Biomedical subjects

J Brugada

Publications and source records attributed to J Brugada.

At least 127 records · Page 7Linked to original sources

PubMed1991

Mode of action of a new class IC drug (ORG 7797) against atrial fibrillation in conscious dogs.

In five chronically instrumented conscious dogs, we studied the antifibrillatory action of the experimental class IC drug Org 7797 ((16 alpha,17 beta)-17-methylamino-oestra-1,3,5(10)-triene-3,16-diol- (Z)-2-butenedioate). Under control conditions, paroxysms of atrial fibrillation were induced by burst pacing (50 Hz; inducibility 100%) and persisted on the average for greater than 3 min. Org 7797 (1, 2, and 3 mg/kg/h) significantly reduced both inducibility and duration of atrial fibrillation to 25 and 10%, respectively. To elucidate the electrophysiologic mechanisms of this potent antifibrillatory action, we measured the effects of Org 7797 on conduction velocity, effective refractory period (ERP), and wavelength of the atrial impulse. Org 7797 decreased atrial conduction velocity significantly by 18-25% and lengthened ERP by 18-29% (pacing 2-5 Hz). The maximal pacing frequency (Fmax) was decreased from 8.3 to 6.2 Hz. During Fmax, Org 7797 decreased the conduction velocity by 23% and lengthened ERP by 75%, resulting in a prolongation of the wave-length from 9.8 +/- 2.3 cm (control) to 13.7 +/- 2.6 cm (3 mg/kg/h; p less than 0.01). These results indicate that the antifibrillatory action of Org 7797 is based on diminution of the physiologic rate-dependent shortening of refractoriness, resulting in a prolongation of the wavelength during maximal heart rates (HRs). This electrophysiologic effect of the drug will decrease the number of multiple wavelets during fibrillation, thus increasing the statistical chance of spontaneous termination of the fibrillatory process.

Animals↗

PubMed1991

Sustained monomorphic ventricular tachycardia: a single electrocardiographic expression of different patterns of reentry.

UNLABELLED: Sustained monomorphic ventricular tachycardia (SMVT) can be the electrocardiographic expression of a reentrant impulse in the ventricles. In this study we analyzed the different types of reentry that might lead to SMVT. METHODS: The pattern of activation of 73 episodes of SMVT induced in thin sheets of epicardium in 50 Langendorff perfused rabbit hearts were visualized with high resolution epicardial mapping (248 points). RESULTS: Five different patterns of reentry resulting in SMVT were identified: (1) Single-loop reentry around a fixed obstacle (n = 40); (2) Single-loop reentry around a functional arc of conduction block (n = 17); (3) Double-wave reentry around a fixed obstacle (n = 9); (4) Figure-of-eight reentry around two areas of functional block (n = 5); and (5) Multiple synchronized circuits around multiple areas of functional block (n = 2). CONCLUSION: SMVT is a single electrocardiographic expression of different patterns of reentry. Accurate mapping is mandatory to identify the reentrant pathway and the pathophysiological substrate of the arrhythmia.

Animals↗

PubMed1991

On the mechanisms of ventricular tachycardia acceleration during programmed electrical stimulation.

BACKGROUND: The pathophysiological mechanisms leading to acceleration of ventricular tachycardia (VT) are still unclear. METHODS AND RESULTS: High-resolution epicardial mapping was used to study the mechanisms of VT acceleration by programmed electrical stimulation (PES) in a model of sustained reentrant VT in Langendorff-perfused rabbit hearts (n = 40). Three different mechanisms responsible for acceleration of VT were identified: 1) induction of double-wave reentry (n = 6), defined as the occurrence of two successive activation waves circulating in the same direction in the same circuit; 2) change to a functionally determined circuit (n = 4), defined as reentry of the impulse around a functional line of block without involvement of a fixed obstacle; and 3) change of the reentrant circuit to reentry within a different, faster anatomic pathway (n = 3). Analysis of 81 episodes of sustained monomorphic VT induced by PES in 74 patients with clinically documented sustained VT in the setting of chronic coronary artery disease showed that in 22 episodes VT was suddenly accelerated by PES (mean cycle length, from 345 +/- 73 to 277 +/- 71 msec, p less than 0.01). CONCLUSIONS: With the observations made in the experimental model, the following tentative classification of the mechanisms of VT acceleration of the 22 episodes was made: 1) induction of double-wave reentry in two, 2) change to a functionally determined circuit in four, and 3) change to reentry within a faster anatomic circuit in 16. Simple criteria suggest that these mechanisms may apply in the clinical situation.

