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Biomedical subjects

B A Reitz

Publications and source records attributed to B A Reitz.

281 records · Page 16Linked to original sources
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Improved static lung preservation with corticosteroids and hypothermia.

With methylprednisolone as a chemical inhibitor of leukocytes, extended preservation was conducted with an isolated rabbit lung model. The heart-lung blocks of 39 New Zealand white rabbits were flushed in situ with 100 ml of Euro-Collins' solution, harvested, inflated (70%), and preserved at 4 degrees C. Lungs immediately reperfused with whole blood (control lungs, group 1) were compared with lungs preserved without methylprednisolone for 5, 12, and 24 hours (groups 2 to 4) and those preserved with methylprednisolone for 12 and 24 hours (groups 5 and 6, respectively). Methylprednisolone (30 mg/kg) was administered before harvest and was used as an additive to the flush and in the blood reperfusate. Hypothermia and Euro-Collins' flush alone provided adequate preservation for up to 5 hours; however, lung edema was evident by 12 hours of cold ischemia and became severe by 24 hours. By all measured parameters, the lungs in group 5 (treated with methylprednisolone) demonstrated values equal to or better than control lungs. By 24 hours of preservation the beneficial effects of the steroid treatment were no longer evident. Histologic evaluation revealed mild to moderate injury after 5 hours of cold ischemia; progressive edema and hemorrhage were found after 12 and 24 hours of preservation. This injury was significantly ameliorated by methylprednisolone treatment at 12 hours but not at 24 hours. This study suggests that static preservation for up to 5 hours is possible with hypothermia and a Euro-Collins' flush and that extended preservation to 12 hours is possible with pharmacologic dosages of methylprednisolone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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Diagnosis of acute cardiac rejection with antimyosin monoclonal antibody, phosphorous nuclear magnetic resonance imaging, two-dimensional echocardiography, and endocardial biopsy.

A cervical heterotopic cardiac allograft model was used to compare noninvasive techniques with endocardial biopsy diagnosis of rejection. The transplant procedure was performed in eight dogs (12 to 16 kg), with a mean ischemic time of 83 minutes. Beginning on the day of the operation each allograft was evaluated daily by palpation, two-dimensional echocardiography, phosphorous nuclear magnetic resonance spectroscopy, and septal endocardial biopsy. At specific intervals after the operation, antimyosin monoclonal antibody (Fab fragment) with an indium-111 label was administered for subsequent gamma camera imaging. Rejection was clinically evident by 2 to 8 days with a mean of 3.5 days. Endocardial biopsy demonstrated moderate to severe rejection by 2 to 4 days. Two-dimensional echocardiography demonstrated early loss of wall thickening dynamics in all allografts. Although subtle changes were evident early in some transplants, these findings were not consistent. After recovery from hypothermic ischemia, evaluation of high energy phosphate metabolites with phosphorous nuclear magnetic resonance spectroscopy showed a progressive decrease in phosphocreatine during mild to moderate rejection, dropping to 30% to 40% of baseline levels with severe rejection. Antimyosin antibody uptake directly correlated with endocardial biopsy rejection scores (R2 = 0.97). With mild to moderate rejection, mean total counts and corrected counts were 222,704 and 112,648, respectively, and were significantly different (p less than 0.05) from baseline counts (135,537 and 58,530) without rejection. As a preliminary finding in untreated acute rejection, both antimyosin antibody and phosphorous nuclear magnetic spectroscopy detected changes consistent with mild to moderate rejection, which usually preceded echocardiographic evidence for injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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Differences in the pathogenesis of first-set allograft rejection and acute xenograft rejection as determined by sequential morphologic analysis.

