Survival Of Homografts Research Articles

Long-Term Outcome of Homograft Implants Related to Donor and Tissue Characteristics

Cardiovascular homografts are used for right ventricular outflow tract reconstruction. The procedure has excellent survival rates, but many homografts degenerate and require reintervention. Studies analyzing risk factors for reintervention most often focus on recipient and homograft characteristics, with identification of risk factors such as young recipient age and the use of aortic homografts. This study focuses on less known variables, including donor characteristics and homograft management and its effect on long-term outcome of homograft implantation. A retrospective study was conducted of 304 patients undergoing right ventricular outflow tract reconstruction at University Hospital Lund, Sweden, between 1995 and 2008. Follow-up was up to 22 years. Donor, homograft, and recipient characteristics were analyzed. Statistical analyses included the Kaplan-Meier method with log-rank test and Cox proportional hazard regression. Follow-up was 98% complete. There were 12 deaths, and 115 reinterventions were required. Younger donor age was identified as a risk factor. Homografts from multiorgan donors with no ischemic time produced the longest homograft survival. In non-heart-beating donors, long-term results did not differ between 1 and 24 hours of ischemic time and more than 24 hours of ischemic time. Longer retrieval to cryopreservation times seemed to be better compared with shorter time intervals. Long-term outcome was superior in homografts from middle-aged donors. The best long-term outcome was found when homografts were retrieved from organ donors and middle-aged donors. There is no harm extending the ischemic time in non-heart-beating donors to 48 hours to increase the number of possible donors.

Managing failure: Sir Peter Brian Medawar's transplantation research.

Sir Peter Medawar experimentally demonstrated immunological tolerance through his tissue transplantation experiment in the early and mid-1950s. He made a central contribution to modern biomedicine by showing that genetically distinct cells introduced into a body during its foetal phase could not only be permanently tolerated but also make the host accept any subsequent skin grafts from the original cell donors. However, this discovery had only a limited clinical applicability. None could practise Medawar's method on human foetuses in preparation for their future need for organ or skin transplantation. I analyse this problem by focusing on his management of 'failures' during the tissue transplantation experiments. Through statistical, material, theoretical and rhetorical strategies, he managed unsatisfactory findings of his research, including unexpected skin infection, sudden animal death and irregularities in homograft survival times. I argue that these strategies and their inherent ambiguities constituted the course of Medawar's research, enabling him to delineate the temporal dimensions of tolerance and a clinical relevance, which were mutually contradictory. This paper thus illustrates the multiple roles that failures play in scientific research as well as the conflicting outcomes of investigators' efforts to manage them.

How to choose the best available homograft to reconstruct the right ventricular outflow tract

How to choose the best available homograft to reconstruct the right ventricular outflow tract

Homograft survival after tetralogy of Fallot repair: determinants of accelerated homograft degeneration

Homografts are frequently implanted in patients with tetralogy of Fallot (TOF). However, the lifespan of homografts is shorter than that of graft recipients, thus making surgical re-intervention unavoidable. Therefore, to determine variables that could influence their survival, we retrospectively studied the survival pattern of homografts used to treat TOF. Sixty-eight TOF patients, >14 years of age (mean age: 34 +/- 11; 71% male), were selected from our database of congenital cardiology cases. These patients underwent their first homograft implantation at a median age of 24 years (range: 14-49). The primary endpoint, homograft failure, was defined as homograft replacement or percutaneous balloon dilatation when the echocardiographic gradient reached more than 50 mmHg. Kaplan-Meier analysis revealed that the mean event-free survival time of first homografts was 14.6 years (CI, 12.9-16.2 years). The median increase in the homograft gradient was 1.1 mmHg/year (range: 0.0-22.1) for a median follow-up time of 8.4 years (range: 1.3-17.9). Stepwise regression analysis identified the homograft gradient at 1 month after surgery to be prognostic for homograft degeneration (R(2) = 0.23, beta = 0.26, P = 0.001). Immunological variables, gender, and post-operative inflammatory indicators were unrelated to the degree of homograft gradient increase. Finally, patient age at the time of first homograft implantation and previous palliative surgery was significantly associated with the gradient at 1 month (Spearman's rho = -0.41 and -0.29, respectively; P = 0.004 and 0.048, respectively). Homograft survival in patients with TOF repair is quite good. However, some patients develop accelerated homograft degeneration. We found that the gradient of the homograft 1 month after surgery is most indicative of accelerated homograft degeneration. We hypothesize that mechanical, not immunological, factors play an important role in homograft degeneration.

