Dirk Durrer

Flow of "injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms.

We recorded 60 DC-extracellular electrograms simultaneously from epicardial and intra- mural sites of the left ventricle of isolated perfused porcine and canine hearts during the first 15 minutes after occlusion of the left anterior descending coronary artery. During coronary occlusion, maximal current flow across the ischemic border occurred when normal cells had repolarized and ischemic cells had not. At that moment, maximal current sources at the normal side of the ischemic border were in the order of 2 μA/mm3 and maximal current sinks were -5 μA/mm3. During propagation of a broad wavefront in nonischemic myocardium, current sources in the wake of the wavefront were about twice as large. Ventricular premature beats usually followed deep negative T waves in ischemic myocardium, when “injury” currents were maximal. Earliest activity always occurred at the normal side of the ischemic border, and whenever Purkinje activity was recorded it preceded myocardial activity in both single premature beats and the initial beats of ventricular tachycardia (VT) or ventricular fibrillation (VF). For later beats of VT, circus movements with a diameter of 1-2 cm were responsible for continuation of the arrhythmia. Dimension and position of the reentrant circuit changed from beat to beat. In VF, fragmentation of wavefronts occurred, and multiple wavelets followed tortuous paths. Circus movements were seldom completed; when they were, their diameter was 0.5 cm. It is concluded that two mechanisms are responsible for the very early ischemic arrhythmias: one, a μfocalμ mechanism located at the normal side of the ischemic border, possibly induced by injury currents in normal Purkinje fibers and, two, macro- and micro-reentry in ischemic myocardium. Circ Res 47:151-165, 1980

Electrical Stimulation of the Heart in Patients with Ventricular Tachycardia

The initiation and termination of tachycardias were studied in five patients who suffered from recurrent attacks of ventricular tachycardia. In four, coronary artery disease with old myocardial infarction was present. A ventricular tachycardia could be initiated in all patients by a single right ventricular premature beat given during regular driving of the right ventricle. The tachycardia could be terminated by a single right ventricular premature beat, or two right ventricular premature beats given in close succession. In four of our patients an early right ventricular premature beat was followed by the next QRS complex of the tachycardia after an interval shorter than compensatory. Our results favor reentry as the causal mechanism for the tachycardias in our patients. Possible pathways for circus reentry leading to ventricular tachycardia can theoretically be composed of (1) the bundle branches, (2) Purkinje fibers with or without adjacent ventricular myocardium, (3) infarcted or fibrotic ventricular tissue, and (4) combinations of (1), (2), and (3).

The effect of acute coronary artery occlusion on subepicardial transmembrane potentials in the intact porcine heart.

Subepicardial transmembrane potentials were recorded from intact pig hearts to observe the changes induced by acute ischemia. Ischemia shortened action potential duration, and decreased its amplitude, upstroke velocity, and resting potential. The cells were unresponsive after 12 to 15 minutes of coronary artery occlusion, yet near normal action potentials could be restored by flushing the occluded artery with saline as late as 40 minutes after occlusion. The unipolar extracellular electrogram reflected unresponsiveness by a monophasic potential. Local refractory periods initially shortened by up to 100 msec. Later, postrepolarization refractoriness occurred and refractory periods lengthened often in excess of basic cycle length, thus resulting in 2:1 responses. The onset of early ventricular arrhythmias often coincided with a period of alternation and 2: 1 responses, especially when these got out of phase in different regions. Reperfusion frequently led to ventricular fibrillation, and was associated with marked inhomogeneity in cellular responses. Re-entry within ischemic myocardium was the most likely mechanism for arrhythmias.

Mechanism and time course of S-T and T-Q segment changes during acute regional myocardial ischemia in the pig heart determined by extracellular and intracellular recordings.

We recorded transmembrane potentials from subepicardial ventricular cells and local extracellular DC electrograms in isolated perfused pig hearts before and after occlusion of the left anterior descending artery. The first change was a decrease in the resting membrane potential, reflected by T-Q depression in the electrogram. After 3 minutes, action potentials shortened and their amplitude decreased, resulting in S-T elevation until, finally, cells in the center of the ischemic zone became totally unresponsive at resting potentials of about −65 mV. This rendered the extracellular complex monophasic. Determination of extracellular potential distribution at 150-250 epicardial sites after 15-30 minutes of occlusion showed an increase of T-Q depression and S-T elevation toward a central area, with maximum values of −15 and +35 mV, respectively. Comparison of amplitude and configuration of intramural and epicardial potential profiles revealed that the potential distribution was homogeneous throughout ischemic parts of the wall. Extracellular epicardial current originated, therefore, from the epicardial intracellular compartment. Maximal current density during late systole was 1 μA/mm 2, flowing in the border zone towards normal myocardium. After 1 hour of occlusion, there was a marked decrease of extracellular DC potentials which could be attributed to transient recovery of electrical activity in the ischemic zone. After 2 hours, the zone of unresponsiveness was larger than after 15 minutes of occlusion, and the overall amplitude of DC potentials had decreased further, possibly because of healing over.

