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Biomedical subjects

W J Mandel

Publications and source records attributed to W J Mandel.

At least 91 records · Page 5Linked to original sources
PubMed1984

Factors related to the induction of ventricular fibrillation in the normal canine heart by programmed electrical stimulation.

Programmed electrical stimulation was performed in eight normal dogs using a stimulator and endocardial electrode catheters identical to those used in human studies. The right and left ventricular apex were paced at a drive cycle length of 400 ms and, in some cases, 500 ms, with a pacing sequence of single (S1S2), double (S1S2S3) and triple (S1S2S3S4) premature impulses introduced after eight paced complexes. Pacing sequences were performed using combinations of pulse width (1, 2 and 4 ms) and current strengths of 2, 5 and 10 times diastolic threshold, and in three dogs, 15 times diastolic threshold. Twenty-two episodes of ventricular fibrillation were initiated in five dogs in 170 pacing sequences using current strengths up to 10 times diastolic threshold, and six episodes of ventricular fibrillation in the two of three remaining dogs tested at 15 times diastolic threshold. Ventricular fibrillation was reproducible on seven of nine occasions. Ventricular fibrillation was never induced by S1S2 at up to 15 times diastolic threshold; it was induced by S1S2S3 in 3 (1.8%) of 170 sequences, but only at 10 times diastolic threshold. It was induced by S1S2S3S4 in 19 (11.4%) of 167 sequences using 2 to 10 times diastolic threshold, although 20 of 28 episodes only occurred with S1S2S3S4 at 10 or more times diastolic threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Evaluation of amiodarone therapy in the treatment of drug-resistant cardiac arrhythmias: long-term follow-up.

The clinical efficacy of amiodarone in the management of complex cardiac arrhythmias refractory to therapy with two or more conventional or other investigational antiarrhythmic agents was determined by long-term follow-up in patients who had received the drug for at least 3 months. A total of 181 patients, classified into four groups (group 1, supraventricular arrhythmias, n = 42; group 2, frequent ventricular premature complexes, n = 46; group 3, nonsustained ventricular tachycardia, n = 16; and group 4, sustained ventricular tachycardia, n = 77) received a daily maintenance dose of 200 to 800 mg amiodarone for up to 30 months. There was a total of 26 deaths (14%). Ten of these were probably attributable to arrhythmia, although all patients had either good or excellent response to therapy over a mean follow-up of 14.9 months prior to death. The drug had to be permanently discontinued because of side effects in only three patients, and in the majority of patients with side effects, symptoms could be alleviated with adjustment of dosage, thyroid replacement therapy, or temporary cessation of therapy. We conclude that amiodarone is highly effective in high-risk patients with complex refractory cardiac arrhythmias, and that close monitoring and prompt recognition of side effects and appropriate adjustment of dosage or institution of supplemental or replacement therapy (in less than 5% of patients) will allow continuation of amiodarone. The benefit of suppression of symptomatic arrhythmias and the potential of prevention of sudden death clearly outweigh the modest incidence of severe side effects.

Aged↗
PubMed1983

Electrophysiologic effects of bretylium on canine ventricular muscle during acute ischemia and reperfusion.

Electrophysiologic effects of bretylium were assessed on a recently developed animal model for analysis of conduction of premature impulses and excitation threshold. Bretylium was administered intravenously 10 mg/kg over 10 minutes followed by 2 mg/min of infusion immediately after coronary ligation. Conduction of the premature impulse was recorded in the epicardial and endocardial sites both in the base-to-apex and apex-to-base directions, in the normal, in the center, and across the border of ischemic myocardium. Compared to the control group of animals, bretylium did not cause any significant change in the conduction characteristics in the ischemic myocardium; however, it delayed the conduction of premature impulses in the normal myocardium. Thus the disparity in conduction times between the normal and the ischemic myocardium was lessened by bretylium. Further, conduction of impulses from normal tissue across the border of ischemia was also delayed. Bretylium also decreased the excitability threshold in the ischemic myocardium, although the normal myocardial excitation threshold was unaffected. These unique effects of bretylium on conduction and excitability in the normal, in the center, and across the border of ischemic myocardium, when a therapeutic dosage of the drug is used, further validate its antiarrhythmic potential and offer an insight into its mechanism of action in the setting of acute myocardial ischemia.

