Ectopic Contractions Research Articles

Assessment of electrophysiological mechanisms of ventricular ectopia in arrhythmogenic right ventricular dysplasia

Relevance of the problem. Arrhythmogenic right ventricular dysplasia (ARVD) is one of the significant causes of sudden cardiac death (SCD) among young people. ARVD is characterized by premature ventricular ectopic contractions (PVCs) from the right ventricular outflow tract (RVOT), which may occur before morphological changes appear and, in these cases, it is necessary to assess the risk of developing SCD based on an analysis of the electrophysiological mechanism of the development of PVCs. Purpose of the study. To evaluate the electrophysiological mechanisms of PVCs in patients with ARVD according to stress tests. Material and methods. We examined 13 patients with confirmed ARVD on MRI, including 9 men and 4 women, aged from 26 to 63 years (42.9±11.0). All patients underwent the following studies: standard electrocardiography (ECG), 24-hour ECG monitoring, echocardiography, cardiac MRI, treadmill stress test. During the stress test, at each load level, ventricular ectopy was analyzed (morphology, number of ventricular ectopic complexes), and the dependence of corrected QTc on heart rate was assessed. Results. According to the data obtained, the patients were divided into two groups depending on the response of PVCs to physical activity. The first group – patients in whom the number of PVCs increased during physical activity – stress-induced ventricular ectopy – 10 people (77%). The second group – patients in whom the number of PVCs decreased, or they disappeared at the peak of the load – stress-inhibited ventricular ectopy – 3 people (23%). All patients had a normal reaction of the QT interval to physical activity – its shortening in response to an increase in heart rate. Conclusions. ARVD is characterized by ventricular ectopia from the right ventricle outflow tract or bifocal ectopia from the right ventricle outflow tract and the right ventricle apex. The electrophysiological mechanisms of ventricular ectopia in ARVD are different: the mechanism of trigger activity and increased automaticity.

Estimation of ventricular ectopic beat origin with electrocardiographic imaging

Abstract Background Precise identification of premature ventricular contractions (PVC) origins poses a significant challenge in electroanatomic mapping. Electrocardiographic Imaging (ECGI) allows instantaneous and global activation time mapping, providing a fast way to locate the origin of ectopic contractions. However, the standard methodology to estimate local activation times (LAT) in invasive electrograms is not directly transferable to ECGI signals. Objective In this study, a new methodology to calculate LAT maps with ECGI is presented and compared to the standard method in both, mathematical simulations and patients. Method We conducted computer simulations of five distinct PVCs to generate ECGI signals. Two techniques were applied to estimate LATs: the conventional -dV/dt method, which identifies the steepest negative deflection, and our novel Bayesian approach. The error in the location of the origin of the electrical activation and the similarity of the LAT maps were calculated with respect to the reference computer model. Additionally, we tested both algorithms in four patients with PVCs originated in different locations (three in the output tract of the right ventricle and one in the ventricular base, close the coronary sinus). Results The results indicated a substantial improvement in identifying the earliest activation site using our Bayesian algorithm, with a reduced localization error (1.5 ± 2.5 cm to 0.6 ± 1.5 cm). The root mean squared error (RMSE) was also significantly lower when comparing our Bayesian LAT maps to the reference LATs obtained in the simulations (19.0 ± 5.3 vs. 10.8 ± 4.5 ms). Patient data revealed smoother and more physiologically consistent propagations in the Bayesian maps, aligning with the PVC origins identified via electroanatomical navigation systems. Conclusion This study demonstrates that ECGI signals, when processed with advanced Bayesian techniques, significantly enhance LAT estimation. The proposed methodology improves the localization accuracy of ectopic beats and has practical implications for optimizing PVC treatment protocols.

Impact of Premature Ventricular Complex (PVC) Burden on the Left Ventricle in the Structurally Normal Heart: Hemodynamic Alterations of Idiopathic PVC on Echocardiography.

