Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model.

OBJECTIVE: Previous studies have attempted to characterise the genesis of triggered activity related to early afterdepolarisations. Little is known about their conduction behaviour. This study was designed to examine the origin and conduction behaviour of triggered activations to throw light on the pathogenesis of torsade de pointes. METHODS: Electrophysiological interactions related to triggered activations and early afterdepolarisations between papillary muscle and Purkinje fibres were studied in the guinea pig in a single chambered bath. EDTA (5 mM) in Tyrode's solution was used and microelectrodes were placed in both papillary muscle and Purkinje fibres. RESULTS: During early superfusion, marked prolongation of action potential duration and early afterdepolarisations occurred in Purkinje fibres but not in papillary muscle. In addition: (1) with prolongation of action potential duration and early afterdepolarisations in Purkinje fibres, triggered activations arose during phase 2 and were conducted to papillary muscle, where they induced activations; (2) the number of papillary muscle discharges increased with the increase in Purkinje fibre action potential duration in a linear correlation; (3) severing a segment of papillary muscle from Purkinje fibres eliminated these papillary muscle activations; (4) some triggered activations did not conduct to papillary muscle; these had smaller amplitude, slower rate of depolarisation (dV/dt), more positive activation voltage, and similar peak voltages compared to conducted triggered activations; (5) a low plateau resulting from electrotonic interaction was recorded at the Purkinje fibre-papillary muscle junction; this plateau may have facilitated conduction of triggered activations. CONCLUSIONS: In this preparation there was a disparity of effect on Purkinje fibre and papillary muscle. Prolongation of action potential duration and repetitive activations due to early afterdepolarisations originated in Purkinje fibres and were conducted to papillary muscle. Purkinje fibre-papillary muscle interactions are of interest in relation to torsade de pointes arrhythmias which are believed to arise from this mechanism.     

The role of canine superficial ventricular muscle fibers in endocardial impulse distribution.

Thin sections of canine right and left ventricular endocardium and myocardium were studied in a tissue bath to compare conduction properties of intraventricular specialized conducting tissue [Purkinje fibers (PF)], the superficial layers of subendocardial ventricular muscle (SVM), and the deeper ventricular muscle (DVM) below this level. The study was carried out because of observations that some areas of the endocardium, which are devoid of either specialized conducting tissue or of PF-VM junctions between specialized conducting tissue and ventricular muscle, conduct relatively rapidly, favoring specific orientations of propagation. Preparations containing PF, SVM, and DVM were studied electrophysiologically and histologically. A technique of stripping limited areas of endocardium was used to expose DVM in order to determine its intrinsic calculated conduction velocity. In 12 preparations, the average calculated conduction velocity in PF was 1.62 m/sec, and the average in DVM was 0.26 m/sec. The SVM conduction velocity was intermediate between the two, averaging 0.98 m/sec when propagation was parallel to SVM fiber orientation. Conduction velocity transverse to SVM fiber orientation was not significantly different from DVM conduction velocity. Histologically, the most superficial layers of VM were oriented uniformly in the direction of rapid subendocardial conduction, in contrast to DVM fibers in which orientation varied. It is concluded that the geometric arrangement of SVM fibers may provide a means for rapid subendocardial conduction and impulse distribution at a conduction velocity intermediate between PF and DVM in areas devoid of specialized conducting tissue.     

Electrophysiological consequence of skeletal myoblast transplantation in normal and infarcted canine myocardium.

