Ronald R. Hope

Re-entrant ventricular arrhythmias in the late myocardial infarction period. 1. Conduction characteristics in the infarction zone.

Dogs 3–7 days following ligation of the anterior descending coronary artery represented a remarkably stable model for re-entrant ventricular arrhythmias (RVA) and allowed detailed electrophysiologic studies of the re-entrant mechanism. In these dogs, we could regularly illustrate the presence of continuous electrical activity originating from the infarction zone (IZ) and bridging the diastolic interval between the initiating and re-entrant beats as well as between consecutive re-entrant beats. Conduction in the IZ was highly complex, with multiple potentially re-entrant pathways, functionally dissociated areas, and areas of localized ventricular confibrillation. Conduction disorders in ischemic myocardium were consistently tachycardia-dependent with the spontaneous onset of RVA specifically associated with a Wenckebach-like conduction pattern in a potentially re-entrant pathway. Both manifest and concealed reentry, as well as re-entrant beats with regular extrasystolic grouping, constant or variable coupling, uniform, multiform and bidirectional QRS configurations, were related to characteristic conduction patterns in the IZ. In summary, the study provides the first direct in vivo evidence of ventricular re-entry and demonstrates propensity for RVA and sudden death in the late myocardial infarction period.

Characterization and Localization of Ventricular Arrhythmias Resulting from Myocardial Ischemia and Infarction

Electrocardiograms and electrograms were recorded in 18 dogs anesthetized with sodium pentobarbital. Using endocardial and epicardial plunge wire electrodes in normal and ischemic or infarcted areas, activation of Purkinje and regular muscle tissue was studied within the first 20–30 minutes and 24 hours after anterior descending coronary artery ligation. The ventricular arrhythmias in the first 20 minutes were abolished during vagally induced atrial arrest, but ventricular automaticity was unchanged from that during the control period. These rate-related arrhythmias were uniformly associated with marked diminution and delay of epicardial activation in the ischemic zone. Slowing of the heart rate caused recovery of the timing, form, and duration of these epicardial potentials with the coincident disappearance of ventricular arrhythmias. The ventricular arrhythmias of the early phase spontaneously subsided with time 20–30 minutes after ligation; concurrently, epicardial activation in the ischemic zone improved. The ventricular arrhythmias noted 24 hours after coronary artery ligation were revealed by vagally induced atrial slowing and suppressed by rapid atrial pacing, indicating the existence of enhanced ventricular automaticity. There was a loss of endocardial muscle activation; Purkinje tissue was depressed but viable in the infarcted zone. The sequence of firing during many of the multifocal ventricular ectopic beats showed that the earliest activation arose from Purkinje tissue in the infarcted zone. However, other ectopic beats appeared to arise from infarcted epicardial muscle.

Re-entrant ventricular arrhythmias in the late myocardial infarction period. 2. Patterns of initiation and termination of re-entry.

The electrophysiologic mechanisms for the initiation and termination of re-entrant ventricular arrhythmias (RVA) were critically analyzed in dogs 3-7 days following ligation of the anterior descending coronary artery, utilizing direct recordings of the re-entrant pathway (RP) from the epicardial surface of the infarction zone. Re-entry could occur during a regular cardiac rhythm if the heart rate is within the narrow critical range during which conduction in a potentially RP exhibits a Wenckebach-like (W) pattem with a beat-to-beat increment of conduction delay until the activation wavefront is sufficiently delayed to re-excite normal myocardium. If a regular cardiac rhythm is associated with limited conduction delay in a potentially RP, premature beats within a critical range of coupling intervals could result in sufficient conduction delay to induce re-entry. Re-entrant ventricular arrhythmias may be unmasked on abrupt termination of a critical fast rate of cardiac pacing only if pacing was terminated during those beats of a W pattern associated with marked conduction delay in a RP. RVA could be ended by one or more properly timed premature beats that would pre-excite part of the RP. An electrophysiologic mechanism for Ron-T and its relationship to onset of ventricular fibrillation was shown, based on markedly delayed RP conduction of the beat prior to the one apparently coupled to the premature beat.