The Role of Premature Beats in the Initiation and the Termination of Supraventricular Tachycardia in the Wolff-Parkinson-White Syndrome

In four patients with WPW syndrome atrial and ventricular premature beats were induced and the changes in form of the ventricular and atrial complexes were studied. Results indicate that, depending upon the timing of the premature atrial beat and the state of refractoriness of the His and Kent bundles, excitation of the ventricles occurs predominantly through the atrioventricular nodal system, predominantly through the Kent bundle or exclusively through one or both conduction systems. With short delays conduction through the Kent bundle may be blocked and only normal excitation of the ventricles occurs. In one patient with a history of attacks of tachycardia these normal QRS complexes were followed by retrograde activation of the atria by the Kent bundle, and attacks of supraventricular tachycardia of shorter or larger duration occurred. They stopped spontaneously, sometimes by delay or block, either of retrograde Kent conduction or of antegrade A-V nodal conduction, making it possible for the sinus node to capture the ventricles. They also could be terminated by induced atrial premature beats.In two patients tachycardias could be induced by appropriately timed ventricular premature beats during regular driving of the right ventricle. In one of these patients a circus movement, involving the Kent bundle, is probably present. By appropriate stimulation of the atria or ventricles during an attack of supraventricular tachycardia in this patient, one cycle length could be shortened without changing those of the following beats. These results suggest that a circus movement involving the atria, the normal atrioventricular conduction system and the Kent bundle is present. In the other patient, not fulfilling the WPW criteria, ventricular or atrial premature beats did not interfere with the basic rhythm of the tachycardia. Two hypotheses for this tachycardia are given: nodal tachycardia caused by rapid firing of the A-V node or a nodal tachycardia caused by a reciprocal mechanism in the A-V junction. The attacks could be blocked too by appropriately timed atrial and ventricular premature beats. No ventricular type of tachycardia could be demonstrated.

Wolff-Parkinson-White syndrome and atrial fibrillation: Relation between refractory period of accessory pathway and ventricular rate during atrial fibrillation

Abstract To assess the relation between the length of the effective refractory period of the accessory pathway and the ventricular rate during atrial fibrillation, we studied two groups of patients with the Wolff-Parkinson-White syndrome: Group I, 17 patients with electrocardiographlcally documented episodes of atrial fibrillation, and Group II, 9 patients without this arrhythmia. In 17 of these 26 patients the effective refractory period of the accessory pathway could be determined by the single test stimulus method during atrial pacing. After measurement of the refractory period, atrial fibrillation was induced by rapid atrial pacing (400 to 500/min). The duration of the effective refractory period of the accessory pathway was found to correlate with the shortest R-R interval and the mean ventricular rate during documented or induced atrial fibrillation. In nine patients the effective refractory period of the accessory pathway could not be determined because the atrium became refractory while atrioventricular (A-V) conduction was still occurring over this pathway. In these patients the right atrium was regularly paced at rates of up to 280/min. All nine patients had 1:1 A-V conduction over the accessory pathway up to driving rates of 240/min. In five patients conduction still manifested a 1:1 ratio at pacing rates of 280/min. During atrial fibrillation all nine patients had a mean ventricular rate greater than 200/min. Although factors other than the effective refractory period of the accessory pathway affect ventricular rate during atrial fibrillation in patients with the Wolff-Parkinson-White syndrome, the duration of this period is of value in identifying patients at risk of having life-threatening high ventricular rates when atrial fibrillation occurs.

The anatomical substrates of wolff-parkinson-white syndrome. A clinicopathologic correlation in seven patients.

Clinicopathological correlations were made on the hearts from seven patients known to have exhibited electrocardiographic evidence of the Wolff-Parkinson-White syndrome. In each case, clinical and pathological investigations were conducted independently, neither group of investigators having knowledge of the others results. In all seven hearts, the entire atrioventricular junctions were serially sectioned. Accessory atrioventricular connections were predicted in all seven cases following electrocardiographic investigation. Connections were identified histopathologically in four hearts in the predicted site. In another case two connections were identified, one being considered responsible for the pre-excitation. In the sixth case a right lateral connection was anticipated, but only accessory nodo-ventricular fibers were identified following histopathologic studies. In the final case, a posterior septal connection was predicted but the entire septum had fibrosed following previous operation. These findings...

