Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect–Occlusion Devices

Abstract

Background-We sought to evaluate tissue reactions within and at the surface of devices for interventional therapy of septal defects and to identify antigen characteristics of neotissues. Methods and Results-Atrial or ventricular septal defect-occlusion devices (Amplatzer, nϭ7; Cardioseal/Starflex, nϭ3) were processed using a uniform protocol after surgical removal from humans (implantation time, 5 days to 4 years). Devices were fixed in formalin and embedded in methylmethacrylate. Serial sections were obtained by sectioning with a diamond cutter and grinding, thus saving the metal/tissue interface for histologic evaluation.Immunohistochemical staining was performed using conventional protocols. Superficial endothelial cells stained positive for von Willebrand factor. Within the newly formed tissues, fibroblast-like cells were identified with a time-dependent expression of smooth muscle cell maturation markers (smooth muscle actin, smooth muscle myosin, h-caldesmon, and desmin) beside extracellular matrix components. Neovascularization of the newly formed tissues was demonstrated with the typical immunohistochemical pattern of capillaries and small vessels. Inflammatory cells could be identified as macrophages (CD68ϩ) and both T-type and B-type lymphocytes (CD3ϩ, CD79ϩ). Conclusions-This is the first presentation of results from serial immunohistochemical staining of a collection of explanted human septal-occlusion devices. A time-dependent maturation pattern of the fibroblast-like cells in the neotissues around the implants could be described. Neoendothelialization was seen in all specimens with implantation times of 10 weeks or more. The time course of neoendothelialization, as seen in our study, further supports the clinical practice of anticoagulant or antiplatelet therapy for 6 months after implantation. This time interval should be sufficient to prevent thromboembolic events due to thrombus formation at the foreign surface of cardiovascular implants.

Procoagulant activity induced by transcatheter closure of atrial septal defects is associated with exposure of phosphatidylserine on microparticles, platelets and red blood cells

“…Increased numbers of MPs and PS exposure on platelets and RBCs shortens the coagulation time with a concomitant increase in intrinsic Xase, thrombin, and fibrin production. It has been shown that increased levels of circulating MPs and PS exposure on the cells of their origin enhances PCA in patients with nephrotic syndrome and diabetes mellitus indicate cell activation and/or apoptosis [11,31], clearly supporting our observation. When PS is blocked, PCA is attenuated, Fig.…”

“…Foth [11] report that the Occluder used in this procedure is coated with fibrin and blood cells (mainly RBCs) 5 days after the maneuver, supporting our finding. Fibrin and RBCs might cause further blood cell activation.…”

“…Recent reports show that P-selectin expression on patient's platelets was not elevated significantly, while there was an increase in the formation of prothrombin fragments 1 + 2 (F1 + 2). Fibrin was found on the implant surface on day 5 in case of unsuccessful closure; though no evidence of PCA was seen [11]. Nevertheless, cells and/or other factors that are associated with this hypercoagulable state have not yet been determined.…”

Long-term complications evidenced studying the explanted Gore® HELEX® atrial septal defect occluder seven years after implantation: a case report

“…As was described in the previous reports of the Amplatzer® Atrial Septal Defect Occluder, we found foreign body giant cells located at the tissue-material interface -a convincing evidence of a chronically persisting infl ammatory response [1,4,5,6]. It is supposed that foreign body giant cells can release various tissue remodeling mediators and lead to the degradation of several biomaterials with subsequent device failure [2].…”

“…Following recommendations, published previously [4], the following regions of the specimen were distinguished: the outer cellular layer of the neoendothelium, pseudointimal connective tissue inserted between the neoendothelium and the device, and the neotissue represented by the connective tissue between the disks of the occluder. We found complete endothelialization of the luminal surface of the device, consisting of a single layer of CD34-positive endothelial cells.…”