Abstract 12083: Form Over Function: The Limited Role of (Myo-)Fibroblast - Atrial Cardiomyocyte Coupling in Human AF
Introduction: Atrial fibrosis forms a substrate for atrial fibrillation (AF). In experiments fibrosis can be arrhythmogenic through to excessive deposition of extracellular matrix or through direct cell-cell coupling.
Hypothesis: We hypothesize that direct coupling between (myo-)fibroblast and cardiac myocyte reduces conduction velocity of the human atrium and that pharmacological ablation of (myo-) fibroblasts in the excised left atrial appendage (LAA) from patients with AF results in a normalization of conduction velocity (CV).
Methods: The LAA, obtained during thoracoscopic surgery for AF, were continuously stimulated at 100bpm in an optical mapping setup. Apparent CV was measured after administration of 0,1μM and 1μM Latrunculin-B (ablating myofibroblasts), 38.2μM Calcimycin (ablating fibroblasts), or in controls. Immunohistochemistry was performed (Vimentin, smooth-muscle actin and CD31) to assess presence and distribution of (myo-)fibroblasts. Collagen was quantified from Picrosirius Red staining.
Results: Twentynine LAA were studied (0.1μM and 1μM Latrunculin-B, Calcimycin n=7 and control n=8). Mean baseline CV was 0.21±0.09mm/ms (range 0.07-0.45). CV remained stabile over time compared to controls (0.1μM Latrunculin-B p=0.24, 1μM Latrunculin-B p=0.67 and Calcimycin p=0.11). Clinical characteristics did not correlate with the CV (type, duration of AF, medication). The percentage of fibrosis present in the LAA correlated with the CV (Figure, r=0.41, p=0.04) and the amount of fibroblasts (ρ=0.48, p=0.01). Concordantly with the outcome of the electrophysiological experiments, myofibroblasts were not detected in the LAA.
Conclusion: Pharmalogical ablation of (myo-)fibroblasts does not change CV in the LAA of patients with AF. This suggests a limited role of direct coupling of (myo-)fibroblasts in human AF. Indirect effects, consisting of the extracellular matrix formation, might be of greater importance in the pathophysiology of AF.
- © 2013 by American Heart Association, Inc.