The effects of procainamide on conduction in anisotropic canine ventricular myocardium.

Abstract

Although conduction velocity in cardiac tissue is dependent on fiber orientation, the influence of commonly used antiarrhythmic agents on conduction longitudinal and transverse to such fibers is unknown. We evaluated the effects of procainamide on conduction velocity and intracellular potentials in vitro during conduction longitudinal and transverse to fiber orientation in epicardial strips obtained from areas of uniform fiber orientation from 15 adult mongrel dogs. Ventricular epicardial strips demonstrated marked anisotropy. At a pacing cycle length of 1000 msec, mean conduction velocity longitudinal to fiber orientation averaged 0.602 + 0.051 m/sec and mean conduction velocity transverse to fiber orientation was 0.186 + 0.024 m/sec, resulting in a ratio of longitudinal to transverse conduction velocities of (OL/T) 3.27 ± 0.38. After the addition of procainamide, conduction velocity decreased to 0.532 + 0.062 m/sec longitudinal to fiber orientation and to 0.174 ± 0.023 m/sec transverse to fiber orientation resulting in a decrease of OL/T to 3.09 ± 0.37 (p < .05 vs control). Before the addition of procainamide, when pacing at progressively shorter cycle lengths, conduction velocity longitudinal to fiber orientation was relatively unchanged, whereas conduction velocity transverse to fiber orientation decreased resulting in an increase in OL/T. After the addition of procainamide, conduction velocity at shorter pacing cycle lengths decreased both longitudinal and transverse to fiber orientation demonstrating the well-known use-dependent effect of procainamide. However, in contrast to control conditions, conduction velocity longitudinal to fiber orientation was slowed by a greater extent than the conduction transverse to fiber orientation, resulting in an even greater decrease in OL/T. To investigate the effect of differences in drug binding during propagation in different directions, we examined conduction velocity during alternations in pacing direction and compared it with velocity during steady-state pacing. At a pacing cycle length of 1000 msec, no difference was observed between the initial conduction velocity after changing pacing directions and the steady-state conduction velocity. At pacing cycle lengths shorter than 1000 msec, when changing from transverse to longitudinal conduction, there was an initial drop in normalized conduction velocity that was present on the first beat of longitudinal conduction; however, with continued pacing in a longitudinal direction there was a further decrease in conduction velocity. We conclude from the above findings that: (1) procainamide has nonhomogeneous effects on conduction in anisotropic ventricular muscle; conduction velocity longitudinal to fiber orientation is depressed by a greater extent than transverse to it; and (2) differences in drug binding depending on propagation direction and/or an effect of procainamide on junctional resistivity may be responsible for the directional differences in the effects of procainamide we observed. Circulation 74, No. 3...

Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy.

“…Reductions in resting membrane potential or in action potential upstroke velocity (Vm,) correspond to lower values ofMf and should result in lower 0L and 0T with no change in 0L/OT (pattern Bl ) according to the model. Experimental interventions that alter these properties, however, have sometimes resulted in pattern B2 (37)(38)(39)(40)(41)(42)(43) as well as Bl (28,44). The model predicts that increases in Cm, Rm, or S produce the Bl pattern ( Fig.…”

Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium.

“…Eight adult mongrel dogs weighing [10][11][12][13][14][15][16] kg were used for these experiments. The dogs were anesthetized with sodium pentobarbital (30 mg/kg i.v.…”

“…(Circulation 1988;78:1478-1494 S low conduction and unidirectional block are requirements for reentrant pathways.1-9 In addition to slow conduction because of a decrease in the rate of rise of the intracellular potential, differences in cell-to-cell coupling and the geometric arrangement of fibers in cardiac tissue may also produce slow conduction. [10][11][12][13][14][15] pathway defined by fixed areas of block could provide a long enough conduction pathway to allow sufficient time for an impulse conducting at a normal velocity to return to fully recovered cardiac tissue. The extent of increased conduction time distal to anatomic barriers in cardiac tissue has not been extensively investigated.…”

Predicting ventricular tachycardia cycle length after procainamide by assessing cycle length-dependent changes in paced QRS duration.

“…Moreover, even in normal uniform anistropic tissue, procainamide suppresses conduction velocity in the longitudinal axis of fiber orientation to a greater extent than in the transverse direction. 12 Thus, differences in wavefronts of activation with a differential effect of procainamide dependent on the wavefront of activation make it unlikely that changes in any index of conduction would be exactly the same under both conditions after procainamide. 12 In addition, there is no reason to believe that the effect of procainamide on conduction velocity is similar in diseased and normal tissue.…”

“…12 Thus, differences in wavefronts of activation with a differential effect of procainamide dependent on the wavefront of activation make it unlikely that changes in any index of conduction would be exactly the same under both conditions after procainamide. 12 In addition, there is no reason to believe that the effect of procainamide on conduction velocity is similar in diseased and normal tissue. Although we found no dilference in the increase in normal and abnormal electrogram duration recorded during sinus rhythm after procainamide administration, it appears that the degree of change in conduction, as indexed by electrogram duration, is greater in chronically infarcted tissue at shorter paced cycle lengths.…”