Premature ventricular complex (PVC) without structural heart disease is mostly viewed as a benign arrhythmia. However, the high burden of PVC causes cardiomyopathy due to intraventricular dyssynchrony. The effects of ectopic contraction on left ventricular (LV) hemodynamics in the structurally normal heart are unclear. To examine the effect of PVC burden on LV dimension, LV systolic function, and intraventricular blood flow, and to determine whether ectopic ventricular contraction affects LV hemodynamics. Patients aged ≥ 18 years with PVC ≥ 5% on Holter recording were enrolled and divided into groups G1 (5-10%), G2 (10-20%), and G3 (≥ 20%). We excluded patients with structural heart diseases, pacemakers, and LV systolic dysfunction [LV ejection fraction (LVEF) < 50%]. Clinical characteristics and routine transthoracic echocardiography parameters were compared. The end-systolic LV internal dimension increased according to the PVC burden from G1 to G3 (p = 0.001). LVEF was inversely associated with PVC burden from G1 to G3 (p = 0.002). The same pattern was seen for LV outflow tract (LVOT) maximal velocity (p = 0.005) and maximal pressure gradient (PG) (p = 0.005), LVOT velocity time integral (VTI) (p = 0.03) and LV stroke volume index (LVSI) (p = 0.008). Systolic function and LV end-systolic dimension were inversely associated with PVC burden. Decreased LVOT flow velocity and PG were related to increased PVC burden. LVOT VTI and LVSI were smaller when the PVC burden exceeded 20%. These negative hemodynamic manifestations of idiopathic PVC were considerable even in structure normal hearts, hence the early elimination of PVC is strongly advised.

Correlation of MRI premature ventricular contraction activation pattern in bigeminy with electrophysiology study-confirmed site of origin.

Although PVCs commonly lead to degraded cine cardiac MRI (CMR), patients with PVCs may have relatively sharp cine images of both normal and ectopic beats ("double beats") when the rhythm during CMR is ventricular bigeminy, and only one beat of the pair is detected for gating. MRI methods for directly imaging premature ventricular contractions (PVCs) are not yet widely available. Localization of PVC site of origin with images may be helpful in planning ablations. The contraction pattern of the PVCs in bigeminy provides a "natural experiment" for investigating the potential utility of PVC imaging for localization. The purpose of this study was to evaluate the correlation of the visually assessed site of the initial contraction of the ectopic beats with the site of origin found by electroanatomic mapping. Images from 7 of 86 consecutive patients who underwent CMR prior to PVC ablation were found to include clear cine images of bigeminy. The visually apparent site of origin of the ectopic contraction was determined by three experienced, blinded CMR readers and correlated with each other, and with PVC site of origin determined by 3D electroanatomic mapping during catheter ablation. Blinded ascertainment of visually apparent initial contraction pattern for PVC localization was within 2 wall segments of PVC origin by 3D electroanatomic mapping 76% of the time. Our data from patients with PVCs with clear images of the ectopic beats when in bigeminy provide proof-of-concept that CMR ectopic beat contraction patterns analysis may provide a novel method for localizing PVC origin prior to ablation procedures. Direct imaging of PVCs with use of newer cardiac imaging methods, even without the presence of bigeminy, may thus provide valuable data for procedural planning.

Regulation of beta adrenoceptor-mediated myocardial contraction and calcium dynamics by the G protein-coupled estrogen receptor 1

