Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel".

433

159

Catecholamine-induced triggered activity is thought to be caused by intracellular calcium overload mediated by elevation of intracellular cyclic AMP (cAMP). Although shown to occur in isolated preparations, evidence supporting its clinical existence has been lacking. Electrophysiologic studies were performed in four patients with structurally normal hearts who had exertionally related sustained ventricular tachycardia (VT). Programmed stimulation reproducibly initiated and terminated VT in all patients. Induction of tachycardia was also facilitated by infusion of isoproterenol. Adenosine, an endogenous nucleoside, whose only known electrophysiologic effect on ventricular myocardium and Purkinje fibers is antagonism of catecholamine-induced stimulation of intracellular cAMP production, reproducibly terminated all episodes of VT. The tachycardia was also terminated by intravenous verapamil and by the Valsalva maneuver and/or carotid sinus massage. ,(-Adrenergic receptor blockade with propranolol either terminated or prevented induction of VT during programmed stimulation or catecholamine challenge. Adenosine was also administered during VT to 14 patients whose arrhythmias fulfilled standard criteria for reentry, two of whom also had exercise-induced VT. Adenosine, at a dose (112.5 to 225 ,ug/kg iv) sufficient to cause either sinus slowing/arrest or ventriculoatrial block during ventricular pacing, failed to slow or terminate any episode of VT in these patients. Verapamil and autonomic modulation were also ineffective in this group of patients. Adenosine, verapamil, vagal maneuvers (acetylcholine), and ,f-adrenergic receptor blockade are all known to decrease the slow-inward calcium current either directly by modulating calcium channels or indirectly by inhibiting production of cellular cAMP. Therefore the observation in this study that interventions that lower intracellular cAMP either terminate or prevent induction of VT in patients with structurally normal hearts and exercise-induced VT suggests that the mechanism of tachycardia may be cAMPmediated triggered activity. Circulation 74, No. 2, 270-280, 1986. VENTRICULAR TACHYCARDIA (VT) is usually attributed to one of two mechanisms, automaticity or reentry.1"2 A third mechanism of arrhythmia, triggered activity, has been demonstrated in studies of isolated tissues and single cells exposed to cardiac glycosides, high [Ca2l]0 or catecholamines.3-1 This rhythm is initi-

Section: Resultsmentioning

confidence: 99%

Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity.

Lerman¹,

Belardinelli²,

West³

et al. 1986

433

159

“…The stimulator delivered rectangular pulses of variable duration (usually 2-5 msec) at twice diastolic threshold with an accuracy up to l-msec interval. To slow the sinus rhythm, stimulation of the right or left vagosympathetic trunk was accomplished by delivery of 0.5-msec square-wave pulses 1-10 V intensity at a frequency of [10][11][12][13][14][15][16][17][18][19][20] Once a reproducible arrhythmia was established, a nylon sock with 62 individually sewn bipolar electrodes was slipped onto the ventricle for epicardial mapping and positioned with respect to epicardial landmarks. 4 The electrodes were made of Teflon-coated silver wire (0.005 inch in diameter).…”

Section: Methodsmentioning

confidence: 99%

“…'5 Our previous in vitro recordings from the surviving "ischemic" epicardial layer showed cells with variable degrees of partial depolarization (resting potentials from -84 to -50 mV), reduced action potential amplitude and decreased upstroke velocity. 16 Full recovery of responsiveness frequently outlasted the action potential duration reflecting the presence of postrepolarization refractoriness. In these cells, premature stimuli could elicit graded responses over a wide range of coupling intervals.…”

Section: Anatomic Substrate Of Reentrant Circuitsmentioning

confidence: 99%

Reentrant ventricular arrhythmias in the late myocardial infarction period. 9. Electrophysiologic-anatomic correlation of reentrant circuits.

