PubMed Health⌕ Search

Biomedical subjects

G H MacKenzie

Publications and source records attributed to G H MacKenzie.

At least 19 recordsLinked to original sources
PubMed1985

Influence of oxygen-derived free radical scavengers on ischemic livers.

It has been hypothesized that the formation of oxygen-derived free radicals may play an important part in ischemically induced tissue injury. Using a canine ischemic liver model, we have assessed the role of two oxygen-free radical scavengers, catalase (CAT) and superoxide dismutase (SOD), used alone and in combination, on the recovery of ischemic livers. Liver ischemia was induced in adult mongrel dogs by cross-clamping of the portal vein and hepatic artery for 40 min. Hepatectomy was then performed, and livers were tested in an isolated perfusion model with 500 ml of an albumin-mannitol solution at 37 degrees C for 3 hr. Liver function tests were performed hourly during the perfusion period. Biopsies and 99m-Tc-HIDA scans were also done at the end of perfusion. Livers in group 1 (n = 6) served as controls and were not pretreated prior to ischemic injury. Livers in group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6) were pretreated, respectively, with CAT (5000 U/kg), SOD (5000 U/kg), and SOD and CAT in combination (5000 U/kg) each. The results indicated that the oxygen-derived free radical scavengers, CAT and SOD, were able to provide partial protection against the free radicals accumulated during ischemic damage. These studies offer some potential avenues for the protection of livers prior to and after transplantation.

Alkaline Phosphatase↗
PubMed1985

Renal subcapsular islet cell transplantation.

This study was directed towards improving islet cell allotransplantation (ICTx) by testing the renal subcapsular region (RSC) as an alternative site for graft placement. In addition, a simplified, non-collagenase method was assessed for preparation of the allograft from the donor pancreas. Five groups of pancreatectomized mongrel dogs were followed. Group I (n = 10) were not transplanted and survived 5.0 +/- 2.92 days (M +/- SD). Five of six animals in Group II (n = 6) which received an ICTx prepared without collagenase in the RSC survived until allograft removal by nephrectomy at greater than 90 days (P less than .0005). No immunosuppression was given to this group. Recipients in Group III (n = 11) were transplanted as in Group II, but were given minimal immunosuppression with azathioprine. They also demonstrated excellent graft function until removal of the graft by nephrectomy at between 3 weeks and greater than 90 days. Animals in Group IV (n = 6) received an intrasplenic (IS) ICTx prepared without collagenase and survived only 4.16 +/- 1.16 days. In Group V (n = 6) poor survival was also noted (7.66 +/- 4.58 days) after IS-ICTx of a collagenase prepared allograft. All animals in Group IV and V received minimal immunosuppression as in Group III. These results indicate the potential for utilization of the RSC as an alternative site for ICTx. In addition, the collagenase-free method was satisfactory for ICTx preparation.

Animals↗
PubMed1984

Renal subcapsular islet cell transplantation.

Islet cell transplantation has been associated with ultimate graft rejection. This preliminary study investigates the use of the renal subcapsular region as a site for placement of canine islet cell allografts. A new noncollagenase mechanical technique was used for preparation of the allografts. Animals in group I (N = 6) died of hyperglycemia in 4.0 +/- 1.89 days (X +/- SD) after pancreatectomy without subsequent islet cell transplant. Normoglycemia and excellent survival (greater than 60 days) was obtained in pancreatectomized animals in group II (N = 6) and in group III (N = 6), who received an islet cell allograft to the renal subcapsular site. Group II recipients were given no immunosuppression, and animals in group III received minimal immunosuppression with azathioprine. Dependence on the islet cell allograft for maintenance of normoglycemia was confirmed in the majority of the recipients by nephrectomy, to remove the graft, with resulting hyperglycemia and death. One normoglycemic animal in group II died on day 6 from peritonitis. One recipient in group II was normoglycemic at greater than 1 mo after removal of the first graft by nephrectomy, followed by retransplantation of islet cells from a third-party donor. Two other recipients are being studied on a long-term basis, and have been normoglycemic for greater than 6 mo and greater than 4 mo after transplantation. These studies encourage further investigation in this area for application of islet cell transplantation in man, and elucidation of the possible mechanisms for prolongation of islet cell allograft survival at the renal subcapsular site.

