Joseph F. Spear

Influence of Brief Vagal and Stellate Nerve Stimulation on Pacemaker Activity and Conduction within the Atrioventricular Conduction System of the Dog

Experiments were performed on open-chest anesthetized dogs to determine the quantitative effects of autonomic nerve stimulation on pacemaker activity and conduction. The lead II electrocardiogram together with bipolar electrograms were recorded from the atria, the His bundles, and the ventricles. The vagi or the stellate ganglia were stimulated in dogs which exhibited either sinus rhythm, ectopic atrial rhythm, junctional rhythm, or ectopic ventricular rhythm. The time courses of the change in heart rate in response to vagal or stellate stimulation were characteristic for each type of rhythm. The characteristic responses of different cardiac pacemaker sites to autonomic influence were demonstrated to be important factors in the production of wandering pacemakers and in the emergence of ectopic beats. Sinus pacemaker activity was more sensitive to modification by autonomic stimulation than was atrioventricular (AV) conduction. However, subliminal autonomic effects on AV transmission were brought out during conduction of premature atrial beats, thereby demonstrating a coupling interval dependency of autonomic influences on AV conduction. The present experiments also showed how fluctuations in autonomic activity could result in Mobitz type II second-degree heart block, pseudosupernormal conduction, and the concertina effect observed in the preexcitation syndrome.

Supernormal Excitability and Conduction in the His-Purkinje System of the Dog

The electrophysiological characteristics of the period of supernormal excitability and supernormal conduction were investigated in the isolated canine His-Purkinje system. Strength-interval curves were determined as the minimum transmembrane current required to bring the impaled fiber to threshold potential following a conducted action potential. During the period of supernormal excitability, 17.0 ± 4.6% (SD) less current than that required during diastole was needed to reexcite fibers throughout the left and right bundle branch-Purkinje system. A period of supernormal excitability was not found in the His bundle proximal to its pseudobifurcation or in ventricular muscle. The period of supernormal excitability was voltage dependent in the bundle branch-Purkinje system; it began during phase 3 at full repolarization (88.8 ± 5.6 [SD] mv) and reached minimum current requirements at about 74.3 ± 5.8 mv. Action potentials evoked during this period were conducted faster than they were during diastole. The maximum rates of depolarization of these supernormally conducted action potentials were not greatly depressed compared with control rates. A period of supernormal conduction was not observed in the His bundle. When the external potassium concentration was increased from 2.7 mM to 5.0 um or 7.5 mM, both the supernormal period of excitability and the period of supernormal conduction were eliminated in Purkinje fibers.

Effect of Lidocaine on the Ventricular Fibrillation Threshold in the Dog during Acute Ischemia and Premature Ventricular Contractions

The effect of lidocaine on the ventricular fibrillation threshold was investigated in the anesthetized open-chest dog during paced supraventricular rhythm, during acute ligation of the anterior descending coronary artery, and during premature ventricular contractions. The minimum current (in milliamperes) required to induce ventricular fibrillation was determined by passing a train (100 Hz) of 10-14 constant-current pulses through ventricular epicardial electrodes during the vulnerable period of the cardiac cycle. Lidocaine was administered intravenously either as a sudden injection or as a “loading’ injection followed by a constant infusion. Following a single injection of 0.7 mg/kg the blood lidocaine decreased to half its original arterial concentration in 9 min. After the termination of a 50-60-min constant drip of 70 &mgr;g/kg/min which was preceded by a loading injection of 2 mg/kg, the blood lidocaine concentration fell to 50% of its original value in 31 min. Lidocaine at therapeutic blood levels (1.2-5.5 &mgr;g/ml) increased the fibrillation threshold during paced supraventricular rhythm and reversed the fall in fibrillation threshold accompanying acute myocardial ischemia and premature ventricular contractions. The present studies quantify the ability of lidocaine to reduce the vulnerability of the heart to fibrillation during supraventricular rhythm, acute ischemia, and premature ventricular beats and provide information concerning the metabolism of lidocaine in the anesthetized dog.

