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Biomedical subjects

J V Cockrell

Publications and source records attributed to J V Cockrell.

17 recordsLinked to original sources
PubMed1978

Host response to allogeneic implants in the anterior chamber of the rat eye.

The anterior chamber of the eye has long been considered an immunologically privileged site, but the nature of this privilege has been re-examined recently. In our study, we used rats with defined genetic differences as the donors and the recipients. Implants were from split-ear sections, and the host response was measured both in vivo, by implant survival time, and in vitro, by the mixed-leukocyte reaction and the 51Cr-release cytotoxicity assay. Controls consisted of syngeneic implants and allogeneic orthotopic skin grafts. This study has shown that (1) host sensitization occurs approximately 7 days after implantation, (2) cytotoxic effector cells are produced by day 14, with a peak on day 21, (3) implant survival time is long in spite of the presence of competent effector cells, and (4) the survival time of implants is directly related to the degree of genetic histoincompatibility. The reasons for the long implant survival in hosts with a demonstrable immune reactivity has not been established, but the survival time appears to be related to the route of sensitization (vascular rather than lymphatic), which lends itself to the production of serum blocking factors and the procurement of supressor T cells.

Animals↗
PubMed1975

One 25 day survivor with total artificial heart.

One calf, which weighed 87 kilograms, survived for 25 days with a total artificial heart (TAH) implanted orthotopically. All hemodynamic parameters stayed normal except the right atrial pressure (RAP), which increased gradually toward the end of the experiment. The cardiac output was maintained between 8.0 and 11.0 L. per minute. Kidney function was well maintained, and no pulmonary insufficiency was noted. Infection became obvious after 2 weeks of pumping although it was controlled to the extent that the calf was able to eat, to several factors, amont them mechanical damage to red blood cells, infection, malnutrition, and liver damage. The calf was standing until 30 minutes before its sudden death from cerebral thromboembolism. The calf's activity throughout the postoperative course convinced us of the feasibility of clinical application and of immediate application to studies of cardiovascular physiology and pharmacology.

Animals↗
PubMed1975

Refinement in application of total artificial heart, with improvement in survival and histopathological findings.

Recent improvements in total artificial heart (TAH) experiments have changed the pathological findings as well as the concept of the TAH. In the past 3 years, 67 experiments were performed in our laboratory. This study concerns the 11 calves operated upon most recently. Histopathological findings in the lungs, kidneys, livers and spleens of these animals were greatly improved over findings from previously studied animals. Disseminated intravascular coagulation (DIC) syndrome has been seen in only 1 calf. These improvements can be attributed to the following factors: (1) Improved management of the lumg during surgery has essentially eliminated pulmonary insufficiency;(2) liver damage has been successfully prevented by the discovery of the relationship between high right atrial pressure and anemia; (3) careful aseptic surgical procedures and optimal prophylactic use of antibiotics and anticoagulants have minimized the incidence of infection and clot formation.

Animals↗
PubMed1974

Organ specificity in hyperacute rejection of canine heart and kidney allografts.

To clarify the organ specific nature of hyperacute rejection, 14 puppies were presensitized by multiple skin grafts and spleen cell injections prior to receiving either a heart or kidney allograft from the respective donors. Of this group, 7 received orthotopic heart allografts and 7 received kidney allografts. All heart allografts were rejected between 3 and 28 hours, and all kidneys between 0 and 24 hours as judged by cessation of urine flow from the ureterostomies. In contrast, all 11 animals in a recent series of heart allografts in non-sensitized puppies survived the operation, and rejected between 7 and 17 days. There was a significant correlation in both groups between preoperative cytotoxic antibody titer in the recipient serum and graft survival time. The preoperative titers were all above 1:1,024 but were greatly reduced within 2 hours after transplantation. At the time of rejection, antibody could be eluted from the rejected organs. In contrast to the kidneys, in which 2 of 7 grafts ceased to function immediately after revascularization, all hearts resumed beating and functioned well for at least several hours. At autopsy, the myocardium was pale and edematous and histologically polymorphonuclear leukocytes were prevalent in and around the small vessels and among myofibers. Both IgG and IgM antibody was detected in sarcolemma of the myocardium and to a lesser extent in the intima and adventitia of the small vessels by the fluorescent antibody technique. Biopsies of the rejected kidneys showed polymorphonuclear leukocyte infiltration, typical of hyperacute rejection. Marked fluorescence of IgG and IgM in the glomeruli and peritubular capillaries was observed. This study indicates that both organs rejected hyperacutely in our experimental model and participation of the preformed antibody in effecting this change was strongly suggested.

Animals↗
PubMed1974

Histopathology of one-stage bilateral lung allografts.

Morphological features of modified and unmodified bilateral lung allografts were studied in 87 dogs. Immunosuppressive treatment consisted of various combinations of azathioprine, methotrexate, prednisolone, methylprednisolone and antilymphocyte serum. The classic acute rejection was observed in the unmodified dogs, which died between 4 and 9 days. Progression of the lesion was confined to a certain stage in these lung allografts charged with providing total pulmonary function, so that hemorrhagic necrosis was never encountered. Immunosuppressive drugs decrease the speed and intensity of classic rejection, and increase the complications of respiratory infection in the protracted course. Of 14 dogs surviving more than 14 days, 4 died of chronic rejection at 72, 84, 177, and 396 days after transplantation. Death of the remaining animals was attributed to acute rejection (3 dogs); severe anemia (3 dogs); pulmonary infection and sepsis (3 dogs); and arterial thromboembolism (1 dog). In these long-functioning lung allografts, the alveolar lining cells were frequently replaced by very atypical cells presumed to be type 2 pneumocytes. The bronchus was occluded by mucus plugs, and the alveolar surface was covered with hyaline membrane, or obliterated by organized fibrocellular precipitate. The alveolar walls and perivascular area were thickened by fibrosis. Obliterative intimal thickening of pulmonary arteries was not observed. Although the immunologic and non-immunologic mechanisms responsible for the development of these lesions are difficult to separate, these cumulative changes apparently accompany the deterioration of the vital function of the graft until ultimate death.

Animals↗