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Biomedical subjects

A G Rose

Publications and source records attributed to A G Rose.

At least 145 records · Page 8Linked to original sources
PubMed1975

The autopsy findings in a case of heterotopic cardiac transplantation with left ventricular bypass for ischaemic heart failure.

The autopsy findings in a White man aged 59 years are presented; he underwent heterotopic cardiac transplantation with left ventricular bypass for irreversible left ventricular failure caused by severe ischaemic heart disease. Microscopically, the donor heart showed mild signs of chronic rejection with negligible loss of functional myocardium, and no complications attributable to the surgical technique. Severe, generalised atherosclerosis had resulted in fibrous replacement of the recipient left ventricular myocardium and intra-operative atheromatous embolisation to the brain, the latter being the main contributory factor in the patient's death. Other significant findings were bilateral femoral vein thrombosis with recurrent pulmonary infarction, Aspergillus granulomata of the right lung, cytomegalovirus infection of lungs and oesophagus, Herpes simplex infection of the tongue and oesophagus, and duodenal ulceration with haemorrhage.

Arteriosclerosis↗
PubMed1972

Disseminated Herpesvirus hominis (herpes simplex) infection: retrospective diagnosis by light and electron microscopy of paraffin wax-embedded tissues.

Disseminated Herpesvirus hominis infection had previously been reported from other parts of the world, but the disease was initially recognized at necropsy in Cape Town in 1957 (McKenzie, Hansen, and Becker, 1959).The present retrospective study established that the disease had been occurring before 1957 but that its aetiology had not been recognized. An awareness of the disease, together with an adequate knowledge of the clinical history, the morbid anatomy, and histology of the lesions, usually allows a confident diagnosis to be made.

Autopsy↗
PubMedDate not supplied

Histopathology of hyperacute rejection of the heart: experimental and clinical observations in allografts and xenografts.

The histologic findings in a total of 112 experimental heart transplants comprising allografts (baboon to baboon: n = 37), concordant xenografts (vervet monkey to baboon: n = 52), and discordant xenografts (pig to baboon: n = 23), in which the roles of ABO blood group incompatibility, corcordance, and immunosuppression were evaluated, are described. Hyperacute (vascular, humoral) rejection was characterized by disruption of the microcirculation, with interstitial hemorrhage and edema, rather than by intravascular thrombosis; the features were basically similar whether hyperacute rejection occurred in an ABO-incompatible allograft, concordant xenograft, or discordant xenograft. Hyperacute rejection was noted in all 23 discordant xenografts, in 12 to 52 concordant xenografts, and in four of 17 ABO-incompatible allografts. A unique mixture of acute and hyperacute rejection was observed in three ABO-incompatible allografts and in 10 concordant xenografts. Intensive antirejection therapy was associated with a reduced incidence of hyperacute rejection in corcordant xenografts but also with a significant number of fatal treatment-related complications.

ABO Blood-Group System↗
PubMedDate not supplied

Optimalization of immunosuppression after xenogeneic heart transplantation in primates.

Xenogeneic heart transplantation is becoming increasingly attractive because of the shortage of suitable donor organs. In small infants and neonates, for whom suitable human grafts are difficult to obtain, this may play a particularly important role. To evaluate the optimal immunosuppressive regimen after xenogeneic transplantation, cervical heterotopic heart transplantation was performed with vervet monkeys as donors and chacma baboons as recipients. The following groups were investigated: group 1 (n = 9): control, no immunosuppressive medication; group 2 (n = 5): cyclosporine in combination with azathioprine and methylprednisolone; group 3 (n = 6): cyclosporine, azathioprine, and methylprednisolone in combination with antithymocyte globulin for postoperative days 0 to 9; group 4 (n = 7): cyclosporine, azathioprine, and methylprednisolone in combination with 15-deoxyspergualin for postoperative days 0 to 9. Because of severe treatment-related side effects that were observed in group 4, further immunosuppression was modified as follows: group 5 (n = 5): 15-deoxyspergualin was combined with cyclosporine and methylprednisolone only. Acute rejection episodes were diagnosed by cytoimmunologic monitoring on alternate days and weekly myocardial biopsies and were treated with 500 mg methylprednisolone intravenously for 3 to 5 consecutive days. The graft survival after xenogeneic heart transplantation was best in group 3 with 43.3 days compared with 10.3 days in the control group. Still 2.3 acute rejections occurred, which in most cases led to graft failure in these animals. In group 4 the graft survival was prolonged to 20.1 days on average. Only 0.5 acute rejections per animal occurred, but severe gastrointestinal complications and infections were observed that made further experiments necessary to minimize these treatment-related complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Acute pulmonary rejection precedes cardiac rejection following heart-lung transplantation in a primate model.

Twelve Chacma baboons underwent transplantation of the heart and both lungs from donor baboons matched for size and AB blood group. Cyclosporine was given daily orally, by twice daily intravenous injections, or by a single intravenous injection (together with oral azathioprine and, after 2 weeks, methylprednisolone); whole blood trough levels were inadequate in all groups. Survival was from 4 to 29 days, with death resulting from acute rejection of the lungs in 11 and from bronchopneumonia in one. In the 11 animals dying from rejection, histologic examination showed that the heart was spared from severe rejection in all cases but one. In the inadequately immunosuppressed baboon, therefore, acute rejection occurs earlier in the lungs than in the heart. We have now observed what we believe to have been acute pulmonary rejection in the absence of cardiac rejection on five occasions in three patients in our clinical transplantation program. We would suggest that pulmonary rejection must always be strongly suspected if there are any suggestive features, particularly pulmonary shadowing on chest radiographs, despite negative results of tests indicating rejection of the heart. In the absence of any easy method of confirming pulmonary rejection directly (other than open-lung biopsy, which is clearly contraindicated as a routine procedure), we suggest that more attention should be directed toward developing tests for rejection that are not organ specific, rather than relying on techniques that diagnose cardiac rejection only.

