Microvascular Thrombosis and Cardiac Allograft Vasculopathy in Rat Heart Transplantation (original) (raw)
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The Journal of Heart and Lung Transplantation, 2011
Cardiac allograft vasculopathy (CAV) is a major limitation to the long-term success of cardiac transplantation. Although there are published descriptions of the lesions, there have been no studies delineating the pathology of CAV in a large series of patients who underwent retransplantation for CAV. We reviewed archival records and microscopic sections of surgically explanted hearts from 64 patients who underwent cardiac retransplantation: 54 adults (18 to 70 years old) and 10 children (3 to 15 years old). Vascular lesions were categorized as showing intimal fibromuscular hyperplasia, atherosclerosis and/or inflammation. The degree of luminal narrowing was estimated from gross descriptions and microscopic sections. In total, 75% of hearts had evidence of acute cellular rejection, mostly mild. Intramyocardial arteries showed primarily intimal fibromuscular hyperplasia and inflammation with no atheromas present. Large and branch epicardial coronary arteries were narrowed in at least one artery of all hearts. Lesions in the epicardial coronary arteries were composed of intimal fibromuscular hyperplasia, atherosclerosis and/or inflammation affecting one or more vascular layers (intima, media and adventitia). Severe CAV with >75% luminal narrowing was seen in the LAD in 17% of hearts, the LCx in 17% and the RCA in 22% of hearts. Two hearts had severe narrowing of the left main coronary artery. Nineteen arteries had luminal thrombi. All hearts had narrowing of smaller epicardial branch coronary arteries that was often severe. Atheromas were present in arteries of adults and children; thus, not all atheromas could be considered pre-existing prior to transplantation. Both arteries and veins showed intimal hyperplasia and inflammation. CAV is a pathologically multifaceted disorder that affects large and small epicardial coronary arteries of adults and children, with different types of lesions: intimal fibromuscular hyperplasia; atherosclerosis; and/or inflammation (vasculitis). Therapies to address this disease must take into account the protean nature of the vascular lesions.
Journal of the American College of Cardiology, 2002
We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute cellular rejection and long-term outcome. Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for cellular rejection, vascular rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of cellular rejection (1.7 +/- 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 +/- 0.28 mm, p < 0.0001) and poor seven-year event-free survival (49%, p = 0.01). The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute cellular rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.
Journal of the American …, 2002
We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute cellular rejection and long-term outcome. BACKGROUND Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. METHODS One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for cellular rejection, vascular rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n ϭ 32), ischemia (n ϭ 24), fibrosis (n ϭ 62) or vascular rejection (n ϭ 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. RESULTS Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p ϭ 0.008) and lowest average episodes of cellular rejection (1.7 Ϯ 1.4, p ϭ 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness ϭ 0.59 Ϯ 0.28 mm, p Ͻ 0.0001) and poor seven-year event-free survival (49%, p ϭ 0.01). CONCLUSIONS The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute cellular rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.
New developments in the diagnosis and management of cardiac allograft vasculopathy
1995
New Developments in the Diagnosis and Management of Cardiac Allograft Vasculopathy The major cause of late death in cardiac transplant recipients is cardiac allograft vasculopathy, also referred to as cardiac transplant atherosclerosis, which occurs in as many as 45% of transplant recipients who survive longer than 1 year. It differs from typical atherosclerosis in that intimal hyperplasia is concentric and diffuse, the internal elastic lamina remains intact, calcification is rare, and the disease tends to develop rapidly. Intravascular ultrasound and coronary angioscopy are more sensitive diagnostic measures of cardiac allograft vasculopathy than is coronary angiography. Although retransplantation at present seems to be the only definitive therapy for cardiac allograft vasculopathy, it has shown only fair results. Recent studies have suggested that calcium entry blockers and angiotensin-converting enzyme inhibitors may play a beneficial role in delaying the progression of cardiac allograft vasculopathy. (Tex Heart Inst J 1995; 22:138-44) A dvances in immunosuppression and improved recipient selection have resulted in an increased survival of cardiac allograft recipients, with 1-year survival rates approaching 85%.1-3 Despite this improvement in patient survival, the most common cause of late death is cardiac allograft vasculopathy, a unique and unusually accelerated form of coronary artery disease. Early experiments with canine cardiac transplantation in the late 1960s by Kosek and colleagueS4s 1st reported this phenomenon, and its occurrence in human cardiac allografts was subsequently verified by Thomson6 and by Bieber's group. Cardiac allograft vasculopathy is angiographically evident in as many as 45% of heart transplant recipients who survive 3 or more years;8 and these patients have a 5fold greater relative risk of developing other cardiac events, such as myocardial infarction, terminal heart failure, and sudden death.8 This report reviews the current concepts in the diagnosis and management of cardiac allograft vasculopathy, with specific consideration of the pathologic characteristics, diagnosis, and treatment of the disease.