Biomedical subjects
Publications and source records attributed to R J Fischel.
The management of children's tumors has changed significantly in the past several years. New techniques and combined surgical, chemotherapeutic, and radiation approaches are responsible for improved survival in most instances. Cooperation of the surgeon with the specialists in separate disciplines is imperative to continued advancements in neoplastic disease of childhood.
Transplantation of immediately vascularized grafts across species barriers in which preformed cytotoxic antibodies exist, otherwise known as discordant combinations, has uniformly resulted in hyperacute rejection. We studied how well plasma exchange and perfusion through organs removes preformed immunoglobulin M cytotoxic antibodies and prolongs survival of a porcine heart heterotopically transplanted into a rhesus monkey. With the use of plasma exchange or absorption of antibodies by porcine kidney perfusion with or without immunosuppression, graft survival was prolonged, although antibody-mediated rejection ultimately occurred. In one case in which plasma exchange, kidney perfusion, and immunosuppression were combined, a functioning pig heart survived in a rhesus monkey for 8 days without evidence of rejection. The animal was killed on day 8 according to protocol because of a wound dehiscence. With this animal we were able to demonstrate that circulating antibodies against graft endothelium had bound to the graft endothelium without inducing rejection, a process referred to as accommodation. In this case, despite the presence of antiendothelial antibodies, complement did not appear to be activated, and fibrin thrombi did not form. Although we have achieved this rejection-free survival only in one animal, this case suggests that it may be possible to maintain xenotransplants in discordant species without rejection if preformed antibodies are appropriately lowered or altered during the initial period of graft implantation.
The ability of an on-line, rapid plasma exchange (PE) system to remove circulating antibodies in preparation for xenogeneic heart transplantation was studied. Plasma exchanges were performed 27 times on 13 rhesus monkeys weighing from 6.5 to 12.0 kg, using systemic heparinization, without untoward effects. Blood flow rates of 22-72 ml/min resulted in plasma collection rates of 7-22.5 ml/min. Serum immunoglobulin levels were decreased by more than 90%, and specific antiendothelial xenoreactive IgM was completely removed after two plasma exchanges. Transferrin levels were decreased 85-95%, and complement levels fell by greater than 80%. Platelets were partially conserved, with removal rates of 18-60%. All factors returned to normal ranges within 48 hours and no bleeding complications were encountered. When antiendothelial antibodies were removed in this manner, survival of a pig heart transplanted into a rhesus monkey was extended to 12 hours, from a baseline of 2 hours, without treatment.
The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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The physiologic effects of 12-hour lung preservation were assessed in six mongrel dogs studied for 20 hours after double-lung allograft implantation. Donor animals were pretreated with allopurinol (30 mg/kg) and methylprednisolone (500 mg) intravenously at anesthesia induction. Heart-lung blocks were harvested after cardioplegic arrest, and a simple pulmonary artery flush of 4 degrees C modified Collins' solution was administered at 15 ml/kg/min. The lungs were ventilated with 100% nitrogen during flushing and inflation. Recipient animals received an infusion of deferoxamine (20 mg/kg) during implantation and were pretreated with methylprednisolone (500 mg) intravenously. All six implantations were technically successful. Two animals died of cardiac standstill 12 and 24 hours postoperatively. Gas exchange deteriorated after implantation compared with donor levels but remained in a range compatible with survival, and at 20 hours arterial oxygen tension (FiO2 0.4) was 138 +/- 91 mm Hg. Similar changes were seen in alveolar-arterial oxygen gradients and arterial-alveolar oxygen tension fraction. Elimination of carbon dioxide was satisfactory. Pulmonary venous shunt fraction rose significantly at the end of the study. Hemodynamic changes consisted of a gradual increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated, with a gradual rise in airway resistance and a fall in compliance. The double-lung model allows detailed assessment of the early effects of preservation and may have certain advantages over heart-lung models of preservation. The preservation technique warrants further study.
Recent developments in the field of blood component separation have revealed the usefulness of membrane filtration using couette type configurations and Taylor vortices as an efficient and effective method. The authors have analyzed in detail the physical and chemical effects on whole blood separated into protein rich plasma, and concentrated red blood cell suspensions, using this technique. The authors also have calculated and demonstrated the technical specifications required to provide laminar flow with Taylor Vortex formation throughout the device, as well as those required to retain constant shear stress on the blood components as viscosity changes. By maintaining constant shear stress below a critical level, it is possible to avoid shear induced hemolysis and to maintain maximal separation efficiency throughout the procedure. The device has further been designed to alter the filtration velocity along the membrane so that the critical filtration velocity is nowhere exceeded, i.e., concentration polarization effects are prevented.