Biomedical subjects

C L Backer

Publications and source records attributed to C L Backer.

111 records · Page 7Linked to original sources

PubMedDate not supplied

A new rat infection-heart transplant model: effect of infection on graft survival studies.

Considerable progress has been made in survival rates of heart transplant recipients; however, infections continue to be a major cause of death after transplantation. Although infection itself appears to cause immunologic suppression in some nontransplantation studies, the lack of an infection-transplant animal model has limited further investigation of this observation. We evaluated the utility of a heterotopic rat infection heart-transplant model by studying the effect of infection and limited administration of two immunosuppressive agents, cyclosporine and FK506, on allograft rejection and survival. Lewis rats received ACI heart allografts, and intraperitoneal infection was induced by cecal ligation. Infection was confirmed by blood and ascitic fluid cultures. Results showed that graft survival was slightly, but significantly, higher (p < 0.05) in group II (transplantation with infection) when compared to the control group I (transplantation only). Histologic rejection scores were less (p < 0.05) in group II 6 days after transplantation. The second phase of the study compared the effect of infection after transplantation in rats given a 1-week course of cyclosporine or FK506, which were discontinued after the induction of infection. Although the cyclosporine group had prolonged survival when compared to the FK506 group (p < 0.05), the respective infection groups receiving immunosuppression revealed no significant difference in allograft survival or histologic rejection scores when compared to the control groups. In this preliminary study, infection without immunosuppression resulted in a slight, but statistically significant, increase in allograft survival and reduced acute cellular rejection. In those groups receiving immunosuppressive agents, no additive immunosuppressive effect was attributable to bacterial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Pharmacologic reduction of pretransplantation pulmonary vascular resistance predicts outcome after pediatric heart transplantation.

Pulmonary hypertension leading to donor right ventricular dysfunction remains a major risk factor associated with poor outcome after heart transplantation. This study evaluated a pretransplantation protocol to assess pulmonary vascular resistance index and its response to pharmacologic modulation. Cardiac catheterization was performed in 25 patients (mean age, 8.6 years [range, 1 to 17 years]; mean weight, 27.3 kg [range, 8.1 to 54 kg]) with end-stage heart failure. Mean pulmonary artery and capillary wedge pressures and cardiac index were measured in the baseline state and during administration of 100% oxygen, dobutamine at 10 micrograms/kg/min, and nitroprusside at 1 to 4 micrograms/kg/min. Transpulmonary pressure gradient and pulmonary vascular resistance index were calculated. In 22 survivors, hemodynamics were reassessed 1 and 4 weeks after transplantation. The mean cardiac index significantly increased (2.2 to 3.2 L/min/m2); transpulmonary pressure gradient (12.7 to 9.6 mm Hg) and pulmonary vascular resistance index (6.2 to 3.0 units/m2) decreased during the drug study. In 12 patients with a baseline pulmonary vascular resistance index of more than 6 units/m2, 10 survived heart transplantation. This study shows that pharmacologic reduction of the pulmonary vascular resistance index in the pretransplantation protocol predicts reduced pulmonary vascular resistance index and a favorable outcome after heart transplantation.

Adolescent↗

PubMedDate not supplied

Spectrum of humoral rejection after pediatric heart transplantation.

The deposition of immunoglobulin and complement 3 in the coronary microvasculature (humoral rejection) has been associated with poor outcome after heart transplantation. The purpose of this study is to relate the incidence of immunoglobulin and complement 3 myocardial deposition to the clinical course of pediatric heart transplant patients. One hundred thirty-one biopsy specimens from 30 patients, whose mean age at transplantation was 4.9 years (range, 2 days to 17 years), were processed for light microscopy and immunofluorescence. The mean follow-up was 25 months (range, 6 to 63 months). All patients underwent annual selective coronary artery angiography. No cellular or humoral rejection was seen in 97 biopsy specimens. Humoral rejection without cellular infiltrate was found in eight biopsy specimens from four patients (13%). Of 19 grade 1A, B (mild) biopsy specimens, 17 showed only cellular rejection, and two showed a mixed pattern of cellular and humoral rejection. Of six grade 2,3 (moderate) biopsy specimens, four showed only cellular rejection, and two showed a mixed pattern. The only grade 4 (severe) biopsy specimen revealed a mixed pattern. Three patients have had persistent immunoglobulin M and complement 3 deposits. One of these had angiographic evidence of accelerated graft coronary artery disease 2 years after transplantation, which was later confirmed at autopsy. Coronary artery disease has not been detected by serial angiography at 1 year (28 patients), 2 years (18 patients), 3 years (15 patients), 4 years (five patients), and 5 years (one patient). Humorally mediated rejection occurs with and without cellular rejection after pediatric heart transplantation. Humoral rejection may persist after treatment and resolution of severe cellular rejection episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