The G protein-coupled estrogen receptor 1 (GPER) produces cardioprotective effects. However, the underlying mechanisms are not well understood. We aimed to investigate the role of GPER in β adrenoceptor-mediated cardiac contraction and myocardial signaling. In anesthetized animals, intrajugular administration of isoproterenol produces a rapid and sustained rise in left ventricular pressure (LVP) and increases ectopic contractions. Administration of the GPER agonist G-1 during the plateau phase of isoproterenol-induced LVP increase rapidly restores LVP to baseline levels and reduces the frequency of ectopic contractions. In freshly isolated cardiomyocytes, isoproterenol potentiates electrically induced peak currents of L-type Ca2+ channels (LTCC) and increases the potential sensitivity of their inactivation. Coadministration of G-1 prevents isoproterenol-induced potentiation of peak LTCC currents and makes channels more sensitive to being inactivated compared to isoproterenol alone. Isoproterenol treatment of cardiomyocytes without electrical stimulation triggers slow-rising Ca2+ signals that are inhibited by the β1AR antagonist metoprolol but not by β2AR antagonist ICI-118551. G-1 pretreatment dose-dependently suppresses isoproterenol-induced total Ca2+ signals and the amplitude and frequency of the intrinsic Ca2+ oscillatory deflections. Pretreatment with the GPER antagonist G-36 produces opposite effects, dose-dependently increasing these signals. ISO promotes robust phosphorylation of Cav1.2 channels at Ser1928. G-1 pretreatment inhibits isoproterenol-stimulated phosphorylation of Cav1.2 at Ser1928, while G-36 pretreatment enhances this signal. Our data indicate that GPER functions as an intrinsic component of β1AR signaling to moderate myocardial Ca2+ dynamics and contraction.

Alterations in ectopic myocardial contraction assessed using real-time MRI

Author(s): Shahid, Mohammed; Solomon, Joseph; Contijoch, Francisco; Avants, Brian; Yushkevich, Paul; Pilla, James J; Han, Yuchi; Witschey, Walter R

User-initialized active contour segmentation and golden-angle real-time cardiovascular magnetic resonance enable accurate assessment of LV function in patients with sinus rhythm and arrhythmias.

BackgroundData obtained during arrhythmia is retained in real-time cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent evidence to show that rt-CMR can accurately assess beat-to-beat variation in left ventricular (LV) function or during an arrhythmia.MethodsMulti-slice, short axis cine and real-time golden-angle radial CMR data was collected in 22 clinical patients (18 in sinus rhythm and 4 patients with arrhythmia). A user-initialized active contour segmentation (ACS) software was validated via comparison to manual segmentation on clinically accepted software. For each image in the 2D acquisitions, slice volume was calculated and global LV volumes were estimated via summation across the LV using multiple slices. Real-time imaging data was reconstructed using different image exposure times and frame rates to evaluate the effect of temporal resolution on measured function in each slice via ACS. Finally, global volumetric function of ectopic and non-ectopic beats was measured using ACS in patients with arrhythmias.ResultsACS provides global LV volume measurements that are not significantly different from manual quantification of retrospectively gated cine images in sinus rhythm patients. With an exposure time of 95.2 ms and a frame rate of > 89 frames per second, golden-angle real-time imaging accurately captures hemodynamic function over a range of patient heart rates. In four patients with frequent ectopic contractions, initial quantification of the impact of ectopic beats on hemodynamic function was demonstrated.ConclusionUser-initialized active contours and golden-angle real-time radial CMR can be used to determine time-varying LV function in patients. These methods will be very useful for the assessment of LV function in patients with frequent arrhythmias.

Inhibition of 2-Aminoethoxydiphenyl Borate-induced Rat Atrial Ectopic Activity by Anti-arrhythmic Drugs

Background/Aims: 2-aminoethoxydiphenyl borate (2-APB) provokes spontaneous mechanical activity in isolated rat left atria. The present study is to characterize 2-APB-induced ectopic activity in rat atria and to investigate the inhibition of 2-APB-induced ectopic activity by anti-arrhythmic drugs. Methods: 2-APB-induced ectopic activity was measured through an isometric force transducer connected to a multichannel acquisition and analysis system. Intracellular [Ca²⁺]_i was measured with fluorescence laser scanning confocal microscopy. Voltage-dependent L- type Ca²⁺ currents were recorded by using patch-clamp technique. Results: 2-APB dose-dependently increased the ectopic activity of left atria at 1, 5, 10, 20, 50 µM. Anti-arrhythmic drugs, quinidine (10µM), lidocaine (10µM), verapamil (5µM), and amiodarone (50µM,100µM) inhibited 2-APB-induced ectopic activity. 2-APB-induced ectopic activity was inhibited by Ca²⁺-free bath, Na⁺/Ca²⁺ exchanger blockers, 3′,4′-dichlorobenzamil hydrochloride (DHC) and Ni²⁺, not by non-selective cation channel blocker Gd³⁺. 2-APB also induced ectopic contractions in ventricular tissue straps and the ectopic contractions were inhibited by quinidine, verapamil and DHC. Lidocaine, verapamil and DHC inhibited 2-APB-induced increase of intracellular Ca²⁺ concentration in cardiomyocytes. Low molecular weight heparin inhibited phenylephrine (PE)-induced but not 2-APB -induced atria ectopic activity, and the pattern of 2-APB-induced ectopic activity was continuous, distinct from the discontinuous activity induced by PE. Conclusion: 2-APB-induced atria ectopic activity was inhibited by classic anti-arrhythmic drugs quinidine, lidocaine, verapamil, amiodarone, and Na⁺/Ca²⁺ exchanger blockers. It can be used for testing agents able to affect any of Na⁺, Ca²⁺ channel, Na⁺/Ca²⁺ exchanger without selectivity.

Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α1‐ and β1‐adrenoceptors

Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic activity in the pulmonary vein. Mechanical activity of strips of pulmonary vein isolated from male Wistar rats was recorded via an isometric tension meter. Twitch contractions of cardiac myocytes were evoked by electrical field stimulation in a tissue bath through which flowed Krebs-Heinseleit solution warmed to 36-37 degrees C and gassed with 95% O(2) 5% CO(2). The superfusion of noradrenaline induced ectopic contractions in 71 of 76 different isolated pulmonary veins. Ectopic contractions in the pulmonary vein were not associated with electrically evoked twitch contractions. The effect of noradrenaline on the pulmonary vein could be replicated by the simultaneous, but not separate, application of the alpha adrenoceptor agonist phenylephrine and the beta adrenoceptor agonist isoprenaline. The use of selective agonists and antagonists for adrenoceptor subtypes showed that ectopic activity in the pulmonary vein arose from the simultaneous stimulation of alpha(1) and beta(1) adrenoceptors. The application of noradrenaline to isolated strips of left atrium did not induce ectopic contractions (n=10). conclusions: These findings suggest an origin for ectopic activity in the pulmonary vein that requires activation of both alpha and beta adrenoceptors. They also open new perspectives towards our understanding of the triggering of AF.

Effect of glialin on cardiac ventricular arrhythmias and myocardial conduction system in dogs

Intravenous glialin in a dose of 7 mg/kg suppressed the number of ectopic contractions caused by double ligature of the left coronary artery by the method of Harris and almost 2-fold prolonged animal life-span in comparison with the control. The maximum antiarrhythmic effect of glialin developed after 180 min and persisted for 5 h. Glialin injected intravenously (10 mg/kg) after myocardial infarction under conditions of programmed electrical stimulation inhibited conduction of evoked impulse in the atria, Purkinje fibers, and ventricular myocardium and did not modify the effective refractory periods of the atria and ventricles.

Padronização da monitorização eletrocardiográfica por 24 horas em cães

O principal objetivo deste estudo foi propor um padrão normal da monitorização eletrocardiográfica dinâmica em cães das raças Doberman, Boxer e Cocker Spaniel (10 animais de cada raça), possibilitando sua utilização como meio de diagnóstico precoce em cães com cardiomiopatia dilatada. O número de complexos QRS foi maior nos cães Cocker Spaniel. Os batimentos ectópicos ventriculares foram mais freqüentes nos da raça Boxer, entretanto as três raças apresentaram menos de 1% de batimentos ectópicos supraventriculares em relação ao total de batimentos. As freqüências cardíacas mínima, média e máxima foram mais altas na raça Cocker Spaniel. Essa raça permaneceu em taquicardia (freqüência igual ou superior a 120bpm) por maior tempo do que as outras duas raças e em bradicardia (freqüência igual ou menor a 50bpm) por menor tempo, além de apresentar menor quantidade e pausas mais curtas. A variação da freqüência cardíaca demonstrou ser um padrão entre esses animais: na raça Cocker Spaniel, o número de contrações ectópicas isoladas supraventriculares e ventriculares foi inferior a 50 por monitorição de 24 horas; na Boxer, foi inferior a 50 por 24 horas; as assistolias ou pausas maiores do que dois segundos foram freqüentes nas raças Boxer e Doberman e ausentes na Cocker Spaniel; comumente as pausas duraram mais do que três segundos; não se observaram alterações do segmento ST nas três raças.

