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Biomedical subjects

M B Waxman

Publications and source records attributed to M B Waxman.

At least 37 records · Page 2Linked to original sources
PubMed1985

[In vitro electrophysiological effects of sodium dantrolene on isolated preparations of Purkinje fibers and ventricular myocardium of sheep].

Dantrolene sodium is a drug used in the treatment of spasticity and malignant hyperthermia. It is known to have a myorelaxant effect related to inhibition of the "release" of calcium by the sarcoplasmic reticulum of striated skeletal muscle. A direct cardiac effect which has only recently been suspected was demonstrated in vitro on isolated preparations of sheep Purkinje fibres and ventricular myocardium. Dantrolene caused a spectacular lengthening of the duration of the action potential of Purkinje fibres. This could be due either to an action on the slow calcium current or to stimulation of an ingoing sodium current sensitive to tetrodotoxin (TTX). This effect on the cardiac action potentials could explain the antiarrhythmic properties of dantrolene sodium during attacks of malignant hyperthermia.

Action Potentials↗
PubMed1984

On-line epicardial mapping of intraoperative ventricular arrhythmias: initial clinical experience.

An on-line automatic mapping system was developed for beat by beat display of epicardial activation during ventricular tachycardia induced at the time of cardiac surgery. A sock array of 110 button electrodes was used to record and display local activation on a video monitor at 8.3 ms intervals. On instant replay in slow motion, epicardial pacing sites were accurately localized to the nearest electrode. Local unipolar electrograms were also recorded, first from the sock array, then from an array of 16 transmural needle electrodes. The epicardial display was verified by retrospective manually derived maps using the recorded epicardial electrograms. In four patients with coronary artery disease and recurrent inducible ventricular tachycardia, earliest epicardial activation was located on slow motion replay within 1 minute. Subendocardial sites of early activation were located within 10 minutes by replay of electrograms from the needle array before ventriculotomy. Transmural and endocardial resection of these sites prevented inducibility of the tachycardia on postoperative electrophysiologic study in three of the four patients. There has been no clinical recurrence of ventricular tachycardia after 3 to 14 months of follow-up despite cessation of antiarrhythmic therapy in three of the patients. This technique has unique advantages over existing mapping methods. It provides beat by beat display of activation sequences so that clinical tachycardias that are short in duration or pleomorphic in configuration now become amenable to mapping. In addition, it markedly shortens total time on cardiopulmonary bypass.

Adult↗
PubMed1983

Self-conversion of drug resistant ventricular tachycardia by rapid atrial pacing.

A 523-year-old man with recurrent ventricular tachycardia two months post myocardial infarction is described. The tachycardia resulted in low output and heart failure at the time of presentation. Following electrocardioversion of ventricular tachycardia, sinus rhythm would last for only a few seconds, and ventricular tachycardia could not be terminated or prevented by drugs, nor by overdrive pacing. Over a 20-hour period, asynchronous right ventricular pacing at 30/min resulted in repeated random interruption of successive paroxysms of ventricular tachycardia, resulting in maintenance of sinus rhythm about 60 to 70% of the time. This produced marked hemodynamic improvement and a decrease in the frequency of paroxysms of tachycardia which, however, continued to recur once every few days. Despite their reduced frequency, these paroxysms continued to be resistant to drugs and had to be terminated by cardioversion. At this point it was discovered that rapid atrial pacing was able to terminate the patient's tachycardia reliably and reproducibly. A permanent right atrial externally activated radio frequency pacemaker device was inserted and over the ensuing eighteen-month period the patient self-terminated over fifty discrete episodes of ventricular tachycardia.

Anti-Arrhythmia Agents↗
PubMed1983

On line (real time) quantitative measurement of premature ventricular beats.

A real time system for graphically displaying premature ventricular beat trends is described. The system consists of analog detector circuits coupled to a Fortran based software program for premature ventricular beat processing. The software program runs four independent channels and has three available analysis modes: a "counting" mode which provides a running total of counts to date; an "averaging" mode which displays average number of events over time, and a "ratio" mode which provides an output reflecting changes in the ratio of premature ventricular beats to all beats. Various scale factors can be applied to accommodate differing background states. The system's strengths lie in its simplicity, accuracy, and simultaneous analog display of both the original ECG signal as well as the derived quantitative data.

