kBSTRACT A custom-made probe, consisting of four electrodes arranged so that two orthogonal )ipolar electrograms could be recorded from a single site, was used to record epicardial activity during itrial and ventricular pacing in five normal and five anesthetized open-chest mongrel dogs with nyocardial infarction. Unfiltered bipolar electrograms recorded with a 2 mm interelectrode distance iveraged 36 + 15 mV in amplitude and 16 5 msec in duration in normal areas and 14 ± 11 mV and 13 ± 12 msec in infarcted areas (p < .01 infarct vs normal). The bipolar electrograms were vector ,ummed so that a vector loop could be generated at each site. The direction of epicardial impulse )ropagation as determined by multipoint isochronal activation mapping was compared with that ndicated by maximum x,y deflection of the vector loop. At 203 sites (141 normal and 62 infarcted) :here was a median error of only 13 degrees and an excellent correlation by linear regression (r2 = .95).[n normal myocardium vector loops were straight (60%), open (21%), or hooked (19%). In infarcted Tnyocardium, notched and irregular loops were occasionally seen. However, a clear maximum x,y leflection was still obtained from 98% of infarcted sites. During ventricular pacing in normal dogs, iniform epicardial conduction was observed for up to 4 cm longitudinal to fiber orientation but only 1 -m transverse to it. At selected sites longitudinal to fiber orientation conduction velocity was 0.618 n/sec, electrogram duration 12 msec, and vector amplitude 76 mV compared with 0.304 m/sec, 18 nsec, and 38 mV during conduction transverse to fiber orientation (p < .05 for all comparisons). Vector mapping of epicardial activation was performed during ventricular tachycardia induced by )rogrammed stimulation in two of five 2-week-old canine myocardial infarcts. Aside from minor .rregularities caused by impulse spread around areas of block, vector loops indicated when impulses were spreading away from the area of early epicardial activity and thus directed mapping to the region f earliest activation. We conclude that vector loops generated by summing orthogonal local bipolar -lectrograms accurately represent the direction of epicardial activation in both normal and infarcted Tnyocardium. Such loops may prove useful in mapping tachycardias and in clarifying details about :ardiac activation processes. Circulation 74, No. 3, 603-615, 1986. MAPPING of the sequence of ventricular activation with single or multiple epicardial, transmural, or endocardial electrodes has provided basic information about the mechanism and origin of both experimental and clinical arrhythmias.'-1 However, a limitation of these studies is that they either require sophisticated recording techniques with expensive computerized analysis systems3' 6 or large numbers of recording sites using a single probe electrode to define areas such as the site of origin of ventricular tachycardia (VT

To evaluate autonomic influence on arrhythmogenesis in an animal preparation of triggered activity, we gave increasing doses of cesium chloride (0.125 to 5.0 mmol/kg iv) to 24 dogs distributed equally among four protocols of autonomic intervention: control, total denervation, beta-blockade, and left stellate stimulation. All dogs underwent atrioventricular node ablation followed by ventricular pacing. A left ventricular endocardial monophasic action potential (MAP) catheter allowed for detection of "MAP early afterdepolarizations" (mEAD). mEAD amplitude was measured relative to MAP amplitude. Cesium chloride (CsCl) increased both MAP duration (132% after 0.125 mmol/kg to 188% after 1.0 mmol/kg; p less than .001) and mEAD amplitude (20% after 0.125 mmol/kg to 49% after 1.0 mmol/kg; p less than .001) in a dose-dependent fashion. All dogs exhibited ventricular ectopy at roughly equivalent doses (0.88 +/- 0.5 mmol/kg). Cesium's peak effect on MAP characteristics, sinus node automaticity, and systolic blood pressure coincided with the onset of sustained ventricular tachycardia (VT). Whereas control and denervated dogs developed VT after similar doses of CsCl (1.21 +/- 0.1 vs 1.12 +/- 0.14 mmol/kg; p = NS), none of the six beta-blocked dogs developed sustained VT. Conversely, those dogs having undergone stellate stimulation developed VT after smaller doses (0.58 +/- 0.34 mmol/kg; p less than .001) and with earlier onset (12 vs 30 sec; p less than .025). After 0.5 mmol/kg of CsCl, left stellate stimulation augmented relative mEAD amplitude compared with control (51% vs 38%; p less than .001), whereas beta-blockade had little effect (39% vs 38%; p = NS). Autonomic intervention as such can affect the arrhythmogenicity of CsCl and similarly alter MAP characteristics. Furthermore, as beta-blockade can prevent sustained arrhythmia without eliminating mEADs, autonomic tone appears to modulate the expression of mEADs as sustained VT.