Animals↗

PubMed1991

A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex.

BACKGROUND: In the differential diagnosis of a tachycardia with a wide QRS complex (greater than or equal to 0.12 second) diagnostic mistakes are frequent. Therefore, we investigated the reasons for failure of presently available criteria, and we identified new, simpler criteria and incorporated them in a stepwise approach that provides better sensitivity and specificity for making a correct diagnosis. METHODS AND RESULTS: A prospective analysis revealed that current criteria had a poor specificity for the differential diagnosis. The value of four new criteria incorporated in a stepwise approach was prospectively analyzed in a total of 554 tachycardias with a widened QRS complex (384 ventricular and 170 supraventricular). The sensitivity of the four consecutive steps was 0.987, and the specificity was 0.965. CONCLUSIONS: Current criteria for the differential diagnosis between supraventricular tachycardia with aberrant conduction and ventricular tachycardia are frequently absent or suggest the wrong diagnosis. The absence of an RS complex in all precordial leads is easily recognizable and highly specific for the diagnosis of ventricular tachycardia. When an RS complex is present in one or more precordial leads, an RS interval of more than 100 msec is highly specific for ventricular tachycardia. This new stepwise approach may prevent diagnostic mistakes.

Diagnosis, Differential↗

PubMed1991

Reentrant excitation around a fixed obstacle in uniform anisotropic ventricular myocardium.

BACKGROUND: The purpose of this study was to investigate the role of tissue anisotropy and dispersion of refractoriness on initiation of reentrant ventricular tachycardia (VT). METHODS AND RESULTS: A ring of perfused uniform anisotropic ventricular epicardium in Langendorff-perfused rabbit hearts was created by an endocardial freezing technique. High-resolution mapping (248 channels) was used to analyze epicardial activation of the left ventricle. One to three premature beats were induced at a total of 272 points in 17 experiments (16 different points around the ring in each experiment). Reentrant VT could be initiated at 43 of the 272 points tested. The cycle length of VT was stable and ranged from 128 to 198 msec (mean, 161 +/- 19 msec). Correlation between conduction velocity and the angle between the circulating activation wave and epicardial fiber orientation showed that in segments of the ring where conduction was perpendicular to the fiber axis, mean conduction velocity was 25 +/- 5 cm/sec compared with 60 +/- 7 cm/sec when conduction was parallel to the fiber orientation. Analysis of the site of unidirectional conduction block showed that in 41 of 43 cases, block occurred while the impulse was propagating parallel to the fiber orientation. Measurement of the refractory periods at either side of the line of unidirectional block showed that only in 12 of 43 cases did block occur while the impulse was propagating into an area with a longer (more than 10 msec) refractory period. CONCLUSIONS: In uniform anisotropic ventricular myocardium, reentrant VT is initiated because lowering the stimulating efficacy of the depolarization wave by premature beats leads to preferential conduction block parallel to the fiber orientation.

Animals↗

PubMed1991

Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium.