Animals↗
PubMedDate not supplied

Successful orthotopic heart-lung transplantation in the baboon after five hours of cold ischemia with cardioplegia and Collins' solution.

En bloc transplantation of the heart and lungs was performed in 15 chacma baboons; the donor organs were stored between 4 and 6 hours before transplantation. The hearts were perfused in the donor animals with 15 ml/kg Wicomb's cardioplegic solution at 4 degrees C, the lungs with either 20 ml/kg 4 degrees C Collins' solution with an added 2.5% dextrose and 12 mEq magnesium sulfate (Collins' solution, group 1, n = 8), Collins' solution plus superoxide dismutase (40,000 U/L superoxide dismutase, group 2, n = 4), or Collins' solution plus superoxide dismutase plus peroxidase (5000 U/L peroxidase plus mannitol, group 3, n = 3). The pulmonary artery perfusion pressure was not allowed to exceed 50 cm water; the lungs were maintained at 30% to 50% inflation, and external cooling was applied. After explantation the thoracic organs were stored in 0.9% saline solution at 4 degrees C. In groups 1 (Collins' solution) and 2 (Collins' plus superoxide dismutase) all surviving baboons revealed normal blood gas values and normal light and electron microscopic histology at 24 hours. Three animals had further biopsies at intervals between 1 and 9 days, at which time the histology of the lungs proved normal and well preserved. All three baboons in group 3 (Collins' plus superoxide dismutase plus peroxidase) had grossly abnormal blood gas values from the time of operation, and all died within 9 hours; light microscopy of the lungs showed early lung infarctlike lesions and in one case pulmonary edema. These preclinical findings proved that storage of the lungs in Collins' solution with or without superoxide dismutase is possible for up to 5 hours; the addition of peroxidase had a detrimental effect.

Animals↗
PubMedDate not supplied

Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon.

The problem of donor heart supply would be solved if hearts could be transplanted from readily available animals such as the pig or sheep. We have investigated heterotopic heart transplantation (in the neck) with the pig as donor and baboon as recipient. Five experimental groups were studied. Control hearts (group 1, n = 4) were rejected within 4 minutes to 8 hours. Splenectomy done before transplantation (group 2, n = 3) did not extend survival significantly (30 minutes to 8 hours). Donor heart survival in baboons receiving immunosuppressive therapy of cyclosporine and methylprednisolone (group 3, n = 5) was from 15 to 75 minutes only in four animals and for 5 days in one animal. Anti-pig antibody adsorption from baboon blood by pretransplant donor-specific kidney hemoperfusion (group 4, n = 7) resulted in cardiac function for 6 to 12 hours in three cases and from 4 to 5 days in four cases (p less than 0.02). A combination of pretransplant antibody adsorption and immunosuppression (group 5, n = 4) resulted in graft survival of 8 to 20 hours in three cases and of 4 days in one case (p less than 0.03). Histopathologic features of vascular (hyperacute) rejection were seen in all hearts except one (the 5-day survivor in group 3). Pretransplant adsorption of antibody clearly prolonged survival of discordant cardiac xenografts in some cases. Further exploration of this technique appears justified.

Adsorption↗
PubMedDate not supplied

Hemodynamic and myocardial histologic and ultrastructural studies on baboons from 3 to 27 months following autotransplantation of hearts stored by hypothermic perfusion for 24 or 48 hours.

Hemodynamic and myocardial histologic studies have been made in four baboons, each of whom had undergone heart excision and storage, followed by autotransplantation. The excised baboon heart was stored by continuous hypothermic perfusion for 24 or 48 hours and then replaced orthotopically, the baboon being maintained alive in the interim by an orthotopic cardiac allograft. Follow-up of the autotransplanted baboons has been from 3 to 27 months. Cardiac catheterization revealed normal function both early and late after the period of storage. In three animals, myocardial histology was normal on light microscopy, although some dilation of the T tubules was seen on electron microscopy. In the fourth baboon, whose heart had been stored for 48 hours with follow-up for 13 months, light microscopy revealed some variation of staining of the myofibers and mild interstitial edema; ultrastructural studies showed mild intracellular edema, focal scanty loss of myofilaments, and a lack of dilation of the T tubular system. With this one possible exception, this study confirms that the system of hypothermic perfusion storage developed in our laboratory does not have any significant damaging effects on myocardial function or structure. There would appear, therefore, to be no contraindication to its use in clinical heart transplantation.

Animals↗
PubMedDate not supplied

Hyperacute rejection in a discordant (pig to baboon) cardiac xenograft model.

Eight freshly excised pig hearts were hemoperfused by baboons in vivo. Cardiac function ceased in six hearts after a mean period of 90 minutes of perfusion (range 30 to 190 minutes). Two hearts continued functioning for the 4-hour study period. On microscopic examination, seven hearts, including one that continued beating, showed histopathologic features of hyperacute rejection. IgG, IgM, and C3 were strongly present on the myocardium in all cases. Hemoperfusion was associated with significant increases in heart mass (p less than 0.002) and circulating polymorphonuclear leukocytes (p less than 0.03) and reductions in coronary blood flow (p less than 0.0001), circulating lymphocytes (p less than 0.03), and C4 (p less than 0.03). Preformed circulating anti-pig antibodies disappeared in all but one baboon. Hyperacute rejection in this discordant xenograft model that used a nonhuman primate as "recipient" differs in few aspects from that seen in other experimental models. Possible methods of prolonging xenograft survival are discussed.

Animals↗