OBJECTIVE: The purpose of this study is to test our hypothesis that injection of skeletal myoblasts (SkMbs) into viable tissue may alter impulse conduction but that injections into nonviable tissue (scar) will have negligible impact. BACKGROUND: Myocardial infarction (MI) is a major public health problem. SkMb transplantation after MI has been shown to have some beneficial effect on hemodynamic function. Previous studies have indicated that SkMbs do not electrically couple with viable host myocardium in vivo. METHODS: We used optical mapping to measure impulse propagation and arrhythmia inducibility in the canine left ventricular wedge preparation with and without MI. MI was created by temporary ligation of a branch of the left anterior descending coronary artery (LAD) (7.0 +/- 3.8 ng/mL troponin 24 hours after MI). Labeled SkMbs (10(8) in 4 mL of serum-free basal solution) were injected from the epicardium (20-40 0.1 mL injections) into normal myocardium (n = 8) or the central zone of the MI (n = 6). RESULTS: During endocardial pacing in the absence of MI, transmural conduction velocity was similar with (35.75 +/- 3.4 cm/s) and without (37.42 +/- 3.6 cm/s) SkMb transplantation. However, pacing from the epicardium resulted in conduction slowing in regions that were DiI-positive and associated with the expression of skeletal myosin (fast) but not connexin-43. In all preparations with MI (n = 13), abnormal impulse propagation was seen regardless of SkMb transplantation. Arrhythmias (at least one extra beat after standard programmed stimulation) occurred most frequently in preparations with MI independent of SkMb transplantation. In preparations without MI (n = 8), SkMb transplantation did not significantly increase arrhythmia inducibility. CONCLUSION: We conclude that SkMbs transplanted into normal myocardium can cause abnormal impulse propagation. These data suggest that the location of SkMb transplantation may influence arrhythmia vulnerability associated with MI.     

Mechanisms of triggered activity induction at the border zone of normal and abnormal cardiac tissue

Ionic mechanisms that may be involved in inducing triggered activations at the border zone (BZTAs) of normal and abnormal Purkinje fiber segments were investigated. In a two-chamber bath, fibers were divided into a normal segment and segment treated with ethylenediaminetetraacetic acid to stimulate electrophysiologic alterations 24 hours after infarct. Interventions to normal segments included 1.8 mM lidocaine (n = 10), 3 × 10⁻⁴ mM tetrodotoxin (n = 5), 10⁻³ mM aconitine (n = 4), 3 mM cesium chloride (n = 7), 10⁻² mM verapamil (n = 4), and 6–8 mM (n = 7) of K⁺. Ethylenediaminetetraacetic acid (3.3 mM) prolonged action potentials and induced low diastolic potentials in the normal segment border zone. Tetrodotoxin, lidocaine, and high K⁺ levels suppressed BZTAs; cesium chloride and aconitine increased BZTAs; and verapamil did not reduce BZTAs. The finding that BZTAs were not abolished by verapamil suggests that abnormal automaticity is not a mechanism. Apparently, BZTAs depend on the Na⁺ inward current activated by depolarization of the membrane secondary to depolarization of adjacent cells.     

Effects of lidocaine on hypoxic and ischemic cardiac cells

Cardiac cells severely affected by ischemia or hypoxia were exposed to lidocaineine in vitro while intracell and extracell potentials were recorded. Endocardial preparations dissected from normal dog hearts were superfused with physiologic solutions of low oxygen content until myocardial cells were partially depolarized and generated poor action potentials. Purkinje fibers were slightly altered. Epicardial preparations dissected from infarcted dog hearts to Include both normal and ischemic regions were superfused with physiologic solutions of normal oxygen content. The ischemic cells were partially depolarized and generated poor action potentials. In both types of preparations, conduction was very slow and irregular but abnormal automaticity was not observed with intracell recordings. However, abnormal spontaneous firing occurred. Lidocaineine in therapeutic concentrations (1.1 or 2.2 × 10^?5 molar) invariably abolished propagated action potentials in severely affected cells and modestly reduced membrane responsiveness in cells that were nearly normal. Concomitantly, abnormal spontaneous beats disappeared with exposure to lidocaine. The recovery of responsiveness of abnormal cells was greatly prolonged by lidocaine and strength-interval curves were shifted upward and to the right. Tetrodotoxin (5 × 10^?7 g/ml) markedly depressed or abolished the action potentials of the severely affected cells. It is concluded that lidocaine abolished abnormal spontaneous beats by extinguishing very slow conduction resulting from depressed fast channels.     

