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AimsCardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood.Methods and resultsVentricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity.ConclusionRT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.

We describe a novel approach for simultaneously determining regional differences in action potential (AP) morphology and tissue electrophysiological properties in isolated atria. The epicardial surface of rat atrial preparations was placed in contact with a multi-electrode array (9 x 10 silver chloride electrodes, 0.1 mm diameter and 0.1 mm pitch). A glass microelectrode (100 MH) was simultaneously inserted into the endocardial surface to record intracellular AP from either of 2 regions (A, B) during pacing from 2 opposite corners of the tissue. AP duration at 80% of repolarisation and its restitution curve was significantly different only in region A (p < 0.01) when AP was initiated at different stimulation sites. Alternans in AP duration and AP amplitude, and in conduction velocity were observed during 2 separate arrhythmic episodes. This approach of combining microelectrode array and intracellular membrane potential recording may provide new insights into arrhythmogenic mechanisms in animal models of cardiovascular disease. Key words: high-density mapping, atrial action potential membrane recordings, electrophysiology, arrhythmogenic mechanisms, atrial fibrillation. Nous decrivons une nouvelle approche visant a determiner les differences regionales entre les morphologies des potentiels d'action (PA) et les proprietes electrophysiologiques du tissu dans un modele d'oreillettes isolees. Nous avons mis la surface epicardique de preparations d'oreillettes de rat en contact avec un reseau d'electrodes multiples (9 rangees de 10 electrodes en chlorure d'argent de 0,1 mm de diametre a une profondeur de 0,1 mm). Simultanement, nous avons insere une electrode de verre (100 MH) a l'interieur de la surface endocardique pour enregistrer des PA intracellulaires dans l'une ou l'autre de 2 regions (A et B) pendant une stimulation electrique a partir de 2 coins opposes de l'echantillon de tissu. A 80 % de la repolarisation, nous notions que la duree du PA et sa courbe de restitution etaient differentes dans la region A (p < 0,01) uniquement lorsque le PA etait declenche a partir de sites de stimulation differents. Nous avons observe une alternance de la duree du PA et de son amplitude, ainsi que de la vitesse de conduction au cours de 2 periodes d'arythmie distinctes. Cette approche qui consiste a associer un reseau de microelectrodes a l'enregistrement de potentiels membranaires intracellulaires pourrait permettre d'obtenir de nouvelles donnees sur les mecanismes proarythmiques dans des modeles animaux de maladie cardiovasculaire. [Traduit par la Redaction] Mots-cles : cartographie a haute densite, enregistrements de potentiels d'action auriculaires, electrophysiologie, mecanismes proarythmiques, fibrillation auriculaire., Introduction To understand the genesis and maintenance of atrial arrhythmias, detailed evaluation of the structural and electrophysiological characteristics of atrial tissue is necessary. Electrophysiological techniques generally available are electro-anatomical mapping, [...]

Aims: Complex propagation patterns are observed in patients and models with stable atrial fibrillation (AF). The degree of this complexity is associated with AF stability. Experimental work suggests reduced wavefront turning as an important mechanism for widening of the excitable gap. The aim of this study was to investigate how sodium channel inhibition by vernakalant affects turning behaviour and propagation patterns during AF.Methods and Results: Two groups of 8 goats were instrumented with electrodes on the left atrium, and AF was maintained by burst pacing for 3 or 22 weeks. Measurements were performed at baseline and two dosages of vernakalant. Unipolar electrograms were mapped (249 electrodes/array) on the left and right atrium in an open-chest experiment. Local activation times and conduction vectors, flow lines, the number of fibrillation waves, and local re-entries were determined. At baseline, fibrillation patterns contained numerous individual fibrillation waves conducting in random directions. Vernakalant induced conduction slowing and cycle length prolongation and terminated AF in 13/15 goats. Local re-entries were strongly reduced. Local conduction vectors showed increased preferential directions and less beat-to-beat variability. Breakthroughs and waves were significantly reduced in number. Flow line curvature reduced and waves conducted more homogenously in one direction. Overall, complex propagation patterns were strongly reduced. No substantial differences in drug effects between right and left atria or between goats with different AF durations were observed.Conclusions: Destabilization of AF by vernakalant is associated with a lowering of fibrillation frequency and inhibition of complex propagation patterns, wave turning, local re-entries, and breakthroughs. [ABSTRACT FROM AUTHOR]