BACKGROUND: The aim of this study was to test the hypothesis that electrical uncoupling and depression of the fast sodium channels have differential effects on propagation of the electrical impulse relative to the fiber orientation. METHODS AND RESULTS: In a model of reentrant ventricular tachycardia (VT) (mean cycle length, 144 +/- 13 msec) around a ring of anisotropic myocardium in 10 Langendorff-perfused rabbit hearts, the effects of extracellular K+ concentration [( K+]o) and heptanol were studied. [K+]o and heptanol each had a dose-dependent effect on VT cycle length. However, high [K+]o slowed the VT mainly by depressing longitudinal conduction, whereas heptanol preferentially depressed transverse conduction. The ratio between longitudinal and transverse conduction velocities progressively decreased with high [K+]o and progressively increased with heptanol. Heptanol terminated VT at a mean concentration of 3.5 +/- 0.5 mM. The cycle length before termination was 446 +/- 120 msec (p less than 0.001). In eight of 10 experiments, termination occurred by failure of conduction during transverse propagation. VT terminated at a mean [K+]o of 11.6 +/- 1.8 mM. The cycle length before termination was 493 +/- 341 msec (p less than 0.01). In seven of 10 cases, termination occurred by failure of conduction during longitudinal propagation. In the remaining five episodes (two with heptanol and three with high [K+]o), termination occurred by collision of the reentrant beat with an antidromic impulse being reflected within the ring. In a separate series of six hearts, tetrodotoxin was administered during VT. Like high [K+]o, tetrodotoxin prolonged the cycle length of the VT by preferentially slowing longitudinal conduction, and VT was terminated by longitudinal block. CONCLUSIONS: During reentrant VT, electrical uncoupling of cells by heptanol or modification of active membrane properties by high [K+]o or tetrodotoxin has a differential depressing effect on propagation of the impulse relative to the fiber orientation.

Alcohols↗

PubMed1991

Regional control of atrial fibrillation by rapid pacing in conscious dogs.

BACKGROUND: In five chronically instrumented conscious dogs, we studied the effects of rapid pacing on sustained electrically induced atrial fibrillation. METHODS AND RESULTS: Twenty-three unipolar atrial electrograms were recorded simultaneously from the bundle of Bachmann and the lateral wall of the right and left atria. During sustained atrial fibrillation, the surface electrocardiogram showed continuous irregularities of the baseline without P or F waves as well as an irregular ventricular rhythm with narrow QRS complexes. The atrial electrograms showed rapid irregular activity with a median cycle length of 85 +/- 8 msec and a range (P5-95) of 33 +/- 18 msec. Overdrive pacing of atrial fibrillation was performed using symmetric biphasic rectangular stimuli (2-msec duration, sixfold that of threshold) applied to a pair of stimulating electrodes at the left atrial appendage. Stimulation was started at pacing intervals of about 10 msec longer than the local median fibrillation interval and subsequently shortened in steps of 1 msec. At a critical pacing interval slightly shorter than the median fibrillation interval, the atrium around the pacing site was suddenly captured by the electrical stimuli. The area of local capture had a diameter of 6.1 +/- 1.6 cm. The time window of capture was 12 +/- 4 msec. CONCLUSIONS: These observations show that during electrically induced atrial fibrillation in chronically instrumented conscious dogs, a short excitable gap is present, permitting regional control of the fibrillatory process by rapid pacing.

Animals↗

PubMed1991

Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias.

BACKGROUND: The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts. METHODS AND RESULTS: A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff-perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide. CONCLUSIONS: Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry.

Animals↗

PubMed1990

Clinical and electrophysiologic characteristics of patients with antidromic circus movement tachycardia in the Wolff-Parkinson-White syndrome.

Antidromic circus movement tachycardia was documented in 36 of 345 consecutive patients with Wolff-Parkinson-White syndrome undergoing detailed electrophysiologic evaluation. Twenty-six patients were men and 10 were women (mean age +/- standard deviation 26 +/- 12 years [range 12 to 45]). Multiple accessory pathways were identified in 12 of these 36 patients (33%). Ten of the patients (67%) with clinically documented antidromic tachycardia had multiple accessory pathways. Dizziness and syncope occurred in 61 and 50% of patients with antidromic circus movement tachycardia. Six patients had clinical documentation of atrial fibrillation, and 4 patients (11%) were resuscitated from ventricular fibrillation. In the 36 patients, 56 distinct antidromic tachycardias were recorded and several different pathways were observed. Orthodromic tachycardia was the most frequently associated arrhythmia (72%). Dual atrioventricular nodal pathways were present in 12 patients (33%); however, atrioventricular nodal tachycardia could be initiated in only 2 of them. Interruption of the accessory pathway was successfully performed in all 20 patients undergoing surgery.