Wolff-Parkinson-White syndrome and atrial fibrillation

Abstract To assess the relation between the length of the effective refractory period of the accessory pathway and the ventricular rate during atrial fibrillation, we studied two groups of patients with the Wolff-Parkinson-White syndrome: Group I, 17 patients with electrocardiographlcally documented episodes of atrial fibrillation, and Group II, 9 patients without this arrhythmia. In 17 of these 26 patients the effective refractory period of the accessory pathway could be determined by the single test stimulus method during atrial pacing. After measurement of the refractory period, atrial fibrillation was induced by rapid atrial pacing (400 to 500/min). The duration of the effective refractory period of the accessory pathway was found to correlate with the shortest R-R interval and the mean ventricular rate during documented or induced atrial fibrillation. In nine patients the effective refractory period of the accessory pathway could not be determined because the atrium became refractory while atrioventricular (A-V) conduction was still occurring over this pathway. In these patients the right atrium was regularly paced at rates of up to 280/min. All nine patients had 1:1 A-V conduction over the accessory pathway up to driving rates of 240/min. In five patients conduction still manifested a 1:1 ratio at pacing rates of 280/min. During atrial fibrillation all nine patients had a mean ventricular rate greater than 200/min. Although factors other than the effective refractory period of the accessory pathway affect ventricular rate during atrial fibrillation in patients with the Wolff-Parkinson-White syndrome, the duration of this period is of value in identifying patients at risk of having life-threatening high ventricular rates when atrial fibrillation occurs.

Computer simulation of arrhythmias in a network of coupled excitable elements.

Arrhythmias were simulated in sheets or cables, consisting of coupled excitable elements, which were characterized by a simple regenerative mechanism. The geometry of the network, the amount of coupling among individual elements, and the properties of the elements relating to excita-bility, automaticity, and duration of the refractory period could be adjusted arbitrarily in an interactive computer program. When a critical amount of coupling was present between automatic and non-automatic cells, sustained repetitive activity could be initiated and stopped by stimulation of the elements. Using this mechanism, it also was possible to evoke reciprocal activity in a one-dimensional cable. In uniform sheets of coupled elements, circus movement of the activation front could be evoked. The presence of an obstacle or dispersion of the refractory periods of the elements was not a prerequisite for the initiation of circus movements. The vortex of circus movements in the homogeneous sheets consisted of elements which were inactivated by depolarizing currents from the circulating wavefront. In sheets of sufficient size, multiple vortices could be present. Circ Res 47: 454-466, 1980

Epicardial and intramural excitation in chronic myocardial infarction

Abstract Epicardial and intramural excitation patterns were studied in 10 dogs with myocardial scars of different size and location, produced by occluding a branch of a coronary artery 4 to 10 weeks prior to the experiments. Even the smallest subendocardial scar present in our series, with the largest diameter of nearly 1 cm. and intramural extension of less than one fourth of the thickness of the left ventricular wall, resulted in the occurrence of abnormal Q waves in unipolar epicardial complexes. Under our experimental conditions a close correspondence existed between anatomic extension of the scar and epicardial area showing Q abnormalities; the latter was often slightly larger. We found no evidence for the existence of a silent zone. In infarction, the cavity complex is “transmitted” through the infarcted area toward the epicardial surface. The main reason for the abnormal Q wave in subendocardial infarction is the loss of voltage. There is no delay in excitation of the Purkinje fibers at the endocardial surface of the scar. An “arborization block” was not present. Living intrainfarction muscle fibers are responsible for the transmission of excitation, but intrainfarction excitatory waves follow circuitous routes. The time differences in local excitation between consecutive terminals may be very large. Mean conduction velocity is reduced (intrainfarction block). Evidence is given that, in some instances, excitation reaches the scar from the endocardial surface and progresses through the infarcted area toward the epicardial surface. In the normal muscle surrounding the myocardial infarction, the conduction velocity of the excitatory wave may be reduced (peri-infarction block). If the scar is devoid of muscle fibers, the excitatory wave reaches the epicardial surface by way of these fibers. A small layer of muscle superjacent to a large scar may generate a large and late R wave. Conduction in a tangential direction has been found. Because intrainfarction and peri-infarction block may be present to a varying degree, the term postinfarction block should be used. The epicardial surface of a scar is activated late, except in the case of very small subendocardial scars. Adjacent areas on the epicardial surface may show large differences in time of arrival of the excitatory wave because of the presence of intramural fibrous strands reaching the epicardial surface and separating these areas.