To examine the pathogenesis of unmodified heart xenograft and allograft rejection, a sequential morphologic analysis was undertaken. Heterotopic cardiac allografts and xenografts were performed by implanting donor hearts into the abdomen of Lewis rats. Xenograft donors were Golden Syrian hamsters and allograft donors were ACI rats. Both xenografts and allografts were excised and examined by light microscopy at specific postoperative intervals. Allograft rejection was found to be a cell-mediated process, beginning with interstitial infiltrates and perivascular cuffing, which progressed to focal myocyte necroses. Ultimately, complete replacement of the myocardium by mononuclear cells was noted in fully rejected hearts. Xenograft rejection was markedly different. Although xenograft rejection was characterized first by interstitial mononuclear cell infiltrates, unlike allografts there was only minimal progression of cellular rejection. Instead, subsequent rejection was characterized by marked interstitial edema and arteriolar vasculitis and thrombosis, leading to extensive infarcts and hemorrhage in fully rejected hearts. Fibrinoid arteriolar changes and the rapid development of edema in the absence of significant cellular infiltrate suggest that cytotoxic antibodies alter xenograft vascular permeability. These data suggest that humoral immunity is largely responsible for acute concordant xenograft rejection, whereas first-set allograft rejection is mainly a cell-mediated process.

Animals↗
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Acute right ventricular failure following heart transplantation: improvement with prostaglandin E1 and right ventricular assist.

Development of significant pulmonary hypertension following orthotopic heart transplantation can result in death caused by irreversible right ventricular failure. Despite determination of acceptable preoperative pulmonary vascular resistance, this complication may still occur. This report illustrates the technique of right ventricular assist and concomitant infusion of intrapulmonary prostaglandin E1 for the treatment of postoperative right ventricular failure resulting from pulmonary hypertension.

Acute Disease↗
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Arteriolar vasculitis on endomyocardial biopsy: a histologic predictor of poor outcome in cyclosporine-treated heart transplant recipients.

The histologic pattern of severe, potentially lethal cardiac rejection in transplant recipients who are treated with cyclosporine may be difficult to distinguish from mild or moderate rejection. The purpose of this study was to determine whether specific histologic abnormalities seen on endomyocardial biopsy could identify which histologic patterns of rejection are associated with progression to graft dysfunction or graft failure. We performed a blinded, retrospective analysis of endomyocardial biopsies from our initial 19 transplant recipients. Group 1 was composed of five patients who developed graft failure or dysfunction after transplantation. Group 2 was composed of the remaining 14 patients with normal hemodynamics and function at heart catheterization 1 year after transplantation. Seventeen histologic parameters were semiquantitatively graded, and comparisons between the two groups were made with the Student's t test. Of the 17 parameters, only arteriolar vasculitis was significantly increased in group 1 versus group 2 biopsies (p = 0.002). Arteriolar vasculitis was identified in four of five patients in group 1 and was unique to group 1. Of 53 group 1 biopsies, eight patients had foci of arteriolar vasculitis and were seen up to 88 days before graft failure. Therefore the finding of arteriolar vasculitis on endomyocardial biopsy may identify high risk rejection episodes in transplant recipients who are treated with cyclosporine.

Adult↗
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Method for cardiac transplantation in corrected transposition of the great arteries.

A patient with corrected transposition of the great vessels (L-transposition) required cardiac transplantation because of severe myopathy of th systemic ventricle of right ventricular morphology. Because of the L-transposition of the great vessels, a modification of the transplantation procedure was necessary in order to make the great vessel anastomoses. This was accomplished without the need for prosthetic material primarily by extensive removal of donor pulmonary artery and aorta together with the heart. Anastomosis of the recipient ascending aorta was accomplished to the superior aspect of the transverse aortic arch of the donor, and the recipient pulmonary artery to the superior portion of the right pulmonary artery of the donor. The postoperative hemodynamics were normal and a thoracic aortogram one year post-transplant demonstrated the unusual anatomy.

Adult↗
PubMedDate not supplied

Long-term results of combined heart-lung transplantation: the Stanford experience.