Rate-related suppression and facilitation of conduction in isolated canine cardiac Purkinje fibers

Previous studies have shown that antegrade conduction through damaged His Purkinje tissue may be suppressed following rapid ventricular pacing (overdrive suppression of conduction). We studied this phenomenon using isolated Purkinje fibers placed in a three-chamber bath. Superfusates for the left, middle, and right segments of the fiber were altered to produce action potentials that resembled those of normal bundle branch, damaged His bundle, and normal His bundle, respectively. To produce anisotropic conduction, the left segment of the fiber was adjusted to be three to four times longer than the right segment. Pacing the right segment at intermediate rates produced maximal action potential amplitude in the middle segment and 1:1 right-to-left conduction, whereas pacing at faster or slower rates reduced action potential amplitude and produced block. Pacing the left segment at fast or slow rates also reduced action potential amplitude in the middle segment, but conduction was maintained (anisotropy). After rapid or slow left segment pacing, action potential amplitude in the middle segment remained low during subsequent right segment pacing at intermediate rates, and transient block occurred (overdrive or underdrive suppression of conduction). With time, action potential amplitude normalized and conduction resumed. In other more severely depressed preparations, conduction block occurred even at intermediate right segment pacing rates prior to left segment pacing. Under these conditions, pacing the left segment at intermediate rates increased action potential amplitude in the middle segment and temporarily permitted 1:1 conduction at intermediate right segment pacing rates (overdrive facilitation of conduction).(ABSTRACT TRUNCATED AT 250 WORDS)     

Symposium on the management of ventricular dysrhythmias. Concept of reentry versus automaticity

Arrhythmias can result from abnormal impulse initiation or conduction. Abnormal initiation results from either automaticity or triggered activity. Enhanced automaticity may be due to a normal automatic mechanism (a normal property of the sinus node and specialized conducting fibers) or to an abnormal mechanism such as automaticity in depolarized fibers. Triggered activity is caused by afterdepolarizations that occur either during repolarization (early afterdepolarization) or after repolarization is complete (delayed afterdepolarization). Triggered activity due to delayed afterdepolarizations is dependent on critical heart rates. Overdrive pacing may distinguish between normal and abnormal automaticity. Antiarrhythmic drugs can alter arrhythmias that result from abnormal impulse initiation. To suppress an arrhythmia resulting from abnormal impulse generation, a drug may (1) suppress the abnormal automatic mechanism, i.e., specific effect on ionic current; (2) suppress afterdepolarizations; (3) depress conduction in tissue surrounding automatic focus; or (4) modify refractory period of tissue in and around automatic focus. Abnormal impulse conduction results in reentrant excitation. Conditions necessary for reentry include a combination of unidirectional block and slowed conduction. A reentrant mechanism can be determined by an anatomically defined circuit or solely by the functional properties of the tissue (leading circle mechanism). Circus movement reentry around an anatomic obstacle may respond to antiarrhythmic drugs differently from reentry caused by a leading circle mechanism. Initiation and perpetuation of a reentry mechanism depends on a delicate interplay between conduction velocity and duration of the functional refractory period in the reentry circuit.(ABSTRACT TRUNCATED AT 250 WORDS)     

心肌致密化不全患者的常规心电图及心律失常分析

目的回顾性分析心肌致密化不全患者的体表心电图异常改变和心律失常发生情况。方法选择心肌致密化不全患者103例,对体表心电图、动态心电图及心律失常进行分析。结果 101例(98.1%)患者存在不同程度的心电图异常。窦性心律91例(88.3%),持续心房颤动12例(11.7%)。患者多表现P波异常、各种传导阻滞、QRS波起始切迹(类△波)、终末切迹、R波递增不良、异常Q波、ST段下移、T波双向、倒置。患者以室性心律失常多见,室性期前收缩占58.3%,室性心动过速占50.5%,4例发生心室颤动。结论体表心电图是心肌致密化不全的重要异常表现之一,主要特征表现为P波异常、各种传导阻滞、QRS波起始切迹(类△波)、终末切迹、异常Q波及ST-T改变。心律失常类型多样,以室性心律失常多见。     

Lidocaine and Nisoldipine Attenuate Almokalant-Induced Dispersion of Repolarization and Early Afterdepolarizations In Vitro

