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

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,,) were recorded by means of microelectrode and patch clamp techniques. RESULTS Three to four months after surgery, A animals in the APS state had a dilated LA (146.2 +/- 35.4 cm(2)/m(2) vs. 91.7 +/- 10.4 cm(2)/m(2) 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 proper-ties 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. (C) 2004 by the American College of Cardiology Foundation.