Assessment of the longevity of the liver using a rat transplant model

BACKGROUND: Our goal was to study the long-term follow-up of patients having aortic valve replacement and to focus particularly on the patients receiving small prostheses. METHODS: Four hundred twenty-eight Medtronic-Hall valves were implanted (156 size 20 or 21 mm, 149 size 22 or 23 mm, and 123 size 25 or 27 mm). Group 20-21 had a higher number of female patients, more associated coronary lesions, and more patients with aortic stenosis. RESULTS: The actuarial survival rate at 8 years was 80% for group 20-21, 80% for group 22-23, and 76% for group 25-27 (p = not significant). In group 20-21, the actuarial event-free rates at 8 years were as follows: thromboembolic complications, 94%; prosthetic valve endocarditis, 99%; reoperation, 98%; and hemorrhagic complications, 78%. The only factors of prognostic value in this group were age and associated coronary lesions. CONCLUSIONS: The durable nature of the results obtained with the Medtronic-Hall 20- and 21-mm prostheses compared with large-diameter prostheses allows the use of a simple and reliable surgical technique and should mean that indications for ring enlargement become rare.     

Interpretation of biopsy findings in the transplant liver

With several thousand liver transplants being performed each year and many patients being managed in their local medical centers, much of the interpretation of transplant liver biopsy specimens has moved from the transplant hospital to the community setting. This article discusses both typical and more peculiar changes that occur in the transplant liver biopsy specimen. Accurate interpretation requires clear knowledge of these possible changes as well as knowledge of clinical data, such as time elapsed since transplantation and the patient's primary disease.     

Tuberculosis in liver transplant patients

Beta human chorionic gonadotrophin levels have been assessed in blood serum of 79 patients with bladder tumours before and seven days after transurethral electroresection (TUR). With the growth grade of anaplasia and staging the mean serum beta HCG level increased. Beta HCG was a good biological marker to differentiate between superficial and deep tumours.     

Development of a mouse aortic transplant model of chronic rejection

Chronic rejection is the most common cause of late graft failure after solid organ transplantation. A model of chronic rejection, the rat aortic allograft, has histologic features that parallel those in the vessels of human transplanted organs. However, the molecular tools required to dissect the immunology of chronic rejection are unavailable in the rat. We developed aortic transplantation in the mouse as a new model of chronic rejection. This will allow the use of the diversity of recombinant cytokines and monoclonal antibodies available for the mouse and its well-defined genetics to investigate chronic rejection in greater detail. We describe the perioperative care and surgical technique for the model in which a 1 cm segment of donor thoracic aorta was used to replace a section of recipient abdominal aorta below the renal arteries and above the aortic bifurcation. Mortality rates were initially high (70%) due to thrombosis and shock. Changes in technique and operator facility resulted in a high rate of success (75%). After 192 operations, the current success rate is > 80%. Mice free from complications at 12 hrs postop had indefinite survival, and after 2 months the typical vascular lesion of chronic rejection was present. This new model of chronic rejection will be a valuable tool to study the molecular immunology and genetics of chronic rejection.     

Diastolic dysfunction coincides with early mild transplant rejection: in situ measurements in a heterotopic rat heart transplant model

BACKGROUND: Diastolic dysfunction seen in early clinical transplant rejection has been difficult to demonstrate in experimental rodent models because of the inability to make sensitive in situ measurements of systolic and diastolic functions. We have developed a heterotopic heart transplant model with Fisher 344 and ACI rats (without immunosuppression), where in situ measurements of diastolic and systolic functions were made sequentially (daily) by use of an implanted left ventricular balloon. METHODS: Syngeneic and allogeneic heterotopic heart transplants were performed. In situ function was determined by varying balloon volume to measure the developed pressure, the rates of pressure rise (+dp/dt) and pressure fall (-dp/dt), diastolic pressure-volume relationship, and the time constant of diastolic relaxation (tau). These results were compared with function measurements in transplanted hearts that were excised and perfused in a Langendorff mode (ex vivo) during the same posttransplantation period. RESULTS: Histologic examination revealed that at day 3 after transplantation, allografts showed mild lymphocytic infiltration indicative of mild or early rejection, and by day 5, there was severe rejection with myocyte necrosis. By day 3, the slope of the diastolic pressure-volume relationship (ie, left ventricular stiffness) was significantly higher in allografts as compared with isografts (436 +/- 96 vs 177 +/- 26 mm Hg/mL, p < .05). Similarly, tau was significantly longer in allografts by day 3 after transplantation. Developed pressure and +dp/dt became significantly lower in allografts beginning on day 6. Function measurements made in the isolated perfused ex vivo hearts yielded the same results at day 3 after transplantation as the in situ group of hearts. CONCLUSION: Using a chronically implanted left ventricular balloon, we have developed a heterotopic heart transplant model where sensitive measurements of systolic and diastolic functions can be made. With this preparation, the early changes in the diastolic dysfunction seen clinically can be reproducibly detected. Thus this model may be useful to study mechanisms and interventions during early transplant rejection.     

