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

Background—Atrial fibrillation (AF) can be initiated by ectopic beats originating from the atrial or great venous tissues. This study investigated the anatomic characteristics and electrophysiological properties of pulmonary veins (PVs), as well as the possible mechanisms and response to drugs of ectopic foci, and assessed the effects of radiofrequency (RF) ablation on AF initiated by ectopic beats originating from PVs. Methods and Results—Seventy-nine patients with frequent episodes of paroxysmal AF and 10 control patients were included. Distal PVs showed the shortest effective refractory periods (ERPs), and right superior PVs showed a higher incidence of intra-PV conduction block than left superior PVs. Superior and left PVs had longer myocardial sleeves than inferior and right PVs, respectively. These electrophysiological characteristics were similar between AF and control patients. Propranolol, verapamil, and procainamide suppressed ectopic beats that originated from the PVs. Of 116 ectopic foci that ...

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Initiation of Atrial Fibrillation by Ectopic Beats Originating From the Pulmonary Veins Electrophysiological Characteristics, Pharmacological Responses, and Effects of Radiofrequency Ablation

The natural history of atrial fibrillation (AF) is characterized by a gradual worsening with time. The recent finding that AF itself produces changes in atrial function and structure has provided a possible explanation for the progressive nature of this arrhythmia. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to an increase in stability of AF. However, 'domestication of AF' must also depend on a 'second factor' since the persistence of AF continues to increase after electrical remodeling has been completed. Atrial contractile remodeling (loss of contractility) leads to a reduced atrial transport function after cardioversion of AF. An important clinical consequence is that during several days after restoration of sinus rhythm, the risk of atrial thrombus formation is still high. In addition, the reduction of atrial contractility during AF may enhance atrial dilatation which may add to the persistence of AF. Tachycardia-induced structural remodeling takes place in a different time domain (weeks to months). Myolysis probably contributes to the loss of atrial contractile force. Although it might explain the loss of efficacy of pharmacological cardioversion and the development of permanent AF, the role of structural remodeling in the progression of AF is still unclear. Atrial structural remodeling also occurs as a result of heart failure and other underlying cardiovascular diseases. The associated atrial fibrosis might explain intra-atrial conduction disturbances and the susceptibility for AF. Thus, both AF itself and the underlying heart disease are responsible for the development of the arrhythmogenic substrate. New strategies for prevention and termination of AF should be build on our knowledge of the mechanisms and time course of AF-induced atrial remodeling.

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Electrical, contractile and structural remodeling during atrial fibrillation

The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties.

Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model

Atrial fibrillation (AF) is an arrhythmia that can occur as the result of numerous different pathophysiological processes in the atria. Some aspects of the morphological and electrophysiological al...

Rory Childers

Papers

Failure in the rate adaptation of the atrial refractory period: its relationship to vulnerability