Leonard S. Dreifus

Ventricular Fibrillation A Possible Mechanism of Sudden Death in Patients with Wolff-Parkinson-White Syndrome

A case of Wolff-Parkinson-White syndrome associated with ventricular fibrillation is presented. The control of recurrent ventricular fibrillation with large doses of digitalis and other antiarrhythmic drugs, including propranolol, lidocaine, procainamide, and quinidine, is discussed. As far as we can determine, this is the first human case in which the precise onset of ventricular fibrillation was documented. Possible mechanisms are presented that may produce ventricular fibrillation in patients with Wolff-Parkinson-White syndrome associated with atrial flutter or fibrillation.

Inhomogeneous conduction in the A-V node. A model for re-entry.

Abstract Inhomogeneous conduction in the A-V node as well as concealed and manifest A-V nodal re-excitation were observed in isolated, perfused rabbit hearts during the course of electrophysiologic studies on A-V transmission in 98 experiments. Through the use of two simultaneously impaled glass microelectrodes in the A-V junctional tissues, spread of excitation in this region was studied with reference to the atrial and ventricular electrograms. Re-excitation followed in the wake of prolonged A-V conduction and occurred in an area of the A-V transmission system in which conduction was most severely depressed. In some instances, inhomogeneity of conduction permitted a slow but successful transmission in one region of the specialized conducting system with diminution in another. Thus, the impulse was permitted to travel preferentially through the left side of the A-V node, turn and be transmitted in a retrograde fashion along the right side of the A-V junction, where forward conduction was blocked. These results were obtained in the presence of both sinus and A-V junctional beats, and appeared to be compatible with the concept of re-entry.

Newer concepts in the genesis of cardiac arrhythmias

Abstract Current concepts on the electrophysiological basis of cardiac arrhythmias have been reviewed, by incorporating some of the latest information with the time-honored theories and observations of previous investigators. It is inevitably and hopefully anticipated that confirmation or denial of the various hypotheses will soon result in further identification of these concepts.

Electrophysiologic antagonism and synergism of potassium and antiarrhythmic agents

Abstract Interactions of potassium and antiarrhythmic agents on ventricular myocardial electrophysiology were studied in 25 isolated, perfused rabbit hearts by utilizing an intracellular microelectrode technic. Perfusion of quinidine (0.01 mg./ml.) in a normal concentration of potassium (5.6 mEq./L.) caused a significant decrease in the maximal rate of depolarization (−69.1%), heart rate (−40.4%) and the action potential duration per unit of time (−13.8%). Reduction in the height of action and resting potentials was insignificant. Lowering potassium to 0.8 mEq./L., in the presence of the same concentration of quinidine, significantly increased the maximal rate of depolarization (+82.5%), the height of action potential (+8.5%) and resting potential (+9.9%). The action potential duration per unit of time also showed a significant increase (+15.2%) to control value, although the heart rate was further decreased. Initial perfusion of a low potassium solution caused a significant increase in the height of action potential (+3.3%) and resting potential (+7.0%) as well as a significant decrease in the action potential duration per unit of time (−19.2%). The maximal rate of depolarization and the heart rate showed no significant changes. Addition of quinidine to this low potassium perfusate did not produce any appreciable changes in the maximal rate of depolarization, or in the height of action and resting potentials. The action potential duration per unit of time again returned to its control level. Hence, the electrophysiologic action of quinidine was nullified by a low potassium concentration in both groups of experiments. Quite a similar antagonism was demonstrated between low potassium concentration and other antiarrhythmic agents (antazoline and SU-11636), while high potassium concentration (12 mEq./L.) enhanced the depressive effects of these three drugs. The electrophysiologic mechanism of antiarrhythmic agents was discussed, and the clinical importance of controlling serum potassium concentration during the administration of these agents was suggested.

Control of Recurrent Tachycardia of Wolff-Parkinson-White Syndrome by Surgical Ligature of the A-V Bundle

In a patient with WPW, type A, pharmacological therapy and radioactive iodine failed to control the disabling, life-threatening arrhythmia. Surgical ligation of the A-V bundle was undertaken in view of the rapidly deteriorating clinical course. Failure to identify A-V block after several sutures were placed in the A-V junction and subsequent activation of the ventricles in a heart with known A-V block demonstrates that the accessory A-V bundles may completely activate the ventricles. Complete elimination of the recurrent tachycardias after A-V ligation suggests that the normal A-V transmission system may be a crucial link in the circus pathway of WPW tachycardia.