Attenuation of Almokalant-Induced Proarrhythmias In Vitro. Introduction: Treatment with Class III antiarrhythmic agents may lead to increased dispersion or repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na⁺ or Ca²⁺-blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro. Methods and Results: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent almokalant (0.1 μM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33%± 4.2%, n = 18) than in the VM (17%± 5.9%, n = 18. P < 0.05). In six of the preparations, addition of 1, 5, and 25 μM lidocaine reduced the almokalant-induced prolongation in a concentration-dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 μM lidocaine, the remaining prolongation was 7%± 12.2% (P < 0.05 vs time controls) in the PF and 14%± 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 μM nisoldipine did not reduce the almokalant-induced prolongation in the PF and VM, hut attenuated the spike-and-dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with almokalant (0.3 and 1 μM, respectively) at an API) of 828 ± 41.4 msec. In six separate preparations pretreated with lidocaine (5 μ) the almokalant-induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 μM) did not influence the response to almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear. Conclusion: At concentrations that did not affect the APD in the VM hut reduced the APD in the PE. lidocaine suppressed almokalant-induced dispersion and the development of EADs. Nisoldipine, (m the other hand, inhibited almokalant-induced EADs directly. Hence, (he primary APD-prolonging effect of a Class III agent may he preserved, but the risk of proarrhythmary reduced, during concomitant treatment with low concentrations of a Na⁺- or Ca²⁺ blocking agent.     

Endocardial catheter mapping in patients in sinus rhythm: relationship to underlying heart disease and ventricular arrhythmias

Catheter mapping during sinus rhythm was performed in 132 patients with coronary artery disease and 26 patients with congestive noncoronary cardiomyopathy. Each of the patients had a clinical history of one of the following: no ventricular arrhythmia, nonsustained ventricular tachycardia, cardiac arrest, or sustained ventricular tachycardia. The characteristics of the endocardial electrogram and other measured indexes of slow endocardial conduction were compared between patients with different types of disease and in different arrhythmia groups to determine if differences existed. The cardiomyopathic group had a higher percent of normal endocardial electrograms than the coronary artery disease group, with no evidence of slow endocardial conduction. The sustained ventricular tachycardia group exhibited a greater percent of abnormal endocardial electrograms and more evidence of slow endocardial conduction, distinguishing this group from the three other arrhythmia groups. We conclude the following: The underlying electrophysiologic substrate varies in patients with different ventricular arrhythmias. It is therefore inappropriate to analyze all patients with ventricular arrhythmias as a single group. Patients with congestive noncoronary cardiomyopathy, regardless of the type of their arrhythmia, have a relatively normal endocardium. Those patients with serious ventricular arrhythmias should not be considered candidates for surgery directed at removing abnormal endocardium.     

Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation

BACKGROUND: Rapid firing within pulmonary vein sleeves frequently initiates atrial fibrillation. The role of the autonomic nervous system in facilitating spontaneous firing is unknown. OBJECTIVES: The purpose of this study was to determine if autonomic nerve stimulation within canine atrium and pulmonary vein sleeves initiates arrhythmia formation. METHODS: Extracellular bipolar and intracellular microelectrode recordings were obtained from isolated superfused canine pulmonary veins (N = 28) and right atrium (N = 5) during local autonomic nerve stimulation. RESULTS: Autonomic nerve stimulation decreased pulmonary vein sleeve action potential duration (APD90 = 160 +/- 17 to 92 +/- 24 ms; P < .01) and initiated rapid (782 +/- 158 bpm) firing from early afterdepolarizations in 22 of 28 pulmonary vein preparations. The initial spontaneous beat had a coupling interval of 97 +/- 26 ms. Failure to induce arrhythmia was associated with a failure to shorten APD90 (151 +/- 18 to 142 +/- 8 ms; P = .39). Muscarinic receptor blockade (atropine: 3.2 x 10(-8) M) prevented APD90 shortening in 8 of 8 preparations and suppressed firing in 6 of 8 preparations, whereas beta1-adrenergic receptor blockade (atenolol: 3.2 x 10(-8) M) suppressed firing in 8 of 8 preparations. Suppression of the Ca transient with ryanodine (10(-5) M) completely suppressed firing in 6 of 6 preparations. Inhibition of forward Na/Ca exchange by a transient increase in [Ca+2]o completely suppressed firing in 4 of 6 preparations. The same stimulus trains produce atropine-suppressed APD90 shortening in superfused right atrial free wall but fail to produce triggered arrhythmia. CONCLUSIONS: The data demonstrate triggered firing within canine pulmonary veins with combined parasympathetic and sympathetic nerve stimulation. Both an enhanced Ca transient and increased Na/Ca exchange may be required for arrhythmia formation.     