Blair O. Rogers, M.D., 1923 to 2006

Blair O. Rogers, M.D., 1923 to 2006

Progesterone regulates mouse dendritic cells differentiation and maturation

Progesterone, an important factor in the maintenance of gestation in humans and animals, has been demonstrated to lower immune response during pregnancy [Siiteri PK, Stites DP, Immunologic and endocrine interrelationships in pregnancy, Biol Reprod, (1982); Watnick AS, Russo RA, Survival of skin homografts in uteri of pregnant and progesterone–estrogen treated rats, Proc Soc Exp Biol Med, (1968)], which is one of many hypotheses trying to explain fetal tolerance. Because dendritic cells (DCs) play an important role in the initiation of immune response, we examined the effects of progesterone on the differentiation and maturation of DCs derived from mouse bone marrow cells. Our data suggest that progesterone may be involved in the maternal immune response by modulating DC differentiation, maturation and function.

The effect of acute uraemia upon the survival of skin homografts. Histological changes in the regional lymph-nodes.

The effect of acute uraemia upon the survival of skin homografts. Histological changes in the regional lymph-nodes.

Pulmonary position cryopreserved homografts: Durability in pediatric Ross and non-Ross patients

The purpose of this study was to evaluate the outcome and risk factors for implant failure in pediatric patients who underwent pulmonary position homograft placement for right ventricular outflow tract obstruction compared with conduit placement as a component of the Ross operation. Actuarial 5-year survivals for cryopreserved right ventricle-to-pulmonary artery homografts range from 55% to 94% at all ages. It is not known whether there is a difference in homograft durability when utilized for right ventricular outflow tract obstruction or as part of the Ross operation. The records of all pediatric patients receiving a right ventricle-to-pulmonary artery homograft from July 1989 through October 2003 were reviewed. Ninety-eight consecutive patients were studied (26 Ross, 72 non-Ross). In addition to Ross versus non-Ross comparisons, other potential risk factors for homograft failure analyzed included age at operation, follow-up time, type of surgery, and homograft type and size. Ross and non-Ross patients were comparable in age at the time of the operation and follow-up time. Homograft failure rates were 12% and 51% for Ross and non-Ross patients, respectively. Freedom from reintervention was 93% in the Ross and 66% in the non-Ross group at 5 years (P = .019). On multivariate analysis, non-Ross operation and age less than 2 years were significant predictors of homograft failure. 1. Pediatric patients undergoing the Ross operation have longer homograft survival than pediatric patients treated for right ventricular outflow tract obstruction, independent of age. 2. Homografts placed in patients less than 2 years of age have shorter homograft survival.

Reoperative homograft right ventricular outflow tract reconstruction

Background. Homografts are implanted in the right ventricular outflow tract (RVOT) of children, with the knowledge that reoperation might be required. We reviewed 14 years of homograft RVOT reconstruction to assess the feasibility of homograft replacement and to determine risk factors for homograft survival. Methods. From February 1985 through March 1999, 223 children (age 5 days to 16.9 years) underwent primary RVOT reconstruction with an aortic or pulmonary homograft. Of these, 35 patients underwent homograft explant at the implanting hospital with insertion of a second homograft from 2 months to 13.3 years after the first implantation. The primary operation and reoperation patient groups were compared with regard to incidence of early death, late death, homograft-related intervention without explant, and homograft explant. Results. Actuarial survival and event-free curves for initial and replacement homografts were not significantly different. Univariable analysis was performed for the following risk factors: weight ( p < 0.0001), age ( p < 0.003), homograft diameter ( p < 0.0001), homograft type ( p < 0.01), surgery date (not significant [NS]), gender (NS), Blood Group match (NS), and type of distal anastomosis (NS). Multivariable analysis of significant univariable risks revealed small homograft diameter to be a significant risk factor ( p < 0.001) for replacement. Conclusions. The RVOT homografts eventually require replacement. Patient and homograft survival for replacement homografts is similar to primary homografts. Reoperative homograft RVOT reconstruction is possible, with reasonably low morbidity and mortality.