Sites of Impulse Formation within the Atrioventricular Junction of the Rabbit

Spontaneous A-V nodal rhythm was observed in 23 isolated, perfused rabbit hearts during electrophysiologic studies of A-V transmission. In 19 of the 23, the earliest point of activation was determined by recording transmembrane potentials from numerous A-V junctional fibers. Most commonly (15 hearts), the earliest depolarization was found in a specific area of the A-V node near the point where the fibrous A-V ring extending into the coronary sinus joins a portion of A-V ring between right atrial and ventricular free walls. Various observations suggested that this area was the NH region. In the remaining four hearts, the origin of nodal beats was in the AN region. Diastolic depolarization was often seen in and around the earliest point of activation. The A-V interval in these nodal rhythms ranged from −38.7 to +71.6 msec, in contrast to the A-V interval of 93.3 to 135.7 msec during sinus rhythm. In the presence of NH rhythm, different retrograde intranodal conduction time (across the N region) was the major cause for the wide variation of the A-V interval. Wandering of the pacemaker between the S-A and A-V nodes and examples of exit block of A-V nodal impulses were observed.

Interactions of Quinidine and Potassium on Atrioventricular Transmission

The effects of quinidine and its interactions with potassium (K) on atrio-ventricular (A-V) conduction were studied in isolated, perfused rabbit hearts, utilizing microelectrode techniques. Quinidine gluconate (10 mg/liter) was added to perfusion fluid containing either normal [K+] (4.5 mEq/liter), low [K+] (1.5 mEq/liter), or high [K+] (7.5 mEq/liter). The following observations were made: (A) The marked prolongation of A-V conduction time produced by quinidine was antagonized by low K+ and enhanced by high K+ concentration. (B) Quinidine or high K+ concentration prolonged the A-V interval by slowing intra-atrial and His-Purkinje-ventricular conduction

Comparative mechanisms of antiarrhythmic agents.

Abstract Treatment of arrhythmias is best understood if viewed from 2 major electrophysiologic standpoints: disturbances of impulse formation and disturbances of impulse conduction, or both. Arrhythmias secondary to enhanced automaticity are best controlled by agents depressing diastolic depolarization (quinidine, lidocaine and propranolol). Arrhythmias secondary to depressed conduction can be terminated by (1) enhancing conduction velocity by hyperpolarization (bretylium) or increase in membrane responsiveness (diphenylhydantoin) or (2) by further depressing conduction (quinidine and propranolol). Simple prolongation of the effective refractory period can also interrupt reentry. Direct antifibrillatory effects of high levels of potassium are demonstrated. Specific effects on intraatrial, intranodal and subnodal conduction and ineffectiveness of certain antiarrhythmic agents such as lidocaine in the presence of low levels of potassium are also discussed.

Recurrent Wolff-Parkinson-White tachycardia in an infant: successful treatment by a radio-frequency pacemaker.

Abstract A 5 week old infant was successfully treated with use of a radio-frequency pacemaker to terminate recurrent Wolff-Parkinson-White tachycardia. In this instance temporary electronic pacing and later implantation of a permanent pacemaker was lifesaving. The mechanism for termination of Wolff-Parkinson-White tachycardia by pacemaker stimulation is reviewed. This method may have application in any type of recurrent tachycardia in infants as well as adults.

Cardiac arrhythmias following intracardiac surgery

Abstract 1. 1. Of 211 patients undergoing cardiac surgery, serious postoperative arrhythmias developed in thirty-nine (19 per cent). Atrial fibrillation developed in ten patients, atrial flutter in four and atrial tachycardia in two. Nonparoxysmal nodal tachycardia with incomplete A-V dissociation was seen in nine, with reciprocal rhythm in two and with complete A-V dissociation in two. Ventricular bigeminy occurred in three patients with nodal rhythm, and a persistent ventricular bigeminy in six other patients. 2. 2. Invariably, rapid atrial mechanisms developed in the postoperative period in patients who demonstrated premature atrial systoles in the preoperative period. 3. 3. Electrocardiograms taken immediately prior to surgery frequently suggested important clues to the likelihood of serious postoperative arrhythmias. 4. 4. Open procedures carried out with the aid of hypothermia were more frequently associated with serious arrhythmias. 5. 5. All patients having rapid atrial mechanisms responded to redigitalization. However, if digitalis medication was withheld because of the appearance of nonparoxysmal nodal tachycardia, rapid atrial mechanism frequently resulted. 6. 6. Invariably more serious manifestations of these problems developed in patients exhibiting evidence of digitalis excess or insufficient digitalis therapy. 7. 7. The development of nonparoxysmal nodal tachycardia with incomplete or complete dissociation was usually transient and did not require therapy. Digitalis medication should not be withheld in the presence of this mechanism. 8. 8. The development of persistent ventricular ectopic beating or complete A-V heart block associated with nonparoxysmal nodal tachycardia or ventricular tachycardia was a sinister sign; five patients died with these mechanisms. An internal pacemaker with an electrode directly inserted in the myocardium prior to closure of the chest is indicated in these cases. 9. 9. A fourth cause of nonparoxysmal nodal tachycardia, namely, operative procedures performed close to the conduction system, is described.