Alpha 1-adrenoceptor regulation of delayed afterdepolarizations and triggered activity in subendocardial Purkinje fibers surviving 1 day of myocardial infarction.

Alpha 1-adrenoceptor agonists were shown to induce delayed afterdepolarizations (DADs) and triggered activity in the presence of elevated extracellular Ca2+. We investigated the effects of alpha 1-adrenoceptor stimulation on DADs and triggered activity in canine Purkinje fibers that survived 1-day of myocardial infarction. Endocardial preparations were studied using standard microelectrode techniques. In quiescent preparations showing no DADs and in presence of propranolol (2 x 10(-7) M), phenylephrine (10(-6) M), an alpha 1-adrenoceptor agonist induced DADs (n = 6) and differentially induced triggered activity in ischemic but not in normal Purkinje fibers (n = 4). In 8 preparations that showed subthreshold DADs, phenylephrine increased the DAD amplitude from 4.0 +/- 2.5 mV to 8.0 +/- 3.3 mV (P less than 0.03) and from 3.2 +/- 1.5 mV to 6.5 +/- 3.7 mV (P less than 0.05) at paced cycle lengths of 800 and 400 ms, respectively. Phenylephrine caused subthreshold DADs to reach threshold and result in triggered activity (n = 6). The effects of phenylephrine were abolished by 10(-6) M prazosin, an alpha 1-adrenoceptor blocker. Our results suggest that alpha 1-adrenoceptor stimulation regulates DADs and triggered activity seen in subendocardial Purkinje fibers surviving 1 day of myocardial infarction and may contribute to the spontaneous ventricular tachycardia seen in vivo at this stage.     

Treadmill exercise testing in the Wolff-Parkinson-White syndrome

Graded treadmill exercise testing was performed in 54 patients with the Wolff-Parkinson-White syndrome and preexcitation (persistent in 36, intermittent in 9 and concealed in 9). Forty-eight patients had previous paroxysmal supraventricular arrhythmia (spontaneous or induced or both). At initiation of treadmill testing, the nine patients with intermittent and the nine with concealed preexcitation had normal conduction. None manifested preexcitation during exercise. Thirty-six patients had preexcitation at initiation of exercise; exercise produced no change in preexcitation in 2, partial normalization of the QRS complex in 16 (due to enhanced atrioventricular [A-V] nodal conduction), and total normalization of the QRS complex in 18 (due to enhanced A-V nodal conduction in 14 and to rate-dependent anomalous pathway block in 4). Exercise-provoked block of the anomalous pathway reflected prolonged anomalous pathway refractoriness, as measured with atrial stimulation. All 18 patients with either total or partial preexcitation at peak exercise manifested more than 1 mm flat or downsloping S-T segment depression. None had evidence of ischemic heart disease. None of the 54 patients manifested either paroxysmal supraventricular tachycardia or atrial fibrillation during or after treadmill exercise.Treadmill exercise testing in patients with preexcitation frequently produces partial or total normalization of the QRS complex due to enhanced A-V nodal conduction and, less commonly, total normalization due to rate-dependent block of the anomalous pathway. False positive S-T segment changes (suggesting ischemia) are always present in patients manifesting preexcitation during treadmill testing. Treadmill exercise testing in patients with preexcitation does not provoke paroxysmal supraventricular tachycardia or atrial fibrillation and is not useful as a provocative test for arrhythmia.     

His bundle recordings in bradycardia-dependent AV block induced by premature beats.

Symptomatic bradycardia-independent atrioventricular block occurred in a patient with right bundle-branch block, left anterior hemiblock, and prolonged HV interval. The arrhythmia, triggered by a spontaneous or induced premature beats, appeared when the post-extrasystolic PP and HH intervals increased to a critical value. Reinitiation of atrioventricular conduction required the presence of ventricular escapes. Bradycardia-dependent atrioventricular block was related to either an enhanced or slightly rising slope of diastolic depolarization, or to a decrease in membrane responsiveness. The patient also, most probably, had tachycardia-dependent atrioventricular block. Both types of conduction disturbance occurred in the same part of the intraventricular conducting system, either in the low His bundle or left bundle-branch or its posteroinferior division. It is suggested that the electrophysiological study of cases with prolonged HV intervals should include procedures which can expose bradycardia-dependent atrioventricular block.     

