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

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Figure 1 Two-dimensional echocardiographic images of left atrium (LA) (A, B) and the mitral annulus (C, D) in the control (A, C) and aorto-pulmonary artery shunt (APS) (B, D) states. Time-motion echocardiographic images of the left ventricle (LV) in the control (E) and APS (F) states.
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Figure 2 Tissue sections from LA after Masson's trichrome staining in the control (A), aorto-pulmonary artery shunt (APS) (B), and aorto-pulmonary artery shunt reversion (APSR) (C) states. (D) Myocyte diameters in the three groups of animals. Example of cell myolysis (E) and percentage of myolytic myocytes (F) in control and APS states. Bar = 40 µm; animal number = 9 (control state), 7 (APS), 6 (APSR). ***p < 0.0001.
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Figure 3 (A) Effective refractory period (ERP) measured in the right atrium during sinus rhythm (SR) and at various cycle lengths in the control, aorto-pulmonary artery shunt (APS), and aorto-pulmonary artery shunt reversion (APSR) states in six G3 animals. (B) Example of repetitive atrial firing and of (C) a sustained episode of atrial fibrillation triggered by a single extra beat in the APS state. A1 (paced) and A2 (premature) atrial electrograms. RAA1 and RAA2 = right atrial electrograms recorded with the quadripolar electrode.
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Figure 4 (A) Examples of the four types of action potential (AP) in the control state. (B) Distribution of the four types of AP recorded in the control, aorto-pulmonary artery shunt (APS), and aorto-pulmonary artery shunt reversion (APSR) states (numbers of animals: 7, 7, and 3, respectively; p < 0.001). (C) Correlation analysis of percent D-type cells as a function of atrial area index. Solid line = regression line; dashed line = 95% confidence interval.
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Figure 5 Membrane capacitance (A) and current density-voltage relationship (B) of atrial myocytes recorded in the control, aorto-pulmonary artery shunt (APS), and aorto-pulmonary artery shunt reversion (APSR) states. Number in parentheses = number of cells tested. The numbers of animals used for A and B were: controls (8, 7), APS (10, 8), and APSR (4, 3). *p < 0.05; ***p < 0.0001.
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Figure 6 (A) Effectof isoproterenol (ISO) on ICa in control and aorto-pulmonary artery shunt (APS) states: initial (open circles) and steady-state effects of 1 µM isoproterenol (solid circles). (B) Current densities before (open bars) and at steady state effects of isoproterenol (hatched bars, +ISO) in the control (19 cells from 7 animals) and APS (27 cells from 9 animals) states. *p < 0.05; ***p < 0.0001. (C) Effect of isoproterenol (solid circles, 4-min exposure) on A-type action potential (AP) in the control state, on B- and D-type AP in the APS state.
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