Animals↗
PubMed1983

Electrophysiologic observations during the spontaneous initiation of ischemia-induced ventricular fibrillation.

Electrophysiologic features of spontaneous, ischemia-induced ventricular fibrillation were studied in 17 dogs using multiple endocardial bipoles positioned in normal and ischemic zones and at the border of ischemic myocardium. All dogs showed ventricular tachyarrhythmias prior to the initiation of ventricular fibrillation. The heart rate prior to the fatal arrhythmia in the ventricular fibrillation dogs was significantly faster than that of nonventricular fibrillation dogs. There was no difference in the coupling intervals of the initial premature complex between episodic and sustained ventricular arrhythmia in most dogs. However, shorter coupling intervals initiated sustained arrhythmia in some dogs. Sites of initiation of arrhythmia were mostly in the ischemic zone. Furthermore, diastolic electrical activity was consistently observed in the ischemic zone during fatal arrhythmia in dogs showing diastolic activity. Cycle length during the fatal arrhythmia prior to ventricular fibrillation gradually shortened, whereas cycle length of episodic ventricular tachycardia remained approximately 200 msec followed by lengthening prior to restoration of sinus rhythm. The disparity of local activation (time differences between the earliest and latest onset of the activation in the five recording sites) increased during the fatal arrhythmia. Examples of progressive intraventricular block (Wenckebach-like) between the border and the center of ischemic myocardium leading to ventricular fibrillation are resynchronization of this disparity leading to the termination of ventricular tachycardia are shown. The recording of continuous electrical activity using bipolar electrodes with an interelectrode distance of 1 mm suggests a smaller reentrant pathway during fatal arrhythmia. Our observations confirm the importance of endocardial recordings within ischemic myocardium, and adds new insight into the events leading to both episodic and sustained ventricular tachycardia.

Animals↗
PubMed1983

Electrophysiologic observations on ventricular tachyarrhythmias following reperfusion.

The threat of reperfusion fibrillation could potentially deter attempts of reperfusion in patients with acute myocardial infarction. Delineation of the mechanisms of this arrhythmia could pave the way to newer interventions designed as prevention or definitive treatment. Therefore the purpose of the present study was to investigate the features of initiation of reperfusion-induced ventricular fibrillation, and further to distinguish between episodic and sustained ventricular arrhythmias following reperfusion. Nine instances of reperfusion ventricular fibrillation and five instances of episodic tachyarrhythmia were analyzed in the study utilizing endocardial bipolar electrograms from normal, ischemic, reperfused, and border of these myocardial segments. In 11 of 14 instances, the site of initiation of the tachyarrhythmias was in the reperfused myocardium; however, maintenance of the arrhythmia defined as diastolic and or continuous electrical activity suggestive of reentry was not seen in the reperfused myocardium in any of these instances. Diastolic electrical activity was observed in 8 of 14 instances, and was seen either in the center or border of ischemic myocardium. Neither heart rate or mean aortic pressure was different between episodic and sustained arrhythmia groups; however, the initial beat of the fatal arrhythmia was significantly more premature than that of episodic arrhythmia. In addition, shorter cycle length, greater variations in the cycle length, and greater disparity in local activation during the tachyarrhythmia were seen in the sustained arrhythmia group compared to the episodic group; cycle length increased and the disparity in local activation improved gradually prior to the termination of the arrhythmia. There was no particular difference in conduction delay immediately prior to reperfusion between control and reperfusion ventricular fibrillation groups. We conclude that different mechanisms exist for the initiation and maintenance of reperfusion-induced arrhythmias. Further, several features seem to distinguish episodic from fatal arrhythmias following reperfusion.

Animals↗
PubMed1983

Comparative study of the effect of slow channel inhibiting agents on ischemia-induced conduction delay as relevant to the genesis of ventricular fibrillation.