Cardiac Complexes, Premature↗
PubMed1983

Interactions between the autonomic nervous system and tachycardias in man.

We have endeavoured to present an integrated and dynamic overview of the interaction between the autonomic nervous system and cardiac arrhythmias. Our purpose was not to be comprehensive, detailed, or all inclusive but to present a clinically relevant summary of some of the areas where autonomic tone may be pertinent. Clearly, most arrhythmias are not the result of a primary autonomic nervous system disorder. However, subtle and overt alterations in autonomic tone, interacting with rate, pressure, cardiac volume, contractility, and the intrinsic myocardial electrophysiologic properties likely exert a critical influence on many cardiac arrhythmias. We wish to emphasize that autonomic effects may be temporarily concealed or overwhelmed during certain states or by the administration of drugs. However, the modulating role of neural tone and neurotransmitters is almost always present, contributing significantly to the outcome of therapy.

Anti-Arrhythmia Agents↗
PubMed1983

Effect of adrenergic stimulation and blockade on ventricular defibrillation in the rat.

Ventricular fibrillation was electrically induced in 60 rats and the effects of adrenergic stimulation ad blockade on the time taken to spontaneous reversion to sinus rhythm were determined. Alpha adrenergic stimulation by norepinephrine and phenylephrine infusion shortened ventricular fibrillation from 3.21 +/- 0.42 (+/- S.E.M.) to 1.48 +/- 0.17 sec (P less than .001) and from 5.13 +/- 0.77 to 2.18 +/- 0.27 sec (P less than .001), respectively. Nonselective beta adrenergic stimulation with isoproterenol prolonged the time to defibrillation from 1.65 +/- 0.20 to 7.01 +/- 0.95 sec (P less than .001), whereas beta-2 adrenergic stimulation with salbutamol produced no change. Alpha adrenergic stimulation antagonized the effect of a concomitant isoproterenol infusion (P less than .05). Alpha adrenergic blockade with phenoxybenzamine prolonged ventricular fibrillation (P less than .001) whereas beta blockade with propranolol or metoprolol shortened the duration of fibrillation. It was concluded that these effects were due to direct stimulation and blockade of cardiac adrenergic receptors. These actions were associated with changes in ventricular refractoriness. Cardiac alpha adrenergic stimulation prolonged the ventricular effective refractory period and promoted spontaneous defibrillation. Beta adrenergic stimulation shortened the ventricular effective refractory period and prolonged the time to defibrillation.

Albuterol↗
PubMed1982

Reflex mechanisms responsible for early spontaneous termination of paroxysmal supraventricular tachycardia.

The incidence and possible mechanism of early spontaneous termination of paroxysmal supraventricular tachycardia was studied in 20 consecutive patients. Episodes of induced tachycardia that terminated spontaneously within the 1st minute after initiation were included. Tachycardias ending spontaneously were associated with a reproducible course of hypotension at the onset followed by blood pressure recovery above control levels and termination. Spontaneous termination of tachycardias occurred within the A-V node 18 to 45 seconds (mean +/- standard error of the mean 27.9 +/- 5.3) after their onset. In the supine position (0 degrees) 9 (45 percent) of 20 patients showed spontaneous termination in 36 (16 percent) of 219 episodes of tachycardia. In the head-dependent position (-20 degrees) only 1 (8 percent) of 13 patients manifested spontaneous termination in 2 (4 percent) of 54 episodes. In the head up position (+60 degrees) only 1 (6 percent) of 18 patients exhibited termination in 2 (2 percent) of 102 episodes. After partial cholinergic blockade with intravenous hyoscine butylbromide, 20 mg, or atropine, 0.6 mg, none of five patients showed spontaneous termination in 25 episodes. After beta adrenergic blockade with 10 mg of propranolol intravenously, none of 16 patients showed spontaneous termination in 87 episodes of tachycardia. We conclude that the initial hypotension during tachycardia evokes a sympathetic response that increases blood pressure and this increase in turn causes a rise in vagal tone that breaks the tachycardia.

Adrenergic beta-Antagonists↗
PubMed1981

Torsade de pointes ventricular tachycardia. A complication of disopyramide shared with quinidine.