Adolescent↗

PubMed1990

Mechanism of action of sotalol in supraventricular arrhythmias.

Sotalol has a virtually unique antiarrhythmic profile in that it combines the properties of the Class II beta-blocking agents with the Class III properties that prolong repolarization. The Class II action exerts a marked effect on atrioventricular nodal conduction and makes sotalol a suitable drug for the treatment of adrenergic-induced supraventricular tachycardias. Sotalol helps to prevent or slow supraventricular arrhythmias involving the atrioventricular node as part of a reentrant pathway and also helps to control the ventricular rate during supraventricular arrhythmias conducted to the ventricles over the normal atrioventricular pathway. The capacity of conduction of accessory pathways is diminished by sotalol, thereby decreasing the ventricular rate during atrial fibrillation in the Wolff-Parkinson-White syndrome. The effects of sotalol on conduction of the cardiac impulse (Class I effects) have been probably overlooked and those on true refractoriness (Class III effects) overestimated.

Heart Conduction System↗

PubMed1990

[Do beta adrenergic receptor blockaders increase bupivacaine cardiotoxicity?].

Bupivacaine is known to impair the electrophysiology of the heart as well as haemodynamic parameters. Administration of calcium channel blockers prior to bupivacaine enhances its cardiotoxicity. This study assessed the effects of bupivacaine at toxic dose in dogs with previous beta-adrenergic receptor blockade. It included 12 dogs anaesthetized with thiopentone, allocated in a control group (n = 6) receiving a bolus of bupivacaine (4 mg.kg-1) and a study group (n = 6) treated with the sequence propranolol (0.2 mg.kg-1) and bupivacaine (4 mg.kg-1), 15 min later. Infranodal conduction (HV conduction times and QRS durations) was worsened in both groups. Previous propranolol administration had no potentiating effects on these parameters. Conversely the latter was responsible of a greater decrease in heart rate, and increase in atrio-ventricular conduction time (77.9% vs 18.7%, p less than 0.05), as well as a more severe hypotension. Moreover, 3 out of the 6 animals in the study group suffered a cardiac arrest between the 5th and the 10th min. It is concluded that in anaesthetized dogs the cardiac and circulatory effects of a toxic dose of bupivacaine are increased in case of preexisting blockade of beta adrenergic receptors.

Adrenergic beta-Antagonists↗

PubMed1990

Ventricular response during irregular atrial pacing and atrial fibrillation.

In the isolated rabbit heart the ventricular response during irregular atrial pacing and atrial fibrillation was studied. Irregular pacing was performed by an algorithm that generated a population of random stimuli within a chosen range of intervals. During incremental regular pacing atrioventricular (AV) Wenckebach conduction occurred at an atrial cycle length of 164 +/- 24 ms (n = 11). During irregular atrial pacing with a variation of 20, 60, and 100 ms second-degree AV block developed at average cycle lengths of 171, 182, and 198 ms, respectively. In contrast, the pacing interval resulting in stable 2:1 AV block was shortened from 131 ms to 120 and 112 ms during irregular pacing with 20- and 60-ms variation. During pacing with 100-ms variation stable 2:1 AV block no longer occurred. Addition of acetylcholine (0.25-0.75 X 10(-6) M) increased the maximal degree of stable AV block during regular pacing. During irregular pacing, however, stable AV block disappeared. Instead, during second-degree AV block a monophasic inverse relationship (r = -1.5 +/- 1.7) between atrial and ventricular rates appeared as a result of an increased occurrence of concealed conduction in the AV junction. Also during electrically induced atrial fibrillation an inverse relationship was found between the atrial and ventricular rate. We conclude that the ventricular rate during atrial fibrillation is not only determined by the properties of the AV node but also by the rate and irregularity of the fibrillatory process.

