Background In this study we tested the hypothesis that atrial fibrillation (AF) causes electrophysiological changes of the atrial myocardium which might explain the progressive nature of the arrhythmia. Methods and Results Twelve goats were chronically instrumented with multiple electrodes sutured to the epicardium of both atria. Two to 3 Weeks after implantation, the animals were connected to a fibrillation pacemaker which artificially maintained AF. Whereas during control episodes of AF were short lasting (6±3 seconds), artificial maintenance of AF resulted in a progressive increase in the duration of AF to become sustained (>24 hours) after 7.1±4.8 days (10 of 11 goats). During the first 24 hours of AF the median fibrillation interval shortened from 145±18 to 108±8 ms and the inducibility of AF by a single premature stimulus increased from 24% to 76%. The atrial effective refractory period (AERP) shortened from 146±19 to 95±20 ms (−35%) (S1S1, 400 ms). At high pacing rates the shortening was less (−12%...

Atrial Fibrillation Begets Atrial Fibrillation A Study in Awake Chronically Instrumented Goats

http://www.area-c54.it/public/standardization%20and%20interpretation%20ecg.pdf

AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology.

Halogen bonding has been known in material science for decades, but until recently, halogen bonds in protein–ligand interactions were largely the result of serendipitous discovery rather than rational design. In this Perspective, we provide insights into the phenomenon of halogen bonding, with special focus on its role in drug discovery. We summarize the theoretical background defining its strength and directionality, provide a systematic analysis of its occurrence and interaction geometries in protein–ligand complexes, and give recent examples where halogen bonding has been successfully harnessed for lead identification and optimization. In light of these data, we discuss the potential and limitations of exploiting halogen bonds for molecular recognition and rational drug design.

Principles and applications of halogen bonding in medicinal chemistry and chemical biology.

http://www.infarkt.ru/d/38025/d/recommendations_for_interpretation_of_the_ecg_4.pdf

AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram

The present article is the fourth in a series of 6 documents focused on providing current guidelines for the standardization and interpretation of the electrocardiogram (ECG). The project was initiated by the Council on Clinical Cardiology of the American Heart Association. The rationale for this project and the process for its implementation were described earlier.1 Abnormalities in the ST segment, T wave, and duration of the QT interval reflect abnormalities in ventricular repolarization. These abnormalities are common and often difficult to interpret. The U wave most likely represents an electricmechanical phenomenon that occurs after repolarization is completed. However, it is frequently included in discussions of repolarization and is discussed in this section. The ST segment corresponds to the plateau phase of the ventricular transmembrane action potential. Under normal conditions, the transmembrane voltage changes slowly during this phase and remains at approximately the same level in all ventricular myocardial cells. As a result, only small voltage gradients are present. This absence of pronounced voltage gradients is similar to that which occurs during electric diastole, ie, from the end of repolarization to the onset of the next depolarization, when ventricular myocardial cells are at their resting transmembrane potential of approximately 85 mV. This corresponds to the TP segment on the ECG. The absence of significant voltage gradients in ventricular myocardial cells during these 2 phases of the cardiac cycle explains why the ST and TP segments are normally nearly flat and at approximately the same level; that is, they are isoelectric. The T wave corresponds to the phase of rapid ventricular repolarization (phase 3) of the ventricular action potential.

AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram. Part III: Intraventricular Conduction Disturbances A Scientific Statement From the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 of 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.

Clinical efficacy of amiodarone as an antiarrhythmic agent

Alterations in the sequence of ventricular activation (left bundle branch block occurring spontaneously or induced by atrial pacing; right ventricular pacing) were studied and shown to induce two opposite changes in the order of ventricular repolarization. One, which causes classic secondary T wave changes, occurs and disappears instantaneously, and is proportional in magnitude to the QRS complex but of opposite direction. The other, which requires a long time to reach its maximal effect and to be dissipated, shows the same direction as the abnormal QRS forces but becomes apparent only when normal activation is restored. The former is a well known consequence of prolongation of the activation time, but the latter appears to be modulated by electrotonic interactions occurring during cardiac activation, in such a way that repolarization is delayed in sites where depolarization begins, and accelerated in sites where depolarization terminates. Our study suggests that electrotonically modulated T wave changes show accumulation and memory, and may persist for days or weeks after the provoking stimulus (the change in the activation sequence) is discontinued. The fact that any shift of the activation sequence may produce "pseudoprimary" T wave changes that may persist long after cessation of the triggering factor has wide clinical implications. Electrotonic modulation of ventricular repolarization is a basic electrophysiologic mechanism that may account for several features of normal and abnormal T waves, and for the possible existence of a heart memory.

Julio O. Lázzari

Papers

Clinical efficacy of amiodarone as an antiarrhythmic agent

Electrotonic modulation of the T wave and cardiac memory

The Mechanism of Intermittent Bundle Branch Block: Relationship to Prolonged Recovery, Hypopolarization and Spontaneous Diastolic Depolarization

Intraventricular trifascicular blocks. Review of the literature and classification.

Intraventricular trifascicular blocks. The syndrome of right bundle branch block with intermittent left anterior and posterior hemiblock.