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Moderate and chronic hemodynamic overload of sheep atria induces reversible cellular electrophysiologic abnormalities and atrial vulnerability

Edith Deroubaix, PhD^*, Thierry Folliguet, MD, Catherine Rücker-Martin, PhD^*, Sylvie Dinanian, MD, Christophe Boixel, PhD, Pierre Validire, MD, Pierre Daniel, DVM, André Capderou, MD, PhD^* and Stéphane N. Hatem, MD, PhD^,*

^* CNRS-UMR-8078, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France
Institut Mutualiste Montsouris, Paris, France
Hôpital Antoine Béclère, Clamart, France
INSERM U-460, Hôpital Bichat and INSERM U-621, Université Pierre et Marie Curie, Paris, France

Manuscript received May 28, 2004; revised manuscript received July 12, 2004, accepted July 29, 2004.

^* Reprint requests and correspondence: Dr. Stéphane N. Hatem, INSERM U-460, Medical Hospital Bichat, 46 rue Henri Huchard, 75018 Paris, France (Email: Stephane.Hatem{at}bichat.inserm.fr).

OBJECTIVES: The aim of this study was to evaluate the myocardial consequences of a chronic volume overload of the left atrium (LA).

BACKGROUND: Atrial dilation is a major risk factor for atrial fibrillation (AF), but the underlying mechanisms are poorly understood.

METHODS: A left-right aorto-pulmonary artery shunt (APS) was created in sheep. The cardiopathy was characterized by echocardiography, electrophysiologic testing, and histologic analysis. Cellular action potential (AP) and calcium current (I_Ca) were recorded by means of microelectrode and patch clamp techniques.

RESULTS: Three to four months after surgery, all animals in the APS state had a dilated LA (146.2 ± 35.4 cm²/m² vs. 91.7 ± 10.4 cm²/m² in the control state; p = 0.0024) but remained in sinus rhythm. Repetitive atrial firing was triggered by a single extra beat in five of six animals in the APS state and in two of six animals in the control state. Moreover, in two animals in the APS state, a single extra beat triggered sustained AF. Myocytes were enlarged and 39.8% showed some degree of myolysis. In animals in the APS state, the AP had no plateau phase or small amplitude and numerous myocytes were unexcitable. The I_Ca density was 45.2% lower in APS animals than in control animals. Beta-adrenergic stimulation normalized I_Ca and restored the plateau phase of the AP. After shunt suppression, the electrophysiologic properties of the atria returned to normal.

CONCLUSIONS: The APS induced moderate, isolated LA dilation, which was sufficient to cause major changes in cellular electrophysiologic properties and to render the atria vulnerable to fibrillation. These effects were reversed by shunt suppression.

Abbreviations and Acronyms   AF = atrial fibrillation   AP = action potential   APS = aorto-pulmonary artery shunt   APSR = aorto-pulmonary artery shunt reversion   CHF = congestive heart failure   ERP = effective refractory period   ICa = L-type calcium current   LA = left atria/atrial   LAA = left atrial area   LV = left ventricle/ventricular   RAF = rapid atrial firing

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