Occlusion and Reperfusion-Induced Arrhythmias in Rats

The role of blood platelets in ischemia- and reperfusion-induced arrhythmias and the efficacy of three calcium blocking drugs (verapamil, diltiazem, and nicardipine) in preventing the arrhythmias were investigated. Using anesthetized rats, we measured platelet count (Pc) continuously in vivo with a Technicon autocounter. Thromboxane B2 (TxB2) and 6-keto-PGF1 alpha levels in blood from coronary sinus were determined by radioimmunoassay (RIA). Myocardial ischemia and arrhythmias were monitored from lead I ECG during and after occlusion of the left anterior descending coronary artery (LAD) for 7 min. Ischemia-induced arrhythmias were mainly ventricular ectopic contractions (VECs), whereas reperfusion produced VECs, ventricular tachycardia (VT), and reversible and irreversible ventricular fibrillation (VF). Both ischemia and reperfusion decreased platelet count and increased TxB2 level in blood from the coronary sinus. The effects of the CEBs were determined at two dose levels (0.1 and 0.3 mg/kg). Each calcium entry blocker (CEB), at both dose levels, significantly inhibited ischemia-induced arrhythmias. Verapamil and diltiazem significantly reduced reperfusion-induced VECs, prevented VT and irreversible VF, and reduced the number of animals with reversible VF. Nicardipine in preventing arrhythmias was not very effective at either dose. The CEBs also inhibited both ischemia- and reperfusion-induced decreases in PC with a moderate increase (up to 7%) as compared with levels in sham-operated controls. The CEBs also significantly reduced TxB2 levels in blood from the coronary sinus. These results indicate that ischemia and postischemic reperfusion both induce platelet aggregation in rats. Aggregating platelets release biologically active substances including thromboxane A2 (TxA2) which exacerbates existing ischemia and facilitates generation of arrhythmias. CEBs inhibit platelet aggregation and TxA2 release and enhance PGI2 synthesis, thereby preventing arrhythmias.

Mechanical restitution in isolated mammalian myocardium: Species differences and underlying mechanisms

Ventricular myocardium was obtained from guinea-pig, ferret and human hearts. In each case small strips were mounted isometrically in a tissue bath and superfused with a physiological saline at 37°C. The preparations were stimulated at 1 Hz and ectopic stimuli of different preceding intervals were given. The relationship between the force produced by the ectopic contraction and the duration of the preceding interval was plotted to form mechanical restitution curves (MRC). In the guinea-pig the MRC is described by a rapid recovery phase with an exponential time constant of 220 ± 22.7 ms (mean ± s.e.m.) followed by a decay (28.5 ± 8.4 s). In ferret and man the rising phase is described by two exponentials (192.5 ± 43.2 ms and 4.4 ± 1.5 s in the ferret; 259.7 ± 45.2 ms and 3.0 ± 1,0 s in man). The decay phase is slower in ferret (22 ± 156 s, P < 0.02) and man (177 ± 70 s, P < 0.002) than in guinea-pig. There was no significant difference between the time constants of the rapid recovery phase of mechanical restitution in each species. The time constant of the rapid recovery phase ( τ 1) was abbreviated by ryanodine, ouabain and adrenaline in human myocardium and by ryanodine alone in guinea-pig. Verapamil increased τ 1 in both species. The decay time constant ( τ 3) was prolonged by ouabain, verapamil and by increasing extracellular [Ca 2+] in human myocardium and by ouabain and verapamil in guinea-pig. The recovery of the second inward current in human myocardium was not correlated to the recovery of mechanical function. It is suggested that τ 1 is dependent on the recycling of Ca 2+ within the cell as well as the reactivation of the second inward current. The decay phase, τ 3, is dependent on the rate of Ca 2+ efflux from the cell, possibly via a Na +/Ca 2+ exchange mechanism. The mechanisms underlying the slow recovery time constant, τ 2, are unclear but it is important to calculate τ 2 for the proper evaluation of τ 1.