We assessed the long-term results of our experience with 109 patients with end-stage cardiopulmonary disease who underwent primary combined heart-lung transplantation at Stanford University Medical Center between March 1981 and January 1994. Average recipient age was 31 +/- 10 years (mean +/- standard deviation) median, 31 years; range, 1 month to 52 years. Recipient diagnoses included primary pulmonary hypertension (31%), Eisenmenger's syndrome (39%), complex congenital heart disease (8%), cystic fibrosis (14%), bronchiectasis (2%), and emphysema (3%). Immunosuppression was with cyclosporine and a tapering regimen of corticosteroids. In 1986 azathioprine was added, and since 1987 induction therapy with OKT3 has been employed. Actuarial survival rates at 1, 5, and 10 years were 68% +/- 4.6%, 43% +/- 5.4%, and 23% +/- 8.1%, respectively (mean +/- 1 standard error of the mean). Fourteen deaths occurred in the hospital for an operative mortality rate of 12.8% +/- 3.3%, and 61 deaths occurred overall. Causes of death included hemorrhage (five patients), infection (21), rejection (one), nonspecific pulmonary failure (four), graft coronary artery disease (six), and obliterative bronchiolitis (eight). Infection, rejection, and obliterative bronchiolitis were the major complications. Only 20% +/- 3.9% of patients were free from any infection 3 months after transplantation. Heart and lung rejection commonly occurred asynchronously; actuarial estimates of freedom from isolated lung rejection at 1 and 5 years were 47% +/- 5.2% and 40% +/- 5.6%, respectively. For simultaneous heart and lung rejection these estimates were 87% +/- 3.5% and 86% +/- 3.8%, and for isolated heart rejection 63% +/- 5.1% and 51% +/- 6.4%, respectively. Although graft coronary artery disease developed less frequently than in patients after isolated heart transplantation (90% +/- 4.6% of patients were free of graft coronary artery disease at 5 years), obliterative bronchiolitis remains a major long-term complication and cause of morbidity and mortality. Actuarial estimates of freedom from obliterative bronchiolitis at 1, 5, and 10 years were 71% +/- 5.1%, 51% +/- 6.1%, and 42% +/- 7.8%, respectively. These results show satisfactory early and medium-term outcome after combined heart-lung transplantation but also underscore that much progress is needed in controlling infection, rejection, and obliterative bronchiolitis, all of which remain as major impediments to long-term survival.

Actuarial Analysis↗
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Use of theophylline for treatment of prolonged sinus node dysfunction in human orthotopic heart transplantation.

Sinus node dysfunction may complicate heart transplantation in over 50% of cases, leading to prolonged bradyarrhythmias in 20% of recipients. Permanent pacemaker implantation, the standard treatment for such persistent rhythm disturbances, can result in significant complications in this setting. A protocol with theophylline, a methylxanthine known to reverse the sinus node electrophysiologic abnormalities observed in transplant patients, was initiated at our institution in October 1989 to treat posttransplantation bradyarrhythmias and to reduce the need for pacemaker implantation. Patients with sinus or nodal bradycardia or sinus arrest were given theophylline orally; the drug was initiated in 15 of 38 patients (39.5%), 3 to 24 days after transplantation. Mean duration of treatment was 57.4 days (range, 20 to 105 days). Normal sinus rhythm with a rate of more than 90 beats/min was restored in 14 of 15 patients (93.3%). Permanent pacing was required in one patient. Transplant recipients before October 1989 (group 1, n = 112) were compared with subsequent transplant recipients (group 2, n = 38). These groups did not differ significantly in incidence of bradyarrhythmias or potential risk factors for posttransplantation sinus node dysfunction, though a greater preoperative use of amiodarone occurred in group 2. Permanent pacemaker requirement was significantly reduced from 16.1% in group 1 to 2.6% in group 2 (p < 0.05) with the introduction of theophylline. Theophylline is effective treatment for posttransplantation bradyarrhythmias, thereby resulting in a reduced need for pacemaker implantation.

Adult↗
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Leflunomide prolongs pulmonary allograft and xenograft survival.