Effect of current pulses delivered during the ventricular vulnerable period upon the ventricular fibrillation threshold

The effect of current delivered to the myocardium as either a pulse or train of pulses upon the recovery of excitability and upon the subsequent threshold for initiating ventricular fibrillation was studied in open chest dogs. Bipolar epicardial electrodes delivered current during the vulnerable period, and a circular array of six electrodes surrounding the central current electrode recorded the time course of recovery of myocardial excitability. Increasing the current intensity of either a pulse or train of pulses at the central site increased the temporal dispersion in recovery of excitability among the six peripheral electrode sites. This increase in temporal dispersion was associated with a decrease in ventricular fibrillation threshold immediately after the application of current. The degree of temporal dispersion in recovery after the train was increased by coronary occlusion but decreased by administration of lidocaine. Increasing the intensity of current delivered during the vulnerable period increases the degree of inhomogeneity in recovery of the myocardium until a level is attained that allows multiple asynchronous reentry and fibrillation. Interventions that increase or decrease the intrinsic amounts of inhomogeneity in the myocardium modify the amount of “extra inhomogeneity” that the current pulses must add during a fibrillation threshold determination to bring the myocardium to a level for fibrillation. In this way current delivered during the vulnerable period assesses vulnerability to fibrillation. These experiments also suggest that the ventricular fibrillation threshold following premature ventricular beats evoked by malfunctioning cardiac pacemakers may be lower than that following spontaneously occurring premature beats at the same coupling interval.

Localization of Ventricular Irritability by Epicardial Mapping Origin of Digitalis-Induced Unifocal Tachycardia from Left Ventricular Purkinje Tissue

Epicardial mapping technics were used to locate the origin of ventricular ectopic beats produced by pacing and by the administration of ouabain and acetylstrophanthidin in pentobarbital-anesthetized open-chest dogs. The sequence of epicardial depolarization was determined with close bipolar reference and roving electrodes. The wave of excitation spread in concentric manner from driven points with the origin having the earliest time. Nonparasystolic unifocal ventricular tachycardia (UVT) was then aroused in nine dogs with ouabain or acetylstrophanthidin. Plunge electrodes were inserted for recording and stimulating of bundle of His and Purkinje fibers. Earliest epicardial ventricular activation of the UVT beats always occurred at or near the apex of the left ventricle. Purkinje fiber (PF) spikes from the region of earliest epicardial depolarization appeared just prior to ventricular activation. Pacing at this point produced QRS configuration almost identical to that during UVT. His bundle pacing normalized QRS configuration and suppressed UVT. Isolated right ventricular and left ventricular PF were perfused in the same tissue bath for microelectrode impalement. Infusion of ouabain increased the rate of automatic discharge of left ventricular PF before those from the right ventricle in each of five preparations. These studies suggest that digitalis-induced unifocal ventricular tachycardia originates below the His bundle from Purkinje tissue supplying the left ventricle and demonstrate that automaticity of canine PF from the left ventricle is preferentially enhanced by ouabain.

The effects of coronary artery disease on the ventricular fibrillation threshold in man.

The ventricular fibrillation threshold (VFT) was measured in 28 patients at the time of cardiac surgery. The VFT was measured with a 100 Hz train of 24 rectangular pulses positioned across the ST segment and T wave. Current was applied to the epicardial surface of either ventricle with a bipolar electrode probe. In six patients, the normal right VFT was 24.3 ± 5.2 mA, and in 10 patients the normal left VFT was 33.6 ± 9.5 mA (p < 0.05). In 12 patients with > 75% obstruction of the left anterior descending coronary artery, the left VFT was 18.6 ± 6.9 mA. This value was significantly less than the left VFT in patients without coronary artery disease (p < 0.001). This study shows that the VFT can be measured in man and that coronary artery disease reduces this parameter.

The mechanism of apparent right bundle branch block after transatrial repair of tetralogy of Fallot.

The electrocardiographic pattern of right bundle branch block (RBBB) is routinely observed after transatrial repair of tetralogy of Fallot even though no ventriculotomy has been performed. The mechanism of this conduction disturbance was studied in 16 patients with tetralogy of Fallot and one patient with infundibular pulmonic stenosis. Preoperative ECGs and vectorcardiograms showed right ventricular hypertrophy and no RBBB. Epicardial activation maps were obtained before and after total surgical repair in all patients and after infundibular resection but before closure of ventricular septal defect (VSD) in four of these patients. After infundibular resection, RBBB appeared and activation was markedly delayed (> 30 msec) over the pulmonary outflow tract, but was unchanged over the body of the right ventricle. No further changes in ventricular activation occurred after closure of the VSD. This study shows that RBBB after transatrial repair of tetralogy of Fallot is usually produced by infundibular resection, but not by VSD closure, and is associated with delayed activation of the pulmonary outflow tract and base of the right ventricle which results from damage to portions of the right ventricular conduction system.