Conduction delay has been shown to be an important factor in the genesis of ventricular fibrillation (VF). We evaluated the relationship between conduction delay and (1) initiation of VF and (2) the effects of Ca++ blockers on conduction delay in 41 dogs: eight control (nontreated, non-VF); nine ischemic VF; eight verapamil-treated (0.15 mg/kg bolus followed by 7.5 micrograms/kg/min); eight diltiazem-treated (20 micrograms/kg/min); and eight nifedipine-treated (0.1 mg/kg bolus). Propagation of electrically-induced premature impulses from the midmyocardial bipole of one transmural electrode was recorded at epicardial and endocardial bipoles of other electrodes before and 5, 15, and 30 minutes after coronary ligation. Conduction delay (i.e., conduction times compared to preligation levels) of VF, verapamil, diltiazem, and nifedipine groups were compared to control group in normal and in the center and border of ischemic zones in both base to apex (anterograde) and apex to base (retrograde) directions. Results showed that there was no change in conduction delay in the normal zone between control and VF groups or the treated groups, but both in the center and border of ischemic zone VF was quantitatively related to conduction delay and Ca++ blockers, except that nifedipine significantly reduced conduction delay. We conclude that our model provides a new approach to the assessment of anti-VF intervention. Further, verapamil and diltiazem appear to be useful agents in reducing the risk of ischemia-induced reentrant ventricular tachyarrhythmias.

Animals↗
PubMed1983

The electrophysiologic basis for the use of amiodarone for treatment of cardiac arrhythmias.

The electrophysiologic basis for the use of amiodarone in the treatment of cardiac arrhythmias is outlined, with reference to studies in isolated cardiac tissues, whole animal, and human studies. Amiodarone appears to have the distinctive property of directly prolonging action potential duration (and hence refractory periods) in nearly all cardiac tissues. Independent of its effects on refractory periods, conduction may also be impaired in the His-Purkinje system, possibly due to depression of phase 0 of the action potential. Sinus node and atrial automaticity, as well as that arising from diseased Purkinje fibers, may be depressed. Normal ventricular escape pacemakers appear relatively unaffected, however. A nonspecific anti-adrenergic action may contribute to its observed effects. These electrophysiological effects are more obvious and predictable after several weeks of oral treatment than after intravenous administration, suggesting a time-dependent mechanism of action. The drug appears well suited to the prevention of enhanced automaticity in the ventricle and re-entry throughout the heart, and its frequent clinical success in a broad spectrum of cardiac arrhythmias attests to this. Unwanted side effects include sinus node depression, His-Purkinje conduction delay or block, and ventricular arrhythmias enhanced by QT prolongation. However, the frequency of clinically significant examples of unwanted arrhythmic effects appears to be acceptably low.

Action Potentials↗
PubMed1982

Role of intravenous verapamil in supraventricular tachyarrhythmias after open-heart surgery.

Although the antiarrhythmic effects of verapamil (V) have been studied widely, its role in the treatment of atrial tachyarrhythmias after open-heart surgery (OHS) has not been defined. Accordingly, 22 patients were studied using a double-blind randomized crossover protocol 1 to 6 days after OHS, except for one patient, who was studied 90 days after OHS. Atrial fibrillation was seen in 18 and atrial flutter was observed in four patients. Two doses were used, 0.075 and 0.15 mg/kg (not exceeding 10 mg per dose), depending on the response. A positive response consisted of: conversion to sinus rhythm or heart rate less than 100 beats/minute (bpm). Eleven patients received V as the first drug; the remaining 11 received placebo first. Digoxin had been given to 20 patients (0.5 mg average dose) prior to inclusion in the study. Four patients converted to sinus rhythm within 30 minutes after V and one additional patient did so within 10 seconds of placebo administration. The post treatment heart rate combining both low and high dose response was 85 +/- 18 compared to 128 +/- 23 bpm for placebo (M +/- SD, p less than 0.01). The heart rate remained lower than control 30 minutes after V. Transient hypotension required intravenous fluid in one patient. Thus, V safely and rapidly controls heart rate but is not likely to result in immediate conversion to sinus rhythm in patients after OHS.

Adult↗
PubMed1982

Electrophysiologic effects of chronic amiodarone therapy in patients with ventricular arrhythmias.

