Session IV: Surgical techniques in pediatric heart transplantation.
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Biomedical subjects
Publications and source records attributed to C Mavroudis.
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Tetralogy of Fallot and absent pulmonary valve (T-APV) is associated with massively dilated pulmonary arteries that cause tracheobronchial compression in the newborn and heart failure and cyanosis in older patients. Corrective operations have been attended by high mortality rates due to pulmonary insufficiency causing right heart failure (RHF) and pulmonary complications. Pulmonic valve insertion (PVI) with complete repair has resulted in improved survival. During the last 5 years, 152 patients with tetralogy were corrected. Of these, 10 patients (ages 51 days to 34 years) had absent pulmonary valve. One patient (age 51 days) presented with severe RHF and pulmonary insufficiency and 9 patients presented with mild RHF and cyanosis. Chest roentgenograms showed increased cardiothoracic ratio and pulmonary prominence in all. Arteriography revealed massively enlarged pulmonary arteries with a mean ratio of 2:1 for size of pulmonary artery to aorta. Associated pulmonic stenosis and insufficiency was present in all. Seven patients underwent closure of ventricular septal defect (VSD) and PVI. Of these, 3 had PVI (2 tissue and 1 prosthetic) with outflow patch and 4 had right ventricle to pulmonary artery (RV-PA) tissue valved conduits. Two patients had repair without PVI, and 1 had repair with a monocusp pericardial valve patch. Nine patients have done well with no episodes of thromboembolism or infection. Death occurred in a 51-day-old infant who had VSD closure and relief of pulmonic stenosis. Pulmonary valve insertion seems to be indicated in these patients because it lowers peak pulmonary artery pressure and, thus, reduces compression effects on the trachea and bronchi. When PVI was used, RHF did not occur post-operatively.
BACKGROUND: Clinical studies have reported increased rejection in female heart transplant recipients. Conflicting data exist as to whether rejection is increased with male donors or female donors in these female recipients. METHODS: We investigated in this study allograft rejection in four sets of gender combinations with and without immunosuppression with the use of a heterotopic rat heart transplant model: male donor heart to female recipient, female donor heart to female recipient, male donor to male recipient, and female donor to male recipient. To examine the possible effect of androgens as an immunosuppressant, we orchiectomized a group of male recipient rats before transplantation. The rats that were not immunosuppressed were evaluated for length of graft survival (palpation). In the immunosuppressed rats (cyclosporine, 10 mg/kg x 7 days) in each gender combination half of the grafts were evaluated for length of survival (palpation) and half for cellular rejection grade at day 14 (microscopy). RESULTS: When rats that underwent transplantation were not immunosuppressed, no difference in graft survival time was found among the four sets of gender combinations. With immunosuppression, median graft survival time was 23 days in female recipients versus 32 days in male recipients (p < 0.05). Mean cellular rejection grade at day 14 was 2.95 +/- 0.7 in female recipients and 0.8 +/- 0.4 in male recipients (p < 0.01). No significant difference was found in graft survival time or cellular rejection grade with respect to donor gender. The graft survival times and cellular rejection grades of the male rats undergoing orchiectomy were not different from those of normal male recipients (p = NS). Cyclosporine levels on day 7 in both male and female recipients were high, female levels (1039 +/- 411 ng/ml) were less than male levels (2029 +/- 379 ng/ml) (p < 0.01). CONCLUSIONS: Female recipients of heterotopic rat heart transplants had shorter graft survival time and increased cellular rejection as compared with male recipients. Donor gender had no influence on graft survival or cellular rejection grade. Orchiectomy had no influence on graft survival time or grade of rejection. Results of this model suggest that female recipients may require increased immunosuppression and rejection surveillance, regardless of donor gender.
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)
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.
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)