Orthotopic heart transplantation in a transgenic pig-to-primate model

BACKGROUND: Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS: Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS: Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS: The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.     

Observations of nodule growth during the oxidation of pure binary iron-aluminum alloys

Oxidation studies were carried out in oxygen at 800°C, on a series of pure binary iron-based alloys with between 1.9 and 9.8 wt. % aluminum. The results are presented in conjunction with the existing literature and these permit the development of a classification of scale morphologies based on alloy composition. Alloys with less than about 2.4 wt. % aluminum form bulky stratified scales composed of Fe₂O₃ and Fe₃O₄ with FeAl₂O₄ and Al₂O₃ at the scale-metal interface. Alloys with between 2.4 and 6.9 wt. % form an external Al₂O₃ scale but this is interspersed with iron oxide nodules that penetrate the alloy substrate. Only alloys with greater than 6.9 wt. % aluminum form completely protective Al₂O₃ scales. Models based on oxide nucleation are presented for the growth of bulky scales and also the iron oxide nodules.     

The oxidation of high-purity iron-chromium-aluminum alloys at 800°C

A systematic study is presented of the oxidation of pure iron-chromium-aluminum alloys at 800°C, in pure oxygen, at a pressure of 200 Torr. Oxidation characteristics are described with reference to kinetic measurements, scale topographies and morphologies, and also possible growth mechanisms. An oxide map is used to show that alloys may be classified into four categories depending on the external scale that forms: Fe₂O₃, Cr₂O₃, Al₂O₃, or Al₂O₃ with iron-oxide nodules. Alloys containing less than 2–2.5 wt. % aluminum formed either Fe₂O₃ or Cr₂O₃ as an external scale, depending on the chromium content, and internal, rod-like protrusions of Al₂O₃. At higher aluminum concentrations, Al₂O₃ was always present as an external scale, although this was interspersed by iron-oxide nodules at chromium concentrations of less than 5 wt. %. A model based on Wagner's secondary getter concept is proposed for eliminating nodule nucleation. Evidence is also present that indicates that at 800°C, alumina scale decohesion occurs prior to void formation and that voids are the result of thermal etching beneath lifted scales.     

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.     

<Emphasis Type="Italic">In Situ</Emphasis> Observation of Strain Evolution in Cp-Ti Over Multiple Length Scales

The strain evolution in polycrystalline CP-Ti strip under tension was studied in situ and at two length scales using Synchrotron X-ray diffraction. To establish the bulk material behavior, experiments were performed at the Australian Synchrotron facility. Because of the relatively large grain size, discontinuous “spotty” Debye ring patterns were observed, and a peak fitting algorithm was developed to determine the individual spot positions with the necessary precision for strain determination. The crystallographic directional dependence of strain anisotropy during the loading cycle was determined. Strain anisotropy and yielding of individual crystallographic planes prior to the macroscopic yield point were further clarified by in situ loading experiments performed at the Advanced Light Source (ALS). The deviatoric strain accumulation and plastic response were mapped on a grain-by-grain basis. The onset of microscopic yielding in the grains was identified and correlated with the relative orientation of the grains with respect to the loading direction.     

The oxidation of binary iron-manganese alloys

Oxide scales formed on iron-manganese alloys are generally considered to be similar to those formed on the parent metals. Metallographic examination is used in conjunction with EMPA, XRD, and X-ray imaging to reveal the presence of the additional phases Mn₂O₃ and Mn₃O₄ in the scales formed on binary alloys containing up to 40% manganese at 700 and 800°C in 200 Torr oxygen. A mechanism is proposed to explain the apparent change in growth from iron-rich to manganese-rich scales during oxidation of Fe-40Mn at 800°C.     

The acute abdomen following cardiopulmonary bypass surgery

Over a 5-year period, 9 patients (0.85 per cent) developed a major acute abdominal complication after cardiopulmonary bypass surgery. Difficulties in the initial recognition and diagnosis of these complications in sedated, ill patients are highlighted. A high index of suspicion is important in the early diagnosis of these complications. The numbers are too small for statistical analysis, but experience suggests that each case should be dealt with on its merits in accordance with common surgical practice and that operative management should not be rejected because the patient has recently undergone a major cardiac operation.     

Mapping of the oxidation products in the ternary Co-Cr-Al system

The kinetics and products of oxidation of alloys in the Co-Cr-Al system have been studied and four mechanisms of oxidation identified. For the first mechanism, the rate-controlling process is cation diffusion of cobalt cations through CoO, and the main oxidation product is CoO. In the second mechanism, cation diffusion through CoO is still rate controlling, but the oxidation is strongly inhibited by an inner discontinuous spinel layer. The major oxidation products are CoO and CoCr₂O₄. The third mechanism of oxidation consists of preferential oxidation of chromium coupled with internal oxidation of aluminum while the fourth mechanism is the preferential oxidation of aluminum with the subsequent formation of Al₂O₃ scales, providing the best oxidation resistance. From the oxidation data obtained, an oxide map from which the oxidation behavior of various alloys may be deduced is drawn for the Co-Cr-Al system at 1100°C.