Two cases of documented torsade de pointes ventricular tachycardia in association with the use of disopyramide are described. One patient had previously experienced an episode suggestive of quinidine induced ventricular tachycardia while the other developed ventricular tachycardia during quinidine treatment which was later exacerbated and sustained by the administration of disopyramide. Both patients exhibited a prolonged QTc or QUc interval at the time of the arrhythmia. These cases suggest that a propensity of ventricular arrhythmias induced by quinidine may identify individuals who are likely to develop similar arrhythmias disopyramide treatment as well.

Aged↗
PubMed1981

Respiratory and vagal modulation of ventricular tachycardia.

This is a report of a case of stable uninterrupted spontaneous ventricular tachycardia which could be temporarily terminated by a strong increase in vagal tone reflexly induced by phenylephrine, 0.2 mg I.V. Following its abolition with procaine amide, 100 mg I.V., ventricular tachycardia was found to be reinducible by deep inspiration for limited periods of time which varied directly with the magnitude of the inspiratory volume. This effect was enhanced by vagal inhibition (atropine, 0.6 mg I.V.) and attenuated or prevented by vagal stimulation (carotid sinus massage or edrophonium 10 mg I.V.). It was concluded that a deep inspiration can, under some circumstances, induce ventricular tachycardia by a mechanism of vagal withdrawal.

Dose-Response Relationship, Drug↗
PubMed1981

Depression of distal AV conduction following ventricular pacing.

A 61-year-old man presented with symptomatic 2 degree Mobitz II AV block in association with bifascicular block. Ventricular pacing resulted in temporary depression of AV conduction. The extent of pacing-induced AV block varied directly with the duration and rate of ventricular pacing. Intracardiac recordings proved that the site of spontaneous and pacing-induced AV block was distal to the His bundle. Possible mechanisms by which this phenomenon may arise and several implications of practical importance are discussed.

Cardiac Pacing, Artificial↗
PubMed1981

Continuous on-line beat-to-beat analysis of AV conduction time.

A simple analog circuit is described which is capable of measuring on a beat-to-beat basis P-R, R-P, P-P, and R-R intervals during sinus rhythm and paroxysmal supraventricular tachycardia. In addition the circuit will emit a pulse when the consecutively alternating P and R wave sequence is interrupted thereby signalling a trigger problem or a change in rhythm. The operation of the device requires proper P and R wave sensing and provides outputs which are linear over a range of rates which are applicable to the human heart.

Atrioventricular Node↗
PubMed1981

Pacing-induced automaticity in sheep Purkinje fibers.

The induction and decay of pacing-induced automaticity were studied in 15 sheep Purkinje fiber preparations superfused with modified Tyrode's solution containing norepinephrine, 2.5 x 10(-7) M. All preparations were quiescent prior to pacing. Spontaneous automaticity could be induced in each preparation provided a sufficient number of pacing stimuli were applied at a fast enough rate. Once the minimum pacing requirements for induction of automaticity were exceeded, the number, total duration, and fastest rate of the induced beats were proportional to the number and rate of the pacing stimuli up to a maximum which could not be exceeded. Consecutive trains of stimuli were additive in inducing automaticity, provided that the pauses between them were short enough to preclude the time-dependent return of automatic properties to their pre-pacing level. Prolonged sequence of fixed pacing trains resulted in stable degrees of automaticity which depended on the length of the pause between them. These observations permit a semiquantitative description of induced automatic behavior and help establish a model that may be useful in future studies.

Action Potentials↗
PubMed1980

Vagal techniques for termination of paroxysmal supraventricular tachycardia.

