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Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage

Mitsumasa Fukuchi, MD^*, Jun Watanabe, MD^*, Koji Kumagai, MD^*, Yukio Katori, MD, Shigeo Baba, MD^*, Koji Fukuda, MD^*, Takuya Yagi, MD^*, Atsushi Iguchi, MD, Hitoshi Yokoyama, MD, Masahito Miura, MD^*, Yutaka Kagaya, MD^*, Shigekazu Sato, MD, Koichi Tabayashi, MD and Kunio Shirato, MD^*

^* Department of Cardiovascular Medicine, Tohoku University, Graduate School of Medicine, Sendai, Japan
Department of Otolaryngology, Tohoku University, Graduate School of Medicine, Sendai, Japan
Department of Thoracic and Cardiovascular Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan
Department of Cardiovascular Surgery of Tohoku Kosai Hospital, Sendai, Japan

View larger version (134K): [in a new window]   Figure 1 Typical examples of immunohistochemistry for von Willebrand factor in right and left atrial appendages from patients with noncardiac disease (N; 63 years old, male), mitral valvular stenosis (MS; 53 years old, female), and end-stage heart failure (HF; 80 years old, male), respectively. The latter two cases were accompanied by atrial fibrillation. RAA and LAA indicate right and left atrial appendages, respectively. Bar = 200 µm.

View larger version (88K): [in a new window]   Figure 2 (A) Typical examples of immunohistochemistry for endothelial cell markers including von Willebrand factor, CD31 and eNOS in atrial appendages from noncardiac (N) and cardiac patients (HD), between which the immunoreactivity for vWF in the endocardium differed greatly. No specific staining was seen in control sections incubated with nonimmunized immunoglobulin (C). Bar = 100 µm. (B) Electron micrographs of left atrial appendage of a cardiac patient, which had been stained with the immunogold method using polyclonal anti-vWF antibody. Gold particles (arrows) are present in vesicles within the endocardial endothelium and in the subendothelium. EC = endothelial cell; L = lumen. Original magnification x12,000.

View larger version (17K): [in a new window]   Figure 3 Distribution of immunohistochemical grades for von Willebrand factor in the endocardium of atrial appendages according to the underlying cardiac pathogenesis. Immunohistochemical grades for von Willebrand factor were averaged to give a single value to each atrial appendage and were categorized into four ranks (1, 2, 3 and 4). Closed symbols indicate cases of mitral valvular disease in which right and left atrial appendages were paired. There was a significant difference among different groups by Kruskal-Wallis rank test (p < 0.01). Each pairwise comparison was performed by Student-Newman-Keuls test for multiple comparisons. p < 0.01 vs. all groups with underlying cardiac pathogenesis other than IHD (p < 0.05). *p < 0.05; **p < 0.01. ASD = atrial septal defect; AVD = aortic valvular disease; HF = end-stage heart failure; IHD = ischemic heart disease; MVD = mitral valvular disease; N = nondiseased heart; NS = not significant.

View larger version (128K): [in a new window]   Figure 4 Immunohistochemical localization and patterns of platelet adhesion/thrombus formation in atrial appendages of cardiac patients. Immunohistochemistry for glycoprotein Ib/IX and endothelial nitric oxide synthase in serial sections is shown in three typical cases. P = patchy platelet adhesion; T = thrombus; W = widespread platelet adhesion. Bar = 100 µm.

View larger version (20K): [in a new window]   Figure 5 Relation between the immunohistochemical grade for von Willebrand factor (vWF) and the degree of platelet adhesion/thrombus formation in the endocardium. Each symbol indicates a right or left atrial appendage obtained from a cardiac patient. There was a significant correlation between the two variables (r = 0.52, p < 0.01 by Spearman rank correlation) only when the cases who had received warfarin-treatment (closed symbols) were excluded.