Role of the AV node and adrenergic stimulation in initiation of fascicular and atrioventricular nodal tachycardias--a case report

Fascicular tachycardia is an uncommon form of left ventricular tachycardia in young patients with normal heart. Ventriculo-atrial conduction during VT is usually absent. Retrograde conduction was observed in a 14-year old boy with left posterior fascicular VT (LPF-VT) triggered by exercise. During isoproterenol infusion, atrial stimulation induced a cascade of arrhythmias--echo, pair or runs of AVNRT and fascicular tachycardia triggered by fascicular beats. Also, during infusion LPF-VT was initiated spontaneously. After successful ablation of VT, sustained typical AVNRT was inducible. Finally, ablation of slow pathway of AV node was performed. After ablation,no arrhythmia was inducible following isoproterenol and exercise.     

Suppression of autonomic-mediated triggered firing in pulmonary vein preparations, 24 hours postcoronary artery ligation in dogs

INTRODUCTION: Rapid arrhythmia originating within pulmonary veins (PVs) precipitates atrial fibrillation (AF) in man. To determine a possible basis for an increased incidence of AF observed peri-myocardial infarction in man, we compared AF induction in vivo and triggered arrhythmia formation within isolated PVs in vitro in normal dogs and dogs studied 24 hours postcoronary artery ligation. METHODS AND RESULTS: The incidence of AF initiated by atrial premature stimuli was increased in dogs postcoronary artery ligation (6/9) versus normal (2/12) (P = 0.03). In isolated PVs from normal hearts, pause-dependent early afterdepolarizations (EADs) were enhanced by catecholamines. Rapid arrhythmia (1,182 +/- 213 beats/min) was triggered during isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 16/23) using the same pacing pauses eliciting EADs. Rapid arrhythmia (802 +/- 161 beats/min) was also triggered by local autonomic nerve stimulation (ANS; N = 18/23). Despite equivalent pause-dependent afterdepolarization formation in PVs from infarcted hearts, a rightward 45-fold and 28-fold shift in the dose-response curve for afterdepolarization enhancement was observed for isoproterenol and norepinephrine, respectively (P < 0.02). ANS (N = 1/19) and isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 0/9 and 0/12, respectively) (P = 0.0001) failed to elicit arrhythmia formation. Beta-adrenergic receptor desensitization was associated with a 2.5-fold increase in PV beta-adrenergic receptor kinase (ARK). CONCLUSION: The data demonstrate decreased susceptibility of isolated canine PVs for arrhythmia triggered by local ANS, or pacing pauses in the presence of a catecholamine + acetylcholine, postmyocardial infarction, despite a greater susceptibility of the intact heart to AF. The decreased arrhythmia susceptibility was observed coincident with an increase in beta-ARK and a decreased responsiveness to beta-adrenergic receptor agonists.     

Electrical and contractile behavior of large intestinal musculature of piebald mouse model for Hirschsprung's disease

These studies were directed toward better characterization of the abnormalities of motor function in the large intestine of mutant mice with congenital aganglionosis and megacolon. Analysis of pressure-volume relations in the megacolon and aganglionic terminal segment showed increased intestinal wall compliance in the dilated colon and reduced wall compliance in the aganglionic region as compared to normal littermates. Migrating contractile complexes occurred spontaneously in ganglionated regions of the large intestine of both normal and mutant mice, but never propagated into the aganglionic segment of the abnormal bowel. Tetrodotoxin eliminated the migrating complexes and increased random spontaneous contractions in all areas except the aganglionic region. Circular muscle tension was reduced by electrical field stimulation, and poststimulus rebound contractions occurred in all ganglionated regions of the intestine of both normal and mutant mice. No responses to electrical stimulation occurred in the aganglionic segments of the preparations from mutant mice. The poststimulus responses "fatigued" at a faster rate in the megacolonic region of the abnormal bowel than in the equivalent region of the normal bowel, when evoked repetitively over prolonged time periods. There were no differences between the intestines of normal and mutant mice in latency, amplitude, duration, or area under the contractile curves of the poststimulus responses. Intracellular electrical recording from circular muscle fibers revealed slow depolarizing potentials with action potentials at the crests in all regions of the large bowel from both normal and abnormal mice. It also showed excitatory and inhibitory junction potentials in response to electrical stimulation. Inhibitory junction potentials summated during repetitive stimulation and postinhibitory rebound excitation occurred after offset of the stimulation. Stimulus-evoked junction potentials were recorded in all regions of the large intestine except in the aganglionic segment of the mutant mice. We concluded that most of the electrical and mechanical behavior of the aganglionic terminal segment reflected the absence of inhibitory innervation of the musculature in this region.     

Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ.

STUDY OBJECTIVE--The aim of the study was to assess the influence of general anaesthesia on electrocardiographic and arrhythmogenic responses to left anterior descending coronary artery occlusion. DESIGN--Pigs weighing 18-20 kg were anaesthetised with alpha chloralose 100 mg.kg-1 (n = 9) or thiopentone 30 mg.kg-1 (n = 9) and the arrhythmogenic effects of coronary artery occlusion were examined by sequential electrocardiographic measurements every 5 min and arrhythmia analysis every minute over a 60 min period. RESULTS--alpha Chloralose predisposed to lower ST segment elevation (analysis of variance for repeated measurements p less than 0.002), less marked epicardial conduction delay (p less than 0.01) with slower progression to monophasic potentials, and in contrast, to a greater number of episodes of ventricular premature beats (p less than 0.005), ventricular tachycardia (51 v 32 episodes), and ventricular fibrillation (6 v 2 pigs) than barbiturate anaesthesia. CONCLUSIONS--alpha Chloralose and barbiturates exerted opposite electrocardiographic and arrhythmogenic effects in a porcine model of acute myocardial ischaemia. Due to its proarrhythmic effect chloralose should probably be used in studies dealing with spontaneous and induced ischaemic arrhythmias.     

The relationship between ventricular arrhythmias and ischemia-induced conduction delay in closed-chest animals within 24 hours of myocardial infarction

To investigate the myocardial conduction characteristics of premature impulses during the first 24 hours following coronary ligation and its relationship to late infarction ventricular arrhythmias, transmural electrodes were positioned in the normal and ischemic myocardium in nine dogs. Cardiac conduction in ischemic myocardium was delayed 15 minutes post coronary occlusion both in the epicardium and endocardium, both in the anterograde (base to apex) and retrograde (apex to base) direction, and was maintained at the same level throughout the experiment. Conduction across the border of ischemic myocardium from ischemic to the normal segment was also delayed, especially in the endocardium. Spontaneous ventricular arrhythmias recorded on Holter tapes showed significant increase in the number of premature ventricular complexes and ventricular tachyarrhythmias 9 hours after infarction. Thus our findings suggest that spontaneous arrhythmias occurring in the late phase of acute myocardial infarction (AMI) are independent of the ischemia-induced conduction delay and an alternate mechanism such as abnormal automaticity may be responsible for late ventricular arrhythmias.     

Paroxysmal nonreentrant tachycardias due to simultaneous conduction in dual atrioventricular nodal pathways.

Electrophysiologic studies were performed in a 41 year old man for analysis of paroxysmal tachycardias appearing in various electrocardiographic patterns of supraventricular and ventricular bigeminy, junctional and ventricular tachycardia and atrial fibrillation, among others. All these arrhythmias were due to dual atrioventricular (A-V) nodal pathways with simultaneous dual fast and slow conduction of single atrial beats at a normal basic sinus rate. Moderate changes in sinus rate and in fast or slow pathway conduction times, or both, changed the position of the slowly conducted beats between the neighboring two fast conducted beats and resulted in various electrocardiographic manifestations of the conduction disturbance. Different blocks, such as second degree type 1, 2:1, 3:1 and possibly also type II, in one of the two pathways and occasionally aberrant conduction induced even more unusual tracings. After intravenous injection of 25 mg of ajmaline, unexpected lengthening and shortening of the A-H interval occurred, suggesting variable shifts between fast and slow pathway conduction. The incidence of dual A-V nodal pathways is discussed; it was documented in 17 (4.2 percent) of 405 patients studied. A theoretical model of A-V nodal conduction is proposed to explain its normal properties and abnormal patterns.