Mehra¹,

Zeiler²,

Gough³

et al. 1983

Self Cite

208

SUMMARY We studied isochronal maps of ventricular activation during ventricular arrhythmias induced by programmed premature stimulation in dogs 3-5 days after ligation of the left anterior descending coronary artery. The entire epicardial surface and selective intramural sites were recorded using a computerized multiplexing technique. The electrophysiologic data were correlated with the anatomic characteristics of the infarction. In nine of 17 dogs (55%), the induced ventricular rhythm was due to reentrant activation in the surviving epicardial layer overlying the infarction. The irregular epicardial layer (up to 4 mm thick) had grossly intact myocardial fibers on microscopic examination but showed abnormal electrophysiologic characteristics. The stimulated premature beat that initiated reentry produced a continuous arc offunctional conduction block within the surviving epicardial layer. The activation wave front circulated slowly around both ends of the arc of block, rejoined on the distal side of the arc before breaking through the arc to reactivate an area proximal to the block. This resulted in splitting of the initial single arc of block into two arcs. Reentrant activation continued as two synchronous circuits that traveled clockwise around one arc and counterwise around the other. Reentry spontaneously terminated when the leading edge of both reentrant circuits encountered refractory tissue, resulting in the coalescence of the two arcs of block into one.The present study may increase the understanding of the electrophysiologic mechanism of some ventricular repetitive responses and tachyarrhythmias induced by programmed premature stimulation in the clinical laboratory.IN OUR recent study on isochronal mapping of induced ventricular arrhythmias in dogs during the late myocardial infarction period,' we showed that a reentrant circuit located on the epicardium is responsible for the induced arrhythmias. The reentrant circuit consisted of a functional arc of conduction block around which the activation wave front advanced in a circular manner at slow and irregular speed. In that study, however, epicardial recordings were obtained from a grid of electrodes placed on the infarction and border zones and complete ventricular activation was not mapped. To determine the overall ventricular activation pattern during induced ventricular arrhythmias in dogs 3-5 days after ligation of the left anterior descending coronary artery, we recorded from electrodes spread over the entire epicardial surface and from selective intramural sites using a computerized multiplexing technique. The electrophysiologic observations were then correlated with the anatomic characteristics of the infarction. after coronary artery occlusion, the dogs were reanesthetized with sodium pentobarbital, 30 mg/kg i.v., and ventilated with a positive-pressure respirator. A left lateral thoracotomy was then performed and the pericardium was used to cradle the heart. Electrocardiographic leads I and II and femoral blood pressure were continuously monitore...

“…Earliest retrograde atrial activation was mapped to the os of the coronary sinus. PJRT was differentiated from the fast-slow form of AV nodal reentry by the ability of ventricular extrastimuli to 24 preexcite the atrium during His bundle refractoriness without altering the retrograde activation sequence, thus indicating the presence of an extranodal pathway ( figure 3, A). The presence of an extranodal pathway was also demonstrated by terminating the tachycardia in its retrograde pathway with a ventricular extrastimulus that failed to capture the atrium that was introduced after anterograde His bundle activation ( figure 3, B) .…”

mentioning

confidence: 99%

Differential electrophysiologic properties of decremental retrograde pathways in long RP' tachycardia.

Lerman¹,

Greenberg²,

Overholt³

et al. 1987

Long RP' supraventricular tachycardias (SVT) often demonstrate both slow and decremental conduction properties in the retrograde pathway of the reentrant circuit. The electrophysiologic properties of these pathways are poorly understood. We studied 10 patients with long RP' SVT (RP'/RR, 0.52 to 0.71); five had the unusual form of atrioventricular nodal reentry (fast-slow) and five patients had accessory AV pathways with slow, decremental retrograde conduction properties. During SVT, the effects of intravenous adenosine (37.5 to 150 ,g/kg), which increases potassium current (QK) in supraventricular tissue and hyperpolarizes membrane potential toward Ek (-90 mV), and the response to slow-inward channel blockade with verapamil (0.10 to 0.20 mg/kg iv) were evaluated. Adenosine and verapamil has similar effects in the presence of fast-slow AV nodal reentry since both agents terminated SVT al tissue) or extranodally (accessory AV connection). The intranodal type or the fast-slow form of AV nodal reentry is thought to utilize the fast AV nodal pathway in the anterograde direction and the slow pathway for its retrograde limb,2" but this has not been shown unequivocally to occur.5'6 The electrophysiologic properties of decremental extranodal AV pathways, including posteroseptal connections associated with the permanent form of junctional reciprocating tachycardia (PJRT)7 8 and laterally located accessory AV pathways,9' 10 are also neither completely understood nor adequately defined. It has been postulated that these extranodal pathways may represent either an accessory AV nodal-like structure' 11,12 or an accessory AV pathway with decremental properties.13 Therapy of these tachycardias could be rationally designed if their underlying electrophysiologic properties were better defined.