INTRODUCTION: Histological abnormalities are common findings in the left atria (LA) of atrial fibrillation (AF) patients. We aimed to assess LA histological abnormalities in our model of spontaneous atrial tachyarrhythmias in rats. MATERIALS AND METHODS: LA sampling was performed in 12 spontaneously hypertensive rats (SHRs) and eight age-matched Wistar-Kyoto (WKY) rats. Tissue sections were stained with Masson's trichrome and Hematoxylin-Eosin-Safran and examined with a light microscope. A 0 to 3 scoring system was used to quantify the severity of LA structural abnormalities. LA von Willebrand factor (vWF) content was also assessed using immunohistochemical staining. RESULTS: In six of the eight SHRs, LA fibrosis, inflammatory infiltrates, and myocyte necrosis of varying grades of severity were observed. The most frequent feature was endocardial fibrosis, which was observed in six SHRs and in none of the WKY rats. Intra-atrial thrombosis was found in three SHRs and in none of the WKY rats. The intensity of vWF-related fluorescence was higher in the atrial endocardium of SHRs compared to age-matched WKY rats. CONCLUSIONS: Our findings reinforce the role of LA structural abnormalities in atrial arrhythmogenicity. However, two SHRs did not present LA histological abnormalities despite the presence of arrhythmias. This finding suggests that the LA remodeling-atrial tachyarrhythmia relationship could be highly nonlinear and that atrial fibrosis is more likely to be a facilitator of atrial arrhythmogenicity, rather than a prerequisite. We also provide evidence that intra-atrial thrombosis accompanies LA structural remodeling in arrhythmic rats. Increased endocardial platelet adhesion molecule vWF could contribute to this increased thrombogenicity.
INTRODUCTION: Histological abnormalities are common findings in the left atria (LA) of atrial fibrillation (AF) patients. We aimed to assess LA histological abnormalities in our model of spontaneous atrial tachyarrhythmias in rats. MATERIALS AND METHODS: LA sampling was performed in 12 spontaneously hypertensiverats (SHRs) and eight age-matched Wistar-Kyoto (WKY) rats. Tissue sections were stained with Masson's trichrome and Hematoxylin-Eosin-Safran and examined with a light microscope. A 0 to 3 scoring system was used to quantify the severity of LA structural abnormalities. LA von Willebrand factor (vWF) content was also assessed using immunohistochemical staining. RESULTS: In six of the eight SHRs, LA fibrosis, inflammatory infiltrates, and myocyte necrosis of varying grades of severity were observed. The most frequent feature was endocardial fibrosis, which was observed in six SHRs and in none of the WKY rats. Intra-atrial thrombosis was found in three SHRs and in none of the WKY rats. The intensity of vWF-related fluorescence was higher in the atrial endocardium of SHRs compared to age-matched WKY rats. CONCLUSIONS: Our findings reinforce the role of LA structural abnormalities in atrial arrhythmogenicity. However, two SHRs did not present LA histological abnormalities despite the presence of arrhythmias. This finding suggests that the LA remodeling-atrial tachyarrhythmia relationship could be highly nonlinear and that atrial fibrosis is more likely to be a facilitator of atrial arrhythmogenicity, rather than a prerequisite. We also provide evidence that intra-atrial thrombosis accompanies LA structural remodeling in arrhythmicrats. Increased endocardial platelet adhesion molecule vWF could contribute to this increased thrombogenicity.
Authors: Jeffrey J Goldberger; Rishi Arora; David Green; Philip Greenland; Daniel C Lee; Donald M Lloyd-Jones; Michael Markl; Jason Ng; Sanjiv J Shah Journal: Circulation Date: 2015-07-28 Impact factor: 29.690