Maneuvers that reflexly increase vagal tone were deployed to terminate the tachycardia in 68 consecutive patients with paroxysmal supraventricular tachycardia. The order and success rate of the protocol was as follows: 57 episodes were terminated with carotid sinus pressure alone or after pretreatment with edrophonium, 5 were terminated with the Valsalva maneuvers and 6 were terminated with phenylephrine. Potency testing showed that phenylephrine evoked the greatest increase in vagal tone. All cases demonstrated slowing of tachycardia ranging from 40 to 220 ms +/- standard error of the mean (mean 79.0 +/- 3.8 ms) followed by abrupt termination. Pauses after termination ranged from 900 to 3,300 ms (mean 1,683.8 +/- 66.6) with 54 patients showing pauses of 2,000 ms or less. Termination was highly reproducible showing an overall success of 148 (92 percent) of 160 trials among 22 selected cases. The extent of increased vagal tone needed to terminate paroxysmal supraventricular tachycardia was raised by augmented sympathetic tone (infusion of isoproterenol) and decreased by reduced sympathetic tone (pretreatment with propranolol). Thus, paroxysmal supraventricular tachycardia can be rapidly, safety and consistently terminated by maneuvers that reflexly increase vagal tone.

Adolescent↗
PubMed1980

Unidirectional block in Purkinje fibers.

Three methods of inducing focal conduction disturbances in free-running sheep Purkinje fibers (symmetric and asymmetric focal cooling and asymmetric focal crushing) were explored in 50 preparations. Complete unidirectional block was induced in only a minority of symmetrically cooled preparations whereas the asymmetric lesions generated this conduction disturbance in 80-85% of preparations. The block was more stable when induced by crushing than by asymmetric cooling but was more readily reversible with the latter. The direction of block coincided with the least abrupt gradient in the intensity of the lesion (82-94%), was reversible upon reorientation of the cooling lesion, and was independent of anatomic orientation or pre-existing asymmetries of conduction. The models of unidirectional block described in this paper may be useful in the elucidation of the mechanism of asymmetric conduction disturbances and in studies of the mechanism of action of antiarrhythmic drugs.

Action Potentials↗
PubMed1980

Valsalva termination of ventricular tachycardia.

Nine patients with recurrent ventricular tachycardia (VT) that could be repeatedly terminated by a Valsalva maneuver are described. In two, the tachycardia would cease for only a few seconds and then resume, whereas in seven, the tachycardia could be permanently and reproducibly terminated with a Valsalva maneuver. In all patients the tachycardia ended during the strain phase of the Valsalva maneuver, when blood pressure and radiographic measurement indicated that cardiac dimensions had been reduced dramatically. The speed with which the Valsalva maneuver terminated VT incresed in direct proportion to the strain pressure. Maneuvers such as standing or nitroglycerin, which independently reduce cardiac dimensions, enhanced the potency of the Valsalva maneuvers. Pretreatment with atropine or propranolol in four patients did not alter the response of VT to the Valsalva maneuver. Thus, it appears that a strong Valsalva maneuver can terminate some forms of VT, most likely related to an abrupt reduction in cardiac dimensions.

Adolescent↗
PubMed1980

Effects of respiration and posture on paroxysmal supraventricular tachycardia.

The capacity of deep inspiration and the dependent body position to terminate episodes of tachycardia was studied in 11 patients with recurrent paroxysmal supraventricular tachycardia (PSVT). In eight patients, a deep inspiration and a dependent position repeatedly terminated episodes of PSVT. Reasons for failure were found in the other three patients. A deep inspiration or assumption of a dependent position dramatically raised arterial blood pressure and terminated episodes of PSVT by reflexly increasing vagal drive. The magnitude of the rise in blood pressure was directly proportional to the depth of the inspired volume and to the extent of body dependency. The upright position attenuated the respiratory-induced increase in blood pressure and blocked PSVT termination. Likewise, vagal blockade with atropine did not affect the effects of respiration or dependent position on blood pressure but prevented termination of PSVT.

Adult↗
PubMed1980

The effect of antiarrhythmic drugs on depressed conduction and unidirectional block in sheep Purkinje fibers.

We studied the effect of therapeutic concentrations of lidocaine, procainamide, quinidine, propranolol, and diphenylhydantoin on two models of depressed conduction and unidirectional block produced by asymmetric focal cooling and crushing in sheep Purkinje fibers. All drugs were shown to induce reversible deterioration of conduction. Unidirectional block was converted to bidirectional block with each drug. Improvement of conduction was rare and conversion of unidirectional block to bidirectional conduction never was observed. These experiments suggest that all five drugs may act by a uniform mechanism of action in some reentrant ventricular arrhythmias involving a zone of depressed conduction or unidirectional block within the Purkinje network.

Animals↗