Cryopreserved homografts in the pulmonary position: determinants of durability

Background. The cryopreserved homograft has emerged as the pulmonary conduit of choice for the repair of many congenital heart defects. It is also used for pulmonary valve replacement in the Ross procedure. Because of a wide range of patient ages and diagnoses, the risk of homograft failure may vary. Methods. We reviewed 185 consecutive pulmonary position implants performed between September 1985 and January 1999. We examined three age groups: patients less than 1 year of age (n = 53), patients 1 to 10 years of age (n = 46), and patients more than 10 years of age (n = 86). Results. Five-year Kaplan-Meier homograft survival was 25%, 61%, and 81% for the groups, respectively ( p < 0.02). Smaller homograft size, younger patient age, and truncus arteriosus were risk factors for homograft failure in univariate analysis ( p < 0.05). Smaller homograft size was the only predictor for homograft failure in multivariate analysis ( p < 0.001). Twenty of 99 implants in patients less than 10 years old underwent transcatheter intervention. The 3-year Kaplan-Meier implant survival of this group (79%) was not different from those who did not undergo intervention (77%, p = 0.84). Survival of aortic and pulmonary homografts in patients less than 10 years of age was not different ( p = 0.35). Ross procedure implants appear to have optimal survival (94%) at 5 years. Non-Ross implants in patients more than 10 years of age have 76% 5-year Kaplan-Meier survival, which is not different from Ross patients ( p = 0.33). Conclusions. Small homografts have limited durability. Aortic homografts perform as well as pulmonary homografts in young patients. Once patients receive an “adult-size” homograft, at approximately 10 years of age, risk for implant failure approximates that of patients undergoing the Ross procedure. Transcatheter interventions, when indicated, may prolong homograft life.

Expanding the kidney donor pool: Ethical and medical considerations

year later, proteinuria developed. She had an uncomplicated pregnancy in 1990. Five years later, arterial hypertension required treatment with enalapril. Her serum creatinine then was 1.2 mg/dL. The serum creatinine rose to 1.3 mg/dL two years ago and to 1.5 mg/dL last year. Earlier this year, a 24-hour urine collection contained 810 mg protein; the serum creatinine was 1.6 mg/dL and the creatinine clearance was 31 mL/min/ 1.73 m 2 . Her urine sediment was benign. A further increase in her blood pressure necessitated treatment with lisinopril, 10 mg each morning, and amlodipine, 5 mg each night. She says that she has no regrets about her decision to donate despite the outcome. Five years ago, her husband’s brother developed renal failure; with her encouragement, her husband donated a kidney. Her husband, now age 44, is in good health and has normal blood pressure, normal serum creatinine, and no proteinuria.

Infectious pulmonary disease in patients receiving immunosuppressive therapy for organ transplantation

Infectious pulmonary disease in patients receiving immunosuppressive therapy for organ transplantation

The Necessity for Steroid Induction or Long-Term Maintenance After Liver Transplantation: The Argument Against

HE question to be debated is whether our traditional reliance on steroids is relevant in the 1990s, given the new immunosuppressive modalities now available to us. The immunosuppressive properties of steroids are certainly of historic importance in the success of solid organ transplantation. As early as 1951, the efficacy of steroid immunosuppression in prolonging survival of rabbit skin homografts was demonstrated, 1 and the early success of human renal allografts was also clearly dependent on steroid therapy. However, in the modern era of improved immunosuppressive choices, it is now necessary to critically assess the balance between the immunosuppressive benefits of steroid therapy and their side effects, many of which carry significant morbidity, particularly with longterm use. Steroids exert their immunosuppressive effect by inhibition of cytokine expression. 2 This is particularly important in the direct blockade of IL1 and IL6 release from antigen presenting cells, which prevents optimal T helper cell stimulation. Steroids have also been shown to inhibit IL2, IL3, TNFa, and interferon-g, a mechanism which requires costimulation and affects activated T cells. Counterbalancing these beneficial immunosuppressive properties are the well described adverse effects of steroids, the most important of which are osteoporosis, hypertension, glucose intolerance, hyperlipidemia, obesity, and growth stunting. 3 The morbidity associated with

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

Improvements in the prevention or control of rejection of the kidney and liver have been largely interchangeable (1, 2) and then applicable, with very little modification, to thoracic and other organs. However, the mechanism by which anti rejection treatment permits any of these grafts to be “accepted” has been an immunological enigma (3, 4). We have proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenografts (5). Although such chimerism was demonstrated only a few months ago, the observations have increased our insight into transplantation immunology and have encouraged the development of alternative therapeutic strategies (6).