Acetylcholine↗

PubMed1990

Double-wave reentry as a mechanism of acceleration of ventricular tachycardia.

By using a Langendorff-perfused ring of anisotropic rabbit epicardium, sustained reentrant ventricular tachycardia with a cycle length of 168 +/- 13 msec (n = 26) was induced by programmed electrical stimulation. Continuous left ventricular epicardial mapping with 256 simultaneously recorded unipolar electrograms demonstrated that the tachycardia was based on circuital movement of the impulse around a fixed obstacle. Because of the anisotropic properties of the myocardium, the circuit consisted of a ring with segments in which the circulating wave propagated slowly (20 +/- 2 cm/sec) or faster (62 +/- 4 cm/sec). This was related to transverse or longitudinal propagation in relation to fiber direction. In six of 26 experiments, sudden acceleration in rate of the tachycardia was observed during programmed electrical stimulation. This acceleration was caused by the occurrence of double-wave reentry (two successive waves traveling in the same direction and using the same circuit). In one of the experiments, induction of double-wave reentry was only possible at basal conditions but not after the administration of a class III antiarrhythmic drug. In a seventh experiment, induction of double-wave reentry became possible after the administration of a class IC antiarrhythmic drug. Because conduction velocity around the ring was depressed during acceleration, the total revolution time of the circuit during double-wave reentry was about 120% of that during single-wave reentry. Ventricular tachycardias in which double-wave reentry could be elicited had longer cycle lengths (197 +/- 11 vs. 156 +/- 8 msec, p less than 0.001) and larger excitable gaps (71 +/- 16 vs. 28 +/- 5 msec, p less than 0.001) than those not showing this phenomenon. Double-wave reentry might have important clinical implications in understanding ventricular tachycardia acceleration during programmed electrical stimulation, proarrhythmic effects of drugs, and pathophysiology of rapid ventricular tachycardias.

Animals↗

PubMed1990

[Anisotropy and reentrant ventricular tachycardia: experimental model in the isolated rabbit heart].

The purpose of this study was to study the role of anisotropic distribution of conduction velocity in the initiation and perpetuation of ventricular tachycardia in an experimental model of sustained reentrant ventricular tachycardia in the Langendorff perfused rabbit heart. The hearts of 30 rabbits were used in the study. The right ventricle, the interventricular septum and the endocardial and intramural layers of the left ventricle were destroyed by freezing. In the surviving epicardial layer an obstacle was created using a cryoprobe. Thus, the final preparation consisted of a perfused ring of epicardium in the left ventricle. In 27 of 30 experiments programmed electrical stimulation induced sustained reentrant excitation around the obstacle. The cycle length of the tachycardia ranged from 128 to 197 ms in different experiments (mean 162 +/- 17 ms). During tachycardia in some segments of the ring the impulse propagated parallel to fiber orientation at a mean conduction velocity of 61 +/- 7 cm/s whereas in other segments of the ring the impulse propagated perpendicular to fiber orientation at a mean conduction velocity of 22 +/- 4 cm/s. An excitable gap was present during all episodes of tachycardia. In conclusion, conduction velocity during reentrant tachycardia depends on the relation between direction of propagation and fiber orientation. This anisotropic distribution of conduction velocity can play an important role in the initiation and perpetuation of ventricular tachycardia.

Animals↗

PubMed1989

In vitro study on mechanisms of bupivacaine-induced depression of myocardial contractility.

Although several mechanisms have been proposed to explain bupivacaine cardiotoxicity, the predominant effect remains to be determined. In this study, we used an isolated rabbit right atrial model that reproduces the effects on inotropic and chronotropic functions induced by 0.5 micrograms/mL bupivacaine; then we tried to counteract these events by electrical stimulation or by addition of CaCl2 or adenosine triphosphate (ATP) to the bathing solution. Contractile force was dramatically depressed by bupivacaine alone (-68%), even when the preparation was paced (-59%). CaCl2 partially counteracted this decrease (-37%). Inotropic function was almost completely restored (-9%) when ATP was added before administration of bupivacaine. Inhibition of energy metabolism seems to be a major explanation for bupivacaine cardiotoxicity.