Amiodarone therapy leads to a significant impairment in myocardial conduction, yet it causes only a modest decrease in the maximum rate of depolarization of the action potential (dV/dT). To determine whether the decrease in dV/dT solely accounts for the impaired myocardial conduction or whether passive membrane properties may also be involved, we studied 21 ventricular epicardial tissues from 14 beagles; six dogs received long-term treatment (3-6 weeks) of amiodarone orally, and the remaining dogs served as controls. Amiodarone therapy was associated with a decrease in conduction velocity (0.41 ± 0.15 vs. 0.56 ± 0.05 m/sec; p<0.01). There was a trend toward a decrease in dV/dT and a significant decrease in the space constant (0.69 ± 0.27 vs. 1.05 ± 0.25 mm; p = 0.01), of which the latter correlated closely with the decrease in conduction velocity measured in the amiodarone-treated tissues (r= 0.85, p<0.05). These data indicate that the decrease in myocardial conduction velocity caused by amiodarone is primarily due to effects on overall resistance to passive current flow rather than effects on the inward sodium current. (Circulation 1988;78:684-691) Amiodarone is singularly effective in the treatment of malignant ventricular tachyarrhythmias. In patients with ventricular tachycardia refractory to other antiarrhythmics, there is a 50-80% response rate to amiodarone. '-11 The mechanism of amiodarone's antiarrhythmic action is unknown. Ventricular tachycardia likely results from reentrant circuits that rely on critical interactions between the conduction characteristics and refractoriness of the myocardium. Pharmacological alterations of these interactions effect an antiarrhythmic (or proarrhythmic) response. Amiodarone

Twenty-eight anesthetized mongrel dogs were studied 2 to 74 months after experimental myocardial infarction in order to examine the effects of procainamide, lidocaine and acetylstrophanthidin on conduction within the infarcted region and the way such effects relate to changes in body surface potentials and antiarrhythmic efficacy. In each animal, 100 to 200 QRS complexes in the X, Y, Z leads were signal averaged, vector summed and high pass filtered at 50 Hz. Susceptibility to ventricular arrhythmia was evaluated using routine programmed ventricular extrastimulation in the anesthetized open chest animal. Epicardial electrograms were sequentially recorded at 45 standard sites within the infarcted region and referenced to the beginning of the QRS complex. Of the three agents, only procainamide exhibited antiarrhythmic action whereas lidocaine and acetylstrophanthidin produced inconsistent effects. Procainamide prolonged the time at which activity in the epicardial electrographic recordings ended relative to the beginning of the body surface QRS complex. This effect was significantly greater in electrograms that ended late in the QRS complex in the control state than for those that ended earlier. Such preferential effect on more abnormal sites was reflected on the body surface as a greater effect of procainamide in prolonging the lower energy terminal portion of the signal-averaged QRS complex than the earlier high energy portion. In contrast, lidocaine significantly prolonged the time at which electrograms ended only for those relatively normal electrograms that ended early in the QRS complex in the control state. In the signal-averaged body surface QRS complex, lidocaine produced a small but significant prolongation of the early high energy portion of the QRS complex but no change in the late portion. Acetylstrophanthidin produced a significant prolongation in early-ending electrograms and, surprisingly, significantly shortened the end time of electrograms that ended late in the QRS complex in the control state. Such effects were not reflected, however, on the body surface because acetylstrophanthidin had no significant effect on either the early or the late portion of the QRS complex. It is concluded that procainamide's differential effect between early- and late-ending electrograms is detected on the body surface by a greater prolongation in the terminal portion of the QRS complex. The signal-averaged body surface QRS complex is less sensitive in detecting the more subtle effects on conduction caused by lidocaine and acetylstrophanthidin.(ABSTRACT TRUNCATED AT 400 WORDS)

We studied a group of 17 dogs 4 to 6 years after infarction produced by 2 hr occlusion of the anterior descending coronary artery followed by reperfusion. Dogs in this "late" infarct group were compared with a group of 24 dogs with "early" healed infarcts (2 to 24 weeks old). With signal-averaging techniques body surface potentials were recorded during sinus rhythm. After thoracotomy epicardial electrograms were recorded from 45 standardized sites within the infarcted region and characteristics of selected electrograms were compared with anatomic features of underlying myocardium. Epicardial recordings from the late infarct group demonstrated earlier local activation (p< .001) and shorter electrogram duration (p< .001) when compared with recordings from the early infarct group. There was less temporal dispersion of activation and electrogram duration among the 45 sites in dogs with late infarcts as measured by respective coefficients of variance (p= .007 and <.001). With programmed stimulation six dogs in the late and eight in the early infarct group exhibited inducible sustained ventricular tachycardia. Mean cycle length of the tachycardia in dogs with late infarcts was significantly shorter (p = .035). Late potentials were notably less prominent in dogs in the late infarct group with ventricular tachycardia than in dogs in the early infarct group. Fewer abnormal electrophysiologic characteristics of late infarcts coincided with relatively less scar in the underlying myocardium. Moreover, the strength of electrophysiologic-anatomic correlations differed in late as opposed to early infarcts. The latter findings suggest long-term evolution of infarct anatomy. We conclude that a substrate for reentrant tachycardia is present in dogs 4 to 6 years after reperfused infarction. Conduction characteristics are less abnormal in these late healed infarcts and are associated with a shorter ventricular tachycardia cycle length and less pronounced late potentials on the body surface.