BACKGROUND: Leflunomide, an isoxazole derivative, has been shown to effectively prolong rodent allograft and cardiac xenograft survival. In vitro studies suggest that leflunomide inhibits the production of donor-specific antibodies and is capable of blocking both T- and B-cell proliferation. In light of the significant role that humoral immunity is believed to play in chronic pulmonary allograft rejection as well as hyperacute and accelerated acute xenograft rejection, we examined the efficacy of leflunomide in prolonging pulmonary allografts and xenografts and its effect on donor-specific antibody production. METHODS: Lungs from Brown Norway rats or Golden Syrian hamsters were orthotopically transplanted into Lewis rat recipients. Allograft recipients were treated daily for 14 days with vehicle, leflunomide (15 mg/kg/day orally), or cyclosporine (7.5 mg/kg/day orally) starting on the day of grafting (day 0). In xenograft recipients, leflunomide (20 mg/kg/day orally) or cyclosporine (7.5 mg/kg/day orally) treatment initiated on day 0 was continued until complete graft rejection; the leflunomide dosage was reduced to 10 mg/kg/day after day 14 because of weight loss and leukopenia. Graft viability was assessed with chest radiography in conjunction with open lung biopsies. Toxicity was monitored with body weight measurements, complete blood counts, and serum chemistries. Flow cytometric analysis of serum samples taken from graft recipients on day 7 was used to measure donor-specific immunoglobulin M and immunoglobulin G antibody titers. RESULTS: Allograft and xenograft control animals receiving vehicle yielded graft survival times of 6.0 +/- 0.0 and 5.4 +/- 0.6 days, respectively. Although xenograft recipients treated with cyclosporine (7.5 mg/kg/day orally) showed no significant graft prolongation, pulmonary allograft survival in recipients receiving cyclosporine alone was significantly prolonged to 28.2 +/- 0.7 days. Leflunomide-treated allograft (15 mg/kg/day orally) and xenograft (20 mg/kg/day orally) recipients displayed significant graft prolongation to 28.2 +/- 0.7 days and 15.8 +/- 3.3 days, respectively. Cyclosporine (7.5 mg/kg/day orally) enhanced the effect of leflunomide (20 mg/kg/day orally) in xenograft recipients with a mean graft survival time of 36.0 +/- 3.0 days achieved when both drugs were administered concomitantly. Cyclosporine significantly suppressed donor-specific immunoglobulin G antibody titers in both pulmonary allograft and xenograft recipients while not affecting immunoglobulin M levels. Leflunomide markedly suppressed both immunoglobulin G and immunoglobulin M donor-specific antibody titers in allograft and xenograft recipients. Except for mild leukopenia and anemia, both cyclosporine- and leflunomide-treated allograft recipients showed no evidence of toxic side effects after 14 days of therapy. However, leflunomide-treated xenograft recipients displayed significant weight loss, anemia, and leukopenia after 14 days of treatment with one death in each treatment group.

Administration, Oral↗
PubMedDate not supplied

Heart retransplantation: the 25-year experience at a single institution.

BACKGROUND: The current critical shortage of cardiac allograft donors means that the decision to offer a patient repeat heart transplantation must be carefully considered. Since 1968, a total of 66 heart retransplantation procedures (63 first-time and three second-time) have been performed in 63 patients at Stanford. METHODS: There were 52 male and 11 female patients, ranging in age from 3 to 62 years with a mean age of 41 years. Indications for retransplantation were primary allograft failure in nine patients, acute rejection in 17, graft atherosclerosis in 37, and constrictive disease in three. Six of the seventeen patients (35%) who underwent retransplantation before 1981 died in the hospital, and none are currently alive. Of the 46 patients who underwent retransplantation since 1981 treated with cyclosporine-based immunosuppression, 11 (24%) died in the hospital. Actuarial survival estimates for the whole retransplantation group at 1, 5, and 10 years were 55% +/- 8%, 33% +/- 8%, and 22% +/- 7%, respectively. RESULTS: This survival was significantly worse (p < 0.05) than that in patients undergoing primary heart transplantation (81% +/- 2%, 62% +/- 2%, 44% +/- 13% at 1, 5, and 10 years). Those patients who underwent retransplantation for graft atherosclerosis since 1981 had a significantly better 1-year survival (p < 0.05) than those who underwent retransplantation for allograft rejection (69% +/- 10% versus 33% +/- 16%), but the 5-year survival was similar in both groups (34% +/- 11% versus 33% +/- 16%). Since 1981, actuarial freedoms from infection and rejection were 22% +/- 8% and 41% +/- 9%, respectively, at 1 year, and 7% +/- 7% and 36% +/- 9% at 5 years. Patients with cyclosporine-induced renal dysfunction (serum creatinine level of greater than 2.0 mg/dl) had a high probability of requiring postoperative dialysis and also of death after retransplantation. Three patients with significant cyclosporine-induced renal dysfunction underwent simultaneous kidney transplantation and heart retransplantation, and all were alive and well at the time this article was written. Sixteen patients were also currently alive at a mean follow-up of 44 months, and 15 were in New York Heart Association functional class I. CONCLUSIONS: We continue to list carefully selected candidates with good rehabilitation potential for heart retransplantation.

Actuarial Analysis↗