Quantitative study of the effect of lidocaine on the threshold for ventricular fibrillation in the dog

Abstract The effects of lidocaine upon the current required to induce ventricular fibrillation was assessed during normal supraventricular rhythm and after premature ventricular beats. Ventricular fibrillation thresholds were determined by passing a train of 10 to 15 constant current pulses, each 4 msec in duration, at 10 msec intervals through ventricular epicardial electrodes during the vulnerable period. The intensity of the current pulses was varied, and the ventricular fibrillation threshold was defined as the current in milliamperes which caused ventricular fibrillation. Our data show that during administration of lidocaine the ventricular fibrillation threshold after both normal and premature beats increased; that is, fibrillation was more difficult to evoke in the presence of lidocaine. Over a range of 0 to 6¦μ¦g/ml the ventricular fibrillation threshold increased in direct proportion to the increase in blood level of lidocaine. The time courses describing the change in ventricular fibrillation threshold and the blood levels of lidocaine correlated directly with each other. The half-life for the disappearance of lidocaine from the blood was 32 minutes. These studies describe the metabolism of lidocaine in the anesthetized dog and quantify the ability of lidocaine to reduce the vulnerability of the heart to fibrillation.

The Effect of Changes in Rate and Rhythm on Supernormal Excitability in the Isolated Purkinje System of the Dog A Possible Role in Re-entrant Arrhythmias

Microelectrode techniques were used to investigate the effects of rate and rhythm changes upon the period of supernormal excitability during repolarization in isolated canine right and left bundle branch and Purkinje fibers. The same microelectrode was used for both intracellular stimulation and recording. Excitability curves (strength-interval curves) were measured as the minimum depolarizing current required to re-excite the fiber during repolarization of a conducted action potential. During the supernormal period it required an average of 17.0 ± 4.6 SD % less than diastolic current to re-excite the fibers throughout the left and right bundle branch-Purkinje system. The supernormal period of excitability in the bundle branch-Purkinje system was voltage dependent, reaching minimum current requirements at 74.3 ± 5.8 SD mV. Excitability curves of conducted action potentials were determined at basic cycle lengths ranging from 1000 to 300 msec and following single and multiple premature beats. The decrease in action potential durations associated with shorter cycle lengths was not accompanied by a corresponding shortening of the supernormal period of excitability. Therefore, at shorter cycle lengths the supernormal period encompassed a greater proportion of the total action potential; in some cases as much as 50% of the total action potential duration exhibited a period of supernormal excitability. The supernormal period of excitability could be eliminated by perfusing the tissues in elevated potassium (5.0 and 7.5 mM) Tyrodes solution. The possible implications for the generation of re-entrant arrhythmias are discussed.

The Effects of Digitalis Glycosides on the Ventricular Fibrillation Threshold in Innervated and Denervated Canine Hearts

Digitalis glycosides have been implicated in increased vulnerability to ventricular fibrillation in man. In order to investigate the genesis and occurrence of ventricular fibrillation in the presence of digitalis, the effects of both acetylstrophanthidin and ouabain on the ventricular fibrillation threshold (VFT) were studied in the open-chest anesthetized dog. The current required to induce ventricular fibrillation was determined by passing a train of 12 constant current pulses through epicardial electrodes during the vulnerable period of the cardiac cycle. It was found that an intravenous bolus infusion of acetylstrophanthidin (0.050-0.097 mg/kg) or ouabain (0.035-0.075 mg/kg) in intact innervated dog hearts raised the VFT from 40% to 260% above control values. Continuous infusions of acetylstrophanthidin to toxic levels also resulted in an elevated VFT. Vagotomy alone did not qualitatively change the effects of acetylstrophanthidin on VFT. However, following vagotomy and stellate sympathectomy, infusions of both toxic and subtoxic doses of acetylstrophanthidin resulted in a decrease in the VFT from 40 to 80% below control values. In denervated animals in which the peripheral ramifications of the left stellate ganglion nerves were stimulated, the VFT decreased below control values in the absence of acetylstrophanthidin, but during stellate stimulation in the presence of acetylstrophanthidin the VFT was increased above control values. These studies demonstrated that the increase in VFT by digitalis in the healthy, innervated heart was mediated via an associated increase in sympathetic activity; in the absence of neural influences digitalis decreased the VFT.