Detailed electrophysiologic studies were performed in nine patients with chronic refractory ventricular arrhythmias before and after 7 to 20 weeks (mean 11 weeks) of amiodarone therapy. The amiodarone dose at the time of the repeat study ranged from 400 to 800 mg/day. The drug reduced the sinus rate (p less than 0.001) and prolonged the sinoatrial conduction time (p less than 0.05) with some prolongation of the corrected sinus node recovery time. Intra-atrial conduction was slightly prolonged both in sinus rhythm and during atrial pacing. Anterograde conduction through the AV node was significantly prolonged both in sinus rhythm (p = 0.001) and during atrial pacing (p less than 0.005), and Wenckebach AV block was seen at significantly lower atrial pacing rates after the drug (p less than 0.005). The HV interval was prolonged both in sinus rhythm (p less than 0.05) and during atrial pacing (p = 0.001), and so was the QRS width during atrial pacing (p less than 0.005) and the QT interval in sinus rhythm (p less than 0.005) and during atrial pacing (p less than 0.005). Significant prolongation of the refractory periods in the atrium, AV node, and ventricular muscle were also seen following the drug. We concluded that the significant electrophysiologic effects of this drug throughout the heart during chronic oral use attest to its clinical effectiveness in patients with atrial and ventricular arrhythmias. With due care and despite its effects on the HV interval and QRS width, it can be used in patients with intraventricular conduction defects complicating severe organic heart disease.

Aged↗
PubMed1982

A second zone of compensation during atrial premature stimulation: evidence for decremental conduction in the sinoatrial junction.

125 consecutive patients with premature atrial stimulation were studied. Three demonstrated sinus node return cycles that were fully compensatory following premature atrial stimuli delivered early in diastole. This second zone of compensation was unaccompanied by significant alterations in the post-return cycle lengths or in P-wave morphology of the return cycle. To account for the occurrence of a complete compensatory pause following very early premature atrial depolarizations, we consider the possibility that retrograde conduction of the early atrial premature depolarization (APD) in the sinoatrial junction was delayed for a sufficient length of time to allow the sinus node to depolarize spontaneously on schedule. Collision between the APD and sinus beat would then occur despite the marked prematurity of the APD. Thus, the early APD had encountered the relative refractory period of the sinoatrial junction, suggesting that decremental conduction takes place within the sinoatrial region in man. These findings imply that there is the potential for reentry in the region of the human sinoatrial junction.

Aged↗
PubMed1982

The potentiation of warfarin anticoagulation by amiodarone.

The potentiation of the anticoagulant effect of sodium warfarin by amiodarone is reported in 10 patients. Amiodarone appears to augment the depression of vitamin K-dependent coagulation factors caused by warfarin by an uncertain mechanism, and may lead to serious bleeding. The maintenance dose of warfarin should be halved when amiodarone and warfarin are prescribed together.

Aged↗
PubMed1982

The cellular electrophysiologic mechanism of the dual actions of disopyramide on rabbit sinus node function.

To determine the contribution of disopyramide's suggested opposing direct depressant and indirect acceleratory actions on sinus node function, we studied the effects of disopyramide, 1 x 10(-7) to 1 x 10(-4) M, on isolated rabbit sinus node preparations using standard microelectrode techniques. Transmembrane potentials were recorded simultaneously from the sinus node and adjoining crista terminalis area. Disopyramide, as much as 1 x 10(-5) M, had no effects on the sinus cycle length. At a concentration of 1 x 10(-4) M, sinus cycle length was significantly prolonged due to prolongation of the sinus nodal action potential duration. During cholinergic blockade with atropine, 1 x 10(-6) M, disopyramide, 1 x 10(-7) to 1 x 10(-4) M, significantly prolonged sinus cycle length as a result of a prolongation of the sinus nodal action potential duration and a decrease of the slope of phase 4 depolarization. During cholinergic stimulation with carbamyl choline, 1 x 10(-9) M, disopyramide, 1 x 10(-7) to 1 x 10(-6) M, tended to reverse carbamyl choline-induced prolongation of the sinus cycle length (NS). This acceleratory action of disopyramide was caused by a significant increase of the slope of phase 4 depolarization. Disopyramide, 1 x 10(-7) to 1 x 10(-4) M, had no significant effects on corrected sinus node recovery time or on sinoatrial conduction time under any conditions studied. We conclude that disopyramide has a direct depressant action on normal sinus node cells at the upper therapeutic and toxic levels, which is enhanced during cholinergic blockade, and that disopyramide's acceleratory action appears only at much lower concentrations and only during cholinergic stimulation.

Action Potentials↗