms with the activation and recovery times measured from simulated transmembrane action potentials. Theory predicts that the intrinsic deflection--the time of the maximum negative slope of the unipolar electrogram QRS complex--corresponds to the time of maximum positive slope of action potential depolarization. Similarly, the time of the maximum positive slope of the unipolar electrogram T wave corresponds to the time of maximum negative slope of action potential repolarization. This study showed that the difference between the unipolar electrogram activation time and the action potential activation time and the difference between the unipolar electrogram recovery time and the action potential recovery time were small during ideal conditions of uniform propagation in a long cable. Nonideal conditions, however, were associated with activation time differences in excess of 1.8 msec and recovery time differences in excess of 30 msec (243 msec in certain conditions). Nonideal conditions that had a major influence were changes in activation sequence, propagation in a short cable, and propagation through regions of nonuniform coupling resistance and/or nonuniform membrane properties. Nonideal conditions that had a smaller influence were variations in distance from the measurement site to the simulated tissue surface, nonzero reference potentials, and the addition of distant events. Recovery time differences were more sensitive to the nonideal conditions than were activation time differences, and both depended on the action potential shape. When distant events significantly contributed to the unipolar electrogram waveform, the time differences when bipolar electrograms were used were less than those when unipolar electrograms were used; however, under other conditions, the time differences were comparable. Results showed that activation times and especially recovery times measured from electrograms can be greatly affected by conditions independent of changes in the underlying action potential waveforms.

Computer simulations and isolated tissue experiments were used to characterize the relation between excitability and margin of safety for propagation in anisotropic ventricular myocardium. Longitudinal, uniform transverse, and nonuniform transverse tissue directions were modeled in a one-dimensional Beeler-Reuter based cable. Stimulation threshold was smallest in the nonuniform transverse direction. The safety factor for propagation was determined in the model as the total axial charge that was available for depolarizing downstream tissue divided by the threshold charge that was just sufficient for continued propagation and was largest in the longitudinal direction. The strength-interval plot for the junction between simulated longitudinal and nonuniform transverse directions identified a range of stimulus strengths and intervals that resulted in nonuniform transverse but not longitudinal propagation. When high values of transverse resistance were used, higher stimulus strengths during premature stimulation resulted in longitudinal but not nonuniform transverse propagation. The experimental strength interval plots from 17 L-shaped preparations of isolated sheep epicardial muscles had similar characteristics. In nine additional L-shaped tissue experiments, changing extracellular K' concentration from 4 to 20 mM resulted in progressive membrane depolarization and conduction impairment in both directions. However, in eight of nine experiments, complete block occurred first in the transverse direction. In one experiment, block was simultaneous in both directions. We conclude that, under normal conditions, threshold requirements for active propagation are lower for transverse than for longitudinal propagation. In addition, when active membrane properties are impaired, the safety factor for propagation is Larger in the direction along the longitudinal axis of the cells. (Circulation Research 1990;67:97-110) A ction potential propagation in the heart is a complex function determined by the electrical properties associated with cell excitability,"2 as well as by the degree of cell-to-cell communication and the geometrical arrangements of intercellular connections.3,4 Moreover, conduction velocity in cardiac muscle is faster along the longitudinal (L) axis of the cells than along the transverse (T) axis.5-7 The

Tissue ingrowth is a major impediment to the removal of defibrillation leads implanted in the CS and GCV of sheep. Reduction of tissue ingrowth by coating the shocking coils with ePTFE or by backfilling with MA facilitates transvenous lead removal with reduced tissue trauma.

The relation between nonuniform epicardial activation and ventricular repolarization properties was studied in 14 pentobarbital anesthetized dogs and with a computer model. In 11 dogs, isochrone maps of epicardial activation sequence were constructed from electrograms recorded from the pulmonary conus with 64 electrodes on an 8 X 8 grid with 2-mm electrode separation. The heart was paced from multiple sites on the periphery of the array. Uniformity of epicardial activation was estimated from activation times at test sites and their eight neighboring sites. Acceleration shortened and deceleration prolonged refractory periods. The locations of acceleration and deceleration sites of activation differed during drives from various sites, and differences in uniformity of activation during pairs of drives were correlated to differences in refractory periods (r = 0.76, range 0.59-0.93). In three additional experiments, transmural activation sequence maps were constructed from electrograms recorded from needle-mounted electrodes placed upstream and downstream to epicardial activation delays. Activation proceeded from epicardium to endocardium upstream to the delays and from endocardium to epicardium downstream to the delays. A computer simulation of two-dimensional action potential propagation based on the Beeler-Reuter myocardial membrane model provided insights to the mechanism for the results of the animal experiments. The two-dimensional sheet modeled the transmural anisotropic histology of the canine pulmonary conus and corresponded to previous reports and histology of specimens from five experiments. Simulated activation patterns were similar to those found in the experimental animals. In addition, action potentials were electronically prolonged at sites of deceleration and shortened at sites of acceleration, results comparable to the animal experiments. Our findings demonstrate that the location of areas of nonuniform epicardial activation is dependent on drive site and that nonuniform activation electronically modulates repolarization properties. Therefore it seems likely that the site of origin of ectopic ventricular complexes, especially in ischemic myocardium where activation is nonuniform, could be an important determinant of whether ectopic activity initiates sustained tachyarrhythmias.

Patients with chronic atrial fibrillation (AF) and symptomatic bradycardia often receive ventricular-based pacemakers. However, many of these patients continue to have symptoms of palpitations, which may be due to ventricular rate variability. It has previously been shown that continuous ventricular pacing during AF has a stabilizing effect on the ventricular rate. Hence, a study was initiated to determine whether a patient-specific optimal ventricular standby rate that reduces the ventricular rate variability, without over-pacing, could be predicted. A ventricular rate stabilization (VRS) pacing algorithm that increases the pacing rate until instability is reduced below a threshold was developed. The VRS algorithm was utilized to determine a patient-specific standby rate in 15 patients with chronic AF, intact AV nodal conduction, and implanted pacemakers. The computer algorithm controlled a pacemaker programmer to automatically change the pacemaker's ventricular pacing rate via telemetry. Patients were studied for 15 minutes with VRS and for 15 minutes with 50 ppm fixed rate pacing (control). The results were as follows: (1) VRS versus control = P < 0.05; (2) mean ventricular pacing rate (ppm): 77 +/- 13 versus 50 +/- 0; (3) mean ventricular rate (beats/min): 82 +/- 13 versus 79 +/- 12; (4) ventricular rate coefficient of variation (%): 11 +/- 1 versus 22 +/- 5; (5) percent pacing: 75 +/- 8 versus 6 +/- 8; (6) percent of RR intervals less than minimum pacing interval eliminated: 58 +/- 12; (8) regression analysis: mean VRS pacing rate (beats/min) = 0.96 x mean control ventricular rate + 2.3, r2 = 0.85. We concluded that: (1) a moderate increase in the ventricular pacing rate was required to substantially stabilize the ventricular rate; (2) the resulting mean ventricular rate increased marginally; (3) a majority of RR cycles less than each patient's minimum pacing interval were eliminated; and (4) there was a linear relationship between the mean ventricular rate during control and the optimal ventricular pacing rate. Thus, a ventricular pacing rate close to the mean ventricular rate during control consistently reduced the ventricular variability. Although pacing at an increased ventricular standby rate reduces variability at rest, the optimal solution would likely be an adaptive rate algorithm that changes the ventricular standby rate as the mean intrinsic rate varies.