Dynamic changes in left ventricular regional wall thickness during premature ventricular contraction in conscious dogs

The contractile pattern of the regional left ventricular wall during premature ventricular contraction was analyzed in conscious dogs instrumented with an ultrasonic dimension gauge across the anterior and posterior left ventricular walls. Aortic flow was measured with an electromagnetic flow probe. A single premature ventricular contraction was induced by stimulating either the anterior or posterior wall with varied coupling intervals from 380 to 650 msec. Stroke volume of premature ventricular contraction was significantly smaller than that of premature atrial contraction with identical coupling intervals. In premature contractions, stroke volume was linearly related to coupling intervals. Though there was no isovolumic wall thickening in premature atrial contraction, the wall started to thicken during isovolumic ventricular systole in premature ventricular contraction. There was a clear inverse correlation between the ratio of the isovolumic wall thickening to the total wall thickening and coupling intervals. In premature ventricular contractions with identical coupling intervals, the deformation of thickening characteristics was more pronounced in regions with closer proximity to the ectopic focus. Thus it is concluded that the pump function is depressed in premature ventricular contraction, in part due to the increased ratio of wall thickening during isovolumic systole before the opening of the aortic valve. Isovolumic wall thickening increases along with the shorter coupling intervals and closer proximity to the ectopic focus. These alterations in left ventricular mechanical function due to ectopic contraction might induce serious sequelae, depending upon the ectopic focus in the presence of already depressed regional function.

Findings on ambulatory electrocardiographic monitoring in subjects older than 80 years

Twenty-four-hour electrocardiograms were recorded in 50 subjects (44 women, 6 men) older than 80 years without cardiovascular disease and with normal standard electrocardiographic responses. During waking and sleeping periods, the mean sinus rates were, respectively, 78 ± 3 and 64 ± 1 beats/min; heart rate ranged from 43 to 180 beats/min over 24 hours. Supraventricular tachycardia (SVT) was present in 28% of the subjects. Nocturnal sinus arrhythmia was only noted in 12% of the patients; it was accompanied by sinus pauses of 1.8 to 2 seconds, and 1 woman had a transient pattern compatible with atrioventricular dissociation. Supraventricular ectopic contractions (SVECs) were present in all cases. The frequency was less than 1 per hour in 25% and more than 20 per hour in 65%. Serious supraventricular tachyarrhythmias included an episode of ectopic atrial tachycardia (1 subject), a short run of atrial fibrillation (1 subject) and of flutter (1 subject), and several episodes of supraventricular tachycardia (2 subjects), all accompanied by more than 50 SVECs per hour. The number of ventricular premature contractions (VPCs) exceeded 10 per hour in 32% and were multifocal in 18%. There were couplets in 8% and a run of 6 VPCs in 1 subject (2%). In conclusion, sinus pause and atrioventricular block are unusual in people older than 80 years without apparent heart disease. In contrast, frequent SVECs and VPCs are more common. This study stresses the difficulty of evaluating the normality of the electrocardiogram with portable monitoring in the older population.

Submaximal Treadmill Exercise Evaluation in Patients with Symptoms of Cardiovascular Disease: An Aid to Rehabilitation and Re-Employment