The Pathophysiology of Malignant Ventricular Arrhythmias During Acute Myocardial Ischemia

In 20 anesthetized open-chest dogs, epicardial electrograms were recorded from ischemic and nonischemic zones of the left ventricle during acute occlusion of the left anterior descending artery. The average time to onset of ventricular tachycardia during atrial pacing (150-200 beats/min) was 4 min, 18 sec. In 18 dogs, ventricular ectopic beats were induced in normal and ischemic zones after every tenth atrial stimulus. Those induced in the ischemic zone consistently caused ventricular tachycardia earlier (mean: 3 min, 22 sec) than those in the normal zone (mean: 4 min, 11 sec) (P < 0.01). This arrhythmia, whether spontaneous or induced, always followed the complex which demonstrated the greatest delay of the ischemic zone potential and increased ventricular activation time. Ventricular tachycardia was repeatedly produced by ectopic beats with late diastolic coupling. Analysis of the episodes of tachycardia leading to fibrillation revealed a progressive increase in the ventricular activation time of the successive beats, whereas in those self-terminating episodes ventricular activation time progressively decreased. These data suggest that the major determinant of malignant ventricular arrhythmias in acute ischemia may be the related abnormalities of ventricular activation rather than the coupling of the premature ectopic beats.

Re-entrant ventricular arrhythmias in the late myocardial infarction period. 4. Mechanism of action of lidocaine.

The effect of lidocaine on re-entrant ventricular arrhythmias (RVA) was studied in dogs 3-7 days following ligation of the anterior descending coronary artery; direct recordings were made of the re-entrant pathway (RP) from the epicardial surface of the infarction zone (IZ). Lidocaine in a therapeutic dose consistently prolonged refractoriness of potentially RP(s) in the IZ and produced a higher degree of conduction block at a constant heart rate. Conduction in the adjacent normal zone was not affected. The impairment of conduction induced by lidocaine in the RP was directly related to its ability to abolish re-entrant ventricular beats and tachycardia. Gradual slowing of conduction in the RP consistently developed before abolition: lengthening of coupling of extrasystolic beats in surface leads and gradual slowing of ventricular tachycardia rate occurred. The termination of re-entry was characteristically associated with complete block in the RP. A “selectivity hypothesis” for the antiarrhythmic action of lidocaine is proposed.

The Efficacy of Antiarrhythmic Agents During Acute Myocardial Ischemia and the Role of Heart Rate

The influence of lidocaine, procaine amide, and propranolol on ventricular arrhythmias during acute myocardial ischemia in the dog was examined. Ischemic zone epicardial (IZE) activation delay and the time of onset of ventricular tachycardia (VTt) were studied. Progressive IZE delay always preceded ventricular tachycardia (VT). Ventricular tachycardia occurred when IZE delay extended into the T wave of the standard electrocardiogram but areas of ischemic epicardium were found in which activation delayed beyond the T wave. Fast heart rates during acute ischemia were associated with an accelerated time course of IZE delay and early VT. Slow heart rates resulted in minimal IZE delay and delayed onset or absence of VT. Sympathectomized dogs with heart rates 32% slower than normal dogs did not develop significant IZE delay or VT during ischemia. When heart rates were increased by atrial pacing, these dogs behaved in the same fashion as the normal dogs with respect to IZE delay and VTt. Lidocaine was found to hasten the time course of IZE delay but to have no significant effect on VTt. Procaine amide did not influence IZE delay nor VTt during ischemia. Propranolol slowed the mean heart rate by 20% and appeared to protect against arrhythmia. When the heart rate (115 ± 10 beats/min; mean ± standard deviation) was increased by atrial pacing (184 ± 9 beats/min), propranolol did not significantly influence IZE delay or VTt as compared to the untreated controls. The clinical counterpart of our experiments during acute ischemia may relate to the prehospitalization phase of myocardial infarction.

Re-entrant ventricular arrhythmias in the late myocardial infarction period. 3. Manifest and concealed extrasystolic grouping.

Re-entrant beats with regular extrasystolic grouping were seen in 44% of dogs 3-7 days following ligation of the anterior descending coronary artery. Utilizing direct recordings of the re-entrant pathway (RP) from the epicardial surface of the infarction zone, we found extrasystolic grouping to be based on characteristic tachycardia-dependent conduction disorders in a potentially RP. Trigeminy and quadrigeminy were related, respectively, to a 3:2 and 4:3 Wenckebach-like conduction cycle in a RP. However, quadrigeminy could also be due to an underlying bigeminal rhythm with concealment of alternate re-entrant beats, i.e., concealed bigeminy. A bigeminal rhythm was the result of a 2: 1 conduction pattern in a reentrant pathway with a sufficient degree of conduction delay during the conducted beat of the 2:1 cycle to result in re-entry. A trigeminal or quadrigeminal rhythm could change to a bigeminal rhythm on critical shortening of the cardiac cycle. Fixed and variable coupling were related, respectively, to stable and changing conduction pattern in a re-entrant pathway. On the other hand, extrasystolic grouping could be concealed due to either block in the re-entrant pathway or entrapment in a small area of the closely bordering normal zone.