Adenosine Triphosphate↗

PubMed1988

[Mechanisms of the cardiac toxicity of bupivacaine].

Of all the amide local anaesthetics, bupivacaine is said to be the most cardiotoxic. This toxicity is seen mostly when there is a sudden increase in the plasma concentration of bupivacaine. It involves both, or either, electrical and mechanical structures within the heart. The main site of action on cardiac conduction tissue is the Vmax of phase 0 of the action potential of fast-reacting structures (INa current). Bupivacaine, like lidocaine and the other class I antiarrhythmic drugs, blocks the sodium channels, this block being more slowly reversible. The disturbance of sodium channels throughout the heart leads to a decreased conduction speed throughout the conduction system, thus explaining possible acute conduction disturbances originating below the bundle of His. The ventricular dysrhythmias described are due to a re-entry circuit secondary to a slowing in conduction speed. However, the sinus bradycardias and junctional disturbances seen in toxic accidents are probably due to an inhibition of the slow current of the atrial and atrio-ventricular nodes (Isi current). The experimental observation of an increase in the atrial monophase potential and the corrected QT interval suggests that repolarization currents are also involved (IK current ?). It would therefore seem that modifications in membrane permeabilities are the cause of the seriousness of the clinical picture. Bupivacaine, at toxic levels, has a direct effect on contractility. The negative inotropic effects seem to be due to a fall in the intracytoplasmic calcium concentration on which depends the excitation-contraction couple, as well as disturbed cellular energetic events dependent on the contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1988

[Cardiac toxicity of bupivacaine and diazepam. Experimental study in the anesthetized dog].

The use of diazepam has been suggested for the treatment of convulsions resulting from accidental high plasma levels of local anaesthetics. However, it has been reported that this drug may increase the cardiac effects of bupivacaine in dogs. The present study aimed to assess the effects of diazepam on the electrophysiological signs of a high-dose intravenous bolus of bupivacaine in fourteen dogs, divided into two groups, and anaesthetized with thiopentone and ventilated. All the animals were given a bolus dose of 4 mg.kg-1 bupivacaine. Immediately afterwards, group I (n = 7) received 0.8 ml.kg-1 normal saline solution and group II (n = 7) was given 4 mg.kg-1 diazepam over 1 min. The parameters measured on lead II of the electrocardiogram were: cycle length (R-R interval), QRS length (QRS) and QT interval corrected for heart rate (cQT). Intranodal (AH) and His-Purkinje (HV) conduction times were measured with recording bipolar stimulation electrodes (USCI 6F). Mean aortic pressure (Pao) was measured via a femoral arterial line. In the two groups, the parameters were recorded before and 2, 5, 10 and 15 min after the bupivacaine bolus. Arterial blood samples for measurement of bupivacaine and diazepam serum levels were obtained before and 3, 15 and 30 min after the bupivacaine bolus. There was no significant difference between the two groups in the electrophysiological or haemodynamic parameters at any time. However, the increase in HV and QRS length was a little higher in group I than in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

PubMed1988

Electrophysiological effects of the new cardioactive drug CERM 4205: a comparative study in an animal model and in man.

The cardiac electrophysiological effects of CERM 4205, a new cardioactive agent, were studied by means of intracardiac electrodes in man and in anaesthetized dogs. The results show that CERM 4205 is a cardioactive drug with a main inhibitory effect on slow-response structures (sinus and atrioventricular node) with an associated effect on fast-response structures (atrial, His-Purkinje and ventricular tissues). No qualitative differences were observed between the effects observed in man and dogs. In conclusion, the present study confirms that CERM 4205 is a compound with combined class IV and class I electrophysiological effects in dogs and man. The anaesthetized dog appears to be a satisfactory model for the evaluation of the electrophysiological effects of cardioactive drugs.

Adult↗