Infection complicating percutaneous liver biopsy in liver transplant recipients

There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection. The medical records of all patients undergoing OLT between January 1990 and August 1994 were reviewed retrospectively to identify complications requiring hospitalization within one week of percutaneous liver biopsy. The nature and severity of complications were recorded and possible risk factors for infectious complications were examined. One hundred ninety-eight patients underwent 1,136 percutaneous liver biopsies. There were eleven complications (0.96%), including as follows: 7 infections, 3 bleeding episodes, and 1 vasovagal reaction. Infections after percutaneous liver biopsy included fever and bacteremia (n = 6), and fever without bacteremia (n = 1). All infections developed only in patients with underlying biliary tract abnormalities; the frequency of infection was higher (9.8%) in patients with choledochojejunostomy when compared with those with choledochocholedochostomy (1.4%). Bacteremia was more likely caused by skin flora in patients with choledochocholedochostomy (CDC) and by enteric bacteria in patients with choledochojejunostomy (CDJ). All infections were treated successfully with parenteral antibiotics. We conclude that biliary tract abnormalities are the primary risk factors for infection after percutaneous liver biopsy, although the risk is higher in patients with CDJ than with CDC. These data support the use of antibiotic prophylaxis before percutaneous liver biopsy in OLT recipients with biliary tract abnormalities.     

Current concepts in pediatric liver transplant

Orthotopic liver transplantation has significantly improved the survival rate of children with end-stage liver disease. Efforts to correct abnormalities existing prior to transplantation coupled with improved surgical techniques and immunosuppression have led to better quality of life and 1-year survival rates approaching 90% in many centers. Despite this success the expanding waiting list population of all ages has driven development of operative techniques to expand the donor pool. Building on the success of reduced-size transplantation, split-liver and living-donor transplantation are now suitable alternatives, especially when used in candidates with satisfactory clinical stability. In the post-operative period, infectious complications represent an important cause of morbidity and mortality. Although antimicrobial regimens are effective in the immediate post-operative phase, acquisition of viral infections represents a major concern particularly in the young liver recipient. Early detection and development of new anti-viral agents are likely to decrease occurrence of post-transplant proliferative disorders and optimize longterm transplantation outcome.     

Endoscopic retrograde cholangiopancreatography in the orthotopic liver transplant patient

BACKGROUND AND STUDY AIMS: Diagnostic imaging of the biliary tract is often required in liver transplant recipients, preoperatively to assess extent of biliary tract disease and postoperatively in patients with a suspected biliary complication due to an abnormal postoperative course. PATIENTS AND METHODS: Over a six-year period, 115 patients received 127 liver transplantations at our institution. Twenty-three preoperative ERCPs were performed in 17 patients, while 25 ERCPs were performed on 15 patients after liver transplantation. RESULTS: Preoperative ERCP in seven of 17 patients revealed a dominant biliary stricture as a result of primary sclerosing cholangitis (PSC); five of these patients were managed successfully with the placement of biliary endoprosthesis. An additional nine patients with PSC underwent brush cytology of the extrahepatic bile ducts to rule out coexisting cholangiocarcinoma; there were no positive results, although three were found to have coexisting cholangiocarcinoma after examination of the explanted liver. Postoperatively, nine of 15 patients were found to have biliary tract disease. These included five biliary strictures (three treated successfully by endoscopic dilation and stent therapy), two biliary leaks (treated by biliary endoprosthesis), one biloma (treated by percutaneous drainage) and one intraductal stone (treated successfully by sphincterotomy and stone extraction). The remaining six patients showed no abnormality at ERCP, and were subsequently diagnosed with allograft rejection. CONCLUSIONS: Diagnosis of biliary complications after hepatic transplantation is often problematic. Definitive characterization frequently requires cholangiography. Interventional biliary procedures, both endoscopic and percutaneous, can be used successfully to treat these complications; however, surgical revision and retransplantation are sometimes required.     

Detection of benzoquinone adducts to rat liver protein sulfhydryl groups using specific antibodies

Benzoquinone is an electrophilic metabolite of bromobenzene and other simple aromatic compounds of toxicological interest including benzene, phenol, hydroquinone, and acetaminophen. In reacting with proteins benzoquinone shows great selectivity for Michael addition to sulfhydryl groups and formation of S-(2,5-dihydroxyphenyl) protein adducts. To facilitate the specific detection and eventual isolation and identification of such adducted proteins, we prepared an antiserum capable of recognizing hydroquinone moieties by immunizing rabbits with keyhole limpet hemocyanin modified with 3-[2,5-dihydroxyphenyl)thio]propanoyl groups as haptens. The antiserum had a high titer and showed high specificity for hapten in competitive ELISA with hapten analogues. In Western blot experiments the antiserum detected not only synthetically haptenized control proteins but also several proteins from rat liver microsomes that had been incubated in vitro with [14C]bromobenzene. This binding was completely blocked by free hapten, showing that it was hapten-specific. Each of the microsomal protein bands detected in the Western blots also contained radioactivity, but not all radioactive protein bands reacted with antibody. This antiserum should prove useful in exploring the role of protein arylation by benzoquinone in cytotoxic responses to its metabolic precursors.