The potential benefits of submaximal treadmill exercise testing were evaluated in 250 patients. The exercise endpoint was angina pectoris with a positive test for ischemic heart disease in 27 of 250 (10.8 percent) and paroxysmal atrial tachycardia in two patients. An increase in premature ventricular contractions developed in 32 of 250 patients (12.8 percent) and 18 of 250 patients (7.2 percent) developed more supraventricular ectopic contractions. In 152 patients referred for undiagnosed chest pain, having been considered physically disabled, 100 (65 percent) returned to active work. Of 52 patients with arrhythmias either detected or increased in frequency by testing all but three returned to more activity. It is concluded that submaximal treadmill exercise testing is useful in detecting ischemia and arrhythmias in patients with cardiovascular symptoms and aids in returning many patients to more physical activity. The potential benefits of submaximal treadmill exercise testing were evaluated in 250 patients. The exercise endpoint was angina pectoris with a positive test for ischemic heart disease in 27 of 250 (10.8 percent) and paroxysmal atrial tachycardia in two patients. An increase in premature ventricular contractions developed in 32 of 250 patients (12.8 percent) and 18 of 250 patients (7.2 percent) developed more supraventricular ectopic contractions. In 152 patients referred for undiagnosed chest pain, having been considered physically disabled, 100 (65 percent) returned to active work. Of 52 patients with arrhythmias either detected or increased in frequency by testing all but three returned to more activity. It is concluded that submaximal treadmill exercise testing is useful in detecting ischemia and arrhythmias in patients with cardiovascular symptoms and aids in returning many patients to more physical activity.

Comparative antiarrhythmic effects of intravenously administered lidocaine and procainamide and orally administered quinidine

A double-blind control study compared the ventricular antiarrhythmic efficacy of a single dose each of intravenously administered lidocaine and procainamide and orally administered quinidine. A statistically significant reduction in ventricular ectopic contractions occurred immediately and was present 30 minutes and 1 hour after the onset of injection of procainamide. Lidocaine produced a statistically significant reduction in ventricular extrasystoles immediately and for 30 minutes thereafter. No decrease in the incidence of ectopic contractions was observed with either orally administered quinidine or placebo therapy alone. The duration of ventricular antiarrhythmic action of a single injection of procainamide was significantly greater than that of lidocaine. A statistically but probably not clinically significant reduction in systolic blood pressure was observed with procainamide, quinidine and placebo therapy. No change in either systolic or diastolic blood pressure was observed with lidocaine in the dose employed.

Contraction dependency of the positive inotropic action of cardiac glycosides.

The concept that the positive inotropic effect of cardiac glycosides is dependent on the contractile state of the myocardium was tested. Isolated left atria of rabbits, when driven electrically at 15, 30, 60 and 120/min (at 30, 33, or 37°C), responded to ouabain (I µ/ml) in proportion to the number of contractions and not to the time of exposure or frequency of drive. Contraction-related effects were proportional to concentration of ouabain, acetylstrophanthidin, and digoxin. A contraction-related effect of ouabain was observed in anesthetized dogs with surgical A-V block, ventricular electrical drive and right ventricular contractile force recording. Quiescent rabbit atria exposed to ouabain for 30 min at 30°C and then washed in ouabain-free medium, showed minimal positive inotropic effect when stimulation was resumed. Toxic concentration of ouabain (5 µg/ml) in contact with quiescent atria for 30 min and then washed out, on resumption of stimulation had an immediate positive intropic (but no toxic) effect which diminished progressively, in contrast to the rapid development of toxic effects (ectopic contractions and contracture) in atria exposed to this dose of auabain during repetitive contractions. It is concluded that a major part of the positive intropic effect of cardiac glycosides is contraction dependent.

Role of the cardiac nerves in the production of ectopic contractions. I. Ectopic contractions provoked by ocular and vagal compression: Danielopolu, D., and Proca, G. G.: Arch. de Mal. du Cocur, October, 1925, xviii, 625

Role of the cardiac nerves in the production of ectopic contractions. I. Ectopic contractions provoked by ocular and vagal compression: Danielopolu, D., and Proca, G. G.: Arch. de Mal. du Cocur, October, 1925, xviii, 625

THE DIGITALIZED DOG'S HEART AS AFFECTED BY AMYL NITRITE OR ATROPINE, STUDIED ELECTROCARDIOGRAPHICALLY

THE DIGITALIZED DOG'S HEART AS AFFECTED BY AMYL NITRITE OR ATROPINE, STUDIED ELECTROCARDIOGRAPHICALLY