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

Noncardiac surgery in heart transplant recipients in the cyclosporine era

As survival and quality of life continue to improve for cardiac transplant recipients, there is an ever-increasing possibility that these patients will present for elective and/or emergency surgery outside of a transplantation center. Cyclosporine therapy has been a major factor in extending homograft survival, but recent studies have suggested that cyclosporine administration increases the duration of action of some anesthetics. The authors evaluated the influence on anesthetic management of cardiac transplantation and chronic cyclosporine therapy in a retrospective review of all postcardiac transplant patients who presented for noncardiac surgery at the study institution. The data suggest that a number of commonly used anesthetic techniques can be administered safely to these patients when no evidence of graft rejection is present. No clinically significant prolongation of anesthetic effect was encountered following the doses of anesthetics described.

Cartilage Grafts in Nasal Surgery

Cartilage grafts are being used with increasing frequency in nasal surgery, particularly with the growing popularity of open rhinoplasty. The properties of cartilage that make it a preferred grafting material are discussed as well as the historical data relating to the survival of cartilage autografts and homografts. The preferred source of cartilage grafts has been the patient's septum. This is not always feasible because of prior surgical removal or inadequate strength or size. The purpose of this paper is to describe the types of cartilage grafts commonly available for use in nasal surgery. The advantages and limitations of each are discussed. Four clinical cases are presented, demonstrating the use of septal cartilage autograft, septal homograft, irradiated rib cartilage homograft, and conchal cartilage autograft.

The Fate of Aortic Valve Homografts 12 to 17 Years After Implantation

Results of long-term follow-up of an early cohort of patients receiving aortic valve homografts for aortic stenosis and aortic insufficiency are presented. All patients were operated upon by a single surgeon from 1966 to 1971. Eighty-three patients underwent insertion of 85 homograft aortic valves. Homografts were sterilized with either betapropiolactone (39 valves) or gamma irradiation (41 valves) and were inserted following storage in nutrient medium (16 valves) or after cryopreservation (51 valves). All homograft valves were sutured in the subcoronary position using a freehand technique. There was a 55 percent 15-year actuarial patient survival and a 16 percent 15-year actuarial homograft survival in this cohort. Homograft valve failure occurred gradually allowing the patients to be observed until they developed hemodynamic compromise at which time elective valve replacement was performed.

Successful treatment of a severely burned elderly patient with homografts from her identical twin sister

A case is reported of the permanent survival of split skin homografts from the twin sister of a 65-year-old woman with 50% burns. This is the first time this has been reported in the elderly. As the homo- and autografts demonstrated the same survival pattern, the conclusion was drawn that the patient and her sister were very probably monozygotic twins. This was confirmed later by the results of the tests for HLA-typing, mixed lymphocyte studies and red blood cell antigens.

TROPHOBLAST RESTRICTION OF MATERNO-FOETAL IMMUNITY

One of the great unsolved problems in human biology today is the almost totallack of immunological understanding about the materno-foetal relationship. Genetically dissimilar tissues are normally unable to coexist, yetfoetal growth normally occurs uninterrupted with in the mother throughout gestation. This striking exception to contemporary concepts in transplantation immunology suggests that a unique mechanism developed during evolution to allow the intra-uterine development of fertilized eggs and the subsequent birth of living young, i.e. viviparity. There are also several reasons to expect that aspects of this phenomenon have been adopted by certain tumour cells to enhance their survival, and a growing body of information on certain diseases of pregnancy such as spontaneous abortion and pre-eclamptic toxaemia suggests that some of these might represent immunological imbalances between mother and foetus. There is also the hope, as yet unfulfilled, that an explanation of the mechanisms responsible for the survival of the placental homograft will be useful in organ transplantation. In order to understand the transplantation analogies of pregnancy, it is necessary to study the events which occur at the interface between mother and embryo. This interface in humans is composed of the trophob last cell membrane, and some progress has recently been made in understanding the interplay between trophoblast antigens and maternal lymphocytes with in the placental bed. Lymphocytes are normally responsible for there cognition and rejection of foreign cells, and this process can be reproduced in the laboratory by the mixed-lymphocyte culture reaction. This tool has been modified to study the interaction of lymphocytes with trophoblast antigens, thus providing a model of the materno-foetal relationship. We have used this approach during the past three years, and the results of these studies have revealed that trophoblast membranes produce a unique glycoprotein which inhibits the rejection reaction of lymphocytes while having no measurable effects on other lymphocyte reactions. This glycoprotein is species-specific and it is not found on other normal cells except amnion epithelium. Interestingly, it is however found on certain tumours such as human breast cancer cells. It thus seems as though the two major biological exceptions to immunosurveillance in natural selection, i.e. viviparity and tumour development, utilize a conon mechanism to insure their survival in potentially innunologically hostile hosts, and several aspects of this mechanism will be presented and discussed.