Abstract The recognition and acceptance of the entity of antibody-mediated rejection (AMR) of solid organs has been slow to develop. Greatest acceptance and most information relates to cardiac ...transplantation. AMR is thought to represent antibody/complement mediated injury to the microvasculature of the graft that can result in allograft dysfunction, allograft loss, accelerated graft vasculopathy, and increased mortality. The morphologic hallmark is microvascular injury with immunoglobulin and complement deposition in capillaries, accumulation of intravascular macrophages, and in more severe cases, microvascular hemorrhage and thrombosis, with inflammation and edema of the affected organ. Understanding of the pathogenesis of AMR, criteria and methods for diagnosis, and treatment strategies are still in evolution, and will be addressed in this review.
During the last 25 years, antibody-mediated rejection of the cardiac allograft has evolved from a relatively obscure concept to a recognized clinical complication in the management of heart ...transplant patients. Herein we report the consensus findings from a series of meetings held between 2010-2012 to develop a Working Formulation for the pathologic diagnosis, grading, and reporting of cardiac antibody-mediated rejection. The diagnostic criteria for its morphologic and immunopathologic components are enumerated, illustrated, and described in detail. Numerous challenges and unresolved clinical, immunologic, and pathologic questions remain to which a Working Formulation may facilitate answers.
In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 ...by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.
Mitral Valve Pathology Fishbein, Gregory A.; Fishbein, Michael C.
Current cardiology reports,
07/2019, Letnik:
21, Številka:
7
Journal Article
Recenzirano
Purpose of Review
This review describes numerous pathologic entities that cause structural abnormalities of the mitral valve. Different pathologic entities involve different components of the ...so-called mitral apparatus: atrial wall, annulus, leaflets, chordae, papillary muscles, and/or left ventricular free wall. These abnormalities can cause valvular stenosis, regurgitation, or both.
Recent Findings
Currently, in addition to open-chest surgery to replace or repair the damaged mitral valve, there are less invasive percutaneous approaches to address mitral valve dysfunction. These include narrowing the orifice, clipping the leaflets, and inserting bioprostheses percutaneously.
Summary
Understanding the structural abnormalities discussed in this review is essential for choosing the optimal therapeutic intervention for mitral valve disease.
While Huntington's disease (HD) is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to ...better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD.
Abstract Background CorMatrix is a decellularized porcine small intestinal submucosa extracellular matrix that has gained attention as a promising alternative to current materials used in cardiac ...repair. While animal models demonstrate integration of CorMatrix material with host tissue, the histologic characteristics of CorMatrix used in humans are less well-characterized. In this retrospective study, we report our experience with CorMatrix material used in pediatric congenital heart surgery and describe the histology of CorMatrix material and of surrounding native tissue in explanted specimens. Methods Records were reviewed of all pediatric patients implanted with CorMatrix from a single institution (2011–2014). Histologic examinations were performed on CorMatrix and other tissues removed. Explanted samples of CorMatrix and adherent tissues were evaluated for inflammation (acute and chronic), fibrosis, necrosis, degenerative changes, eosinophil response, foreign-body giant cell reaction, neovascularization, and calcification of tissues on a semiquantitative basis (0, none; 1, mild; 2, moderate; 3, marked). Presence of degeneration within CorMatrix and necrosis of surrounding tissue were noted. Results CorMatrix was utilized in 532 pediatric heart reconstruction procedures since 2011. Twelve explanted CorMatrix specimens from 11 pediatric patients including 4 valves (2 mitral and 2 aortic) and 8 outflow/septal/conduit patches were identified and evaluated. Six cases (5 patients) demonstrated clinical evidence of graft failure prior to surgery ( n = 6, 1%). Chronic inflammation was seen in adjacent native tissue in 11/12 cases and consisted predominantly of a mixed population of lymphocytes, macrophages, and plasma cells. Acute inflammation was seen in three cases (3/12). Fibrosis of the surrounding native tissue was seen in all CorMatrix specimens. Eosinophils were present in 6/12 cases. Calcification in surrounding tissue was present in 3/12 cases. Giant cell reaction in adjacent native tissue was seen in 8/12 cases. Neovascularization was seen in surrounding native tissue in 5/12 cases. Degeneration of CorMatrix material was seen in 9/12 cases. Necrosis of surrounding tissue was also identified in 5/12 cases. CorMatrix was not resorbed and no cases demonstrated any remodeling of CorMatrix material by integration of native mesenchymal cells or myocytes. Conclusion CorMatrix may be associated with a marked inflammatory response, including a foreign-body giant cell reaction and fibrosis of the surrounding native tissue. Degenerative changes of CorMatrix material are also seen in a majority of explanted specimens. No histologic differences were seen between patients with clinical evidence of graft failure versus patients requiring graft removal due to other factors. Additionally, no cases showed evidence of tissue integration or recellularization of patch material. Our overall clinical experience with CorMatrix demonstrates a favorable outcome for pediatric patients undergoing cardiac reconstructive surgery. However, there is no histologic evidence that CorMatrix acts as a scaffold for reconstitution of the native cardiovascular structures.
Arteriosclerosis: facts and fancy Fishbein, Michael C; Fishbein, Gregory A
Cardiovascular pathology,
11/2015, Letnik:
24, Številka:
6
Journal Article
Recenzirano
Abstract Arterial vascular diseases comprise the leading cause of death in the industrialized world. Every physician learns about the pathology of these diseases in medical school. All pathologists ...evaluate arterial disease in surgical pathology and/or autopsy specimens. All clinicians encounter patients with clinical manifestations of these diseases. With such a common and clinically-important group of entities one would think there would be a general understanding of the “known” information that exists. That is, physicians and scientists should be able to separate what is fact and what is fancy. This review article is intended to generate thought in this regard.
Vagus nerve stimulation (VNS) therapy has been used for chronic heart failure and is believed to improve imbalance of autonomic control by increasing parasympathetic activity. Although it is known ...that there is neural communication between the VN and the cervical sympathetic trunk, there are few data regarding the quantity and/or distribution of the sympathetic components within the vagus nerve (VN).
To examine the sympathetic components within the human VN and correlate them with the presence of cardiac and neurologic diseases.
We performed immunohistochemistry on 31 human cervical and thoracic VNs (total 104 VNs) from autopsies and reviewed the patients' records. We correlated the quantity of sympathetic nerve fibers within the VNs with cardiovascular and neurologic disease states.
All 104 VNs contain tyrosine hydroxylase (TH)-positive (sympathetic) nerve fibers; the mean TH-positive areas were 5.47% in the right cervical VN, 3.97% in the left cervical VN, 5.11% in the right thoracic VN, and 4.20% in the left thoracic VN. The distribution of TH-positive nerve fibers varied from case to case: central, peripheral, or scattered throughout nerve bundles. No statistically significant differences in nerve morphology were seen between diseases in which VNS is considered effective (depression and chronic heart failure) and other cardiovascular diseases or neurodegenerative disease.
Human VNs contain sympathetic nerve fibers. The sympathetic component within the VN could play a role in physiologic effects reported with VNS. The recognition of sympathetic nerve fibers in the VNs may lead to better understanding of the therapeutic mechanisms of VNS.
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