The Pathophysiology of Tachycardia-dependent Paroxysmal Atrioventricular Block After Acute Myocardial Ischemia Experimental and Clinical Observations

The pathophysiology of paroxysmal A-V block (PAVB) was studied in 20 anesthetized dogs after ligation of the anterior septal artery. Simultaneous recording of leads II and aVR, as well as intracardiac recordings from the His bundle (Hb) and both bundle branches, were monitored. In 18 of 20 experiments, PAVB was localized in the Hb. In all experiments, PAVB occurred subsequent to Mobitz type II A-V block. In eight experiments, PAVB occurred spontaneously during sinus rhythm and was preceded by a period of Wenckebach periodicity superimposed upon a 2:1 A-V block. Vagal-induced slowing of the sinus rate resulted in immediate resumption of 1:1 A-V conduction. In 18 experiments, PAVB was induced by atrial pacing at a critical heart rate in each case (180-300 beats/min). Evidence is presented that A-V conduction was consistently blocked below a critical H-H interval. Slowing the pacing rate, termination of pacinig or increasing the pacing rate until physiological A-V nodal block occurred, all could result in a longer H-H interval and immediate resumption of A-V conduction. When the critical heart rate for PAVB was maintained, a slow idioventricular escape rhythm occurred.Five patients who developed PAVB after acute myocardial ischemia are also reported providing the clinical counterpart for the experimental observations. In all five cases, PAVB occurred on acceleration of the sinoatrial rate (105-140 beats/min) which was spontaneous in two and induced by drugs given for varied therapeutic indications in three (isoprenaline in two and atropine sulfate in one). In all five, PAVB was associated with Mobitz type II and/or 2:1 A-V block. These experimental and clinical observations suggest that PAVB after acute myocardial ischemia appears to be due to a tachycardia-dependent repetitive concealed conduction in the ischemic His-Purkinje system, probably mainly in the Hb. The clinical observations point out potential consequences of a rapid atrial rate in patients with acute myrocarcial ischemia and type II A-V block.

Hierarchy of ventricular pacemakers.

To characterize the pattern of pacemaker dominance in the ventricular specialized conduction system (VSCS), escape ventricular pacemakers were localized and quantified in vivo and in vitro, in normal hearts and in hearts 24 hoars after myocardial infarction. Escape pacemaker fod were localized in vivo during vagally induced atria! arrest by means of electrograms recorded from the His bundle and proximal bundle branches and standard electrocardiographk limb leads. The VSCS was isolated using a modified Ellzari preparation or preparations of each bundle branch. Pacemakers were located by extra- and lntracellu-lar recordings. Escape pacemaker foci in vivo were always in the proximal conduction system, usually the left bundle branch. The rate was 43 ± 11 (mean ± sd) beats/min. After β-adrenergic blockade, the mean rate fell to 31 ± 10 beats/min, bat there were no shifts in pacemaker location. In the infarcted hearts, pacemakers were located in the peripheral left bundle branch. The mean rate was 146 ± 20 beats/min. In isolated normal preparations, the dominant pacemakers usually were in the His bundle, firing at a mean rate of 43 ± 10 beats/min. The rates of pacemakers diminished with distal progression. In infarcted hearts, the pacemakers invariably were in the infant zone. The mean firing rates were not influenced by β-adrenergic blockade. The results indicate that the dominant pacemakers are normally in the very proximal VSCS, bnt after myocardial infarction pacemaker dominance is shifted into the infarct. Distribution of pacemaker dominance is independent of sympathetic influence.

Prolongation of the Q-T interval in lithium toxicity

A patient with lithium intoxication and Q-T prolongation is described. As serum lithium levels fell with therapy, serial electrocardiograms (ECGs) demonstrated T wave changes more commonly associated with lithium. All changes were ultimately reversible.