Animals↗
PubMed1984

New avenues in the use of cyclosporine for transplantation. Graft and donor pretreatment.

Modification of graft immunogenicity using graft (GPTX) and donor pretreatment (DPTX) has been pursued in an attempt to modify allograft immunogenicity using various immunosuppressive agents. The murine skin allograft and canine renal allograft models were used to study the efficacy of Cyclosporine (Cy A) as a DPTX and GPTX prior to transplantation. Tail skin allografts from C3HHeN male mice were grafted to Balb/c female mouse recipients. Minimal immunosuppression was given to all skin graft recipients. Skin allograft were either GPTX with Cy A, DPTX with either Cy A, methylprednisolone (MP), or cyclophosphamide (CP), or Cy A GPTX and DPTX with the three drugs alone or in combination. Cy A GPTX alone of skin allografts did not significantly prolong survival. DPTX with Cy A significantly prolonged skin graft survival, however, CP or MP alone did not. The various combinations of MP, Cy A, and CP as DPTX and MP, Cy A, and CP DPTX used together with Cy A GPTX also significantly prolonged murine skin allograft survival. Kidney allografts used unrelated mongrel dogs as donors or recipients. Renal transplant experimental groups were either: Non-pretreated and immediately transplanted, nonpretreated and hypothermically stored (HS) for 24 hours in Collins (C-2) solution, GPTX with 12.5 mg Cy A during 24 hr. HS in C-2, DPTX with Cy A (25 mg/Kg), or Cy A DPTX (15 mg/kg) and GPTX during 24 hrs. HS in C-2. Cy A GPTX during HS was sometimes effective in prolonging kidney allograft survival greater than 30 days using only minimal immunosuppression with azathioprine. Cy A DPTX prolonged survival somewhat, but not significantly. Improved results were seen, however, when Cy A DPTX was used together with Cy A graft pretreatment. These results indicate the potential for the successful use of Cy A as a donor and/or graft pretreatment, however, further studies will be necessary to optimize the use of Cy A in these modalities.

Animals↗
PubMed1984

Orthotopic liver transplantation. Various immunosuppressive regimens to improve survival.

New approaches to immunosuppression, including cyclosporin A (Cy A), are being utilized to improve liver transplantation survival results. Donor livers from unrelated dogs were orthotopically transplanted to recipient animals, and only recipients that survived 2 or more days were included in this study. Animals were divided into the following groups: Group 1 (n = 6) received minimal immunosuppression (azathioprine) after orthotopic liver transplantation, Group 2 (n = 7) liver allografts were pretreated with Cy A (50 mg/L) prior to transplantation, and recipients were given minimal immunosuppression as in Group 1, Group 3 (n = 6) animals received azathioprine and methylprednisolone after transplantation, and Group 4 (n = 6) liver allograft recipients were given Cy A and methylprednisolone for 30 days followed by azathioprine. The improved survival seen in Groups 2, 3, and 4 in comparison with Group 1 (minimally immunosuppressed controls) indicates that graft pretreatment with Cy A or prophylactic Cy A administration (30 days), in conjunction with minimal immunosuppression, can prolong canine liver allograft survival as well as more standard regimens (Group 3). Therefore, it is possible that the use of steroids could be reduced or eliminated in hepatic transplantation with the application Cy A.

Animals↗
PubMed1984

Transplantation of islet cells.

In an effort to improve the viability of canine pancreatic islet cell allografts after cryopreservation, Cy A was used for graft pretreatment and as a general immunosuppressant on graft recipients who had previously undergone pancreatectomy. Using this combination in conjunction with cryopreservation, islet cell allografts exhibited good viability and long term function after freezing to minus 196 degrees C. These results might encourage the further use of this technique for transplantation.

Animals↗
PubMed1983

Immunosuppression with cyclosporine. A new approach to improve patency of venous allografts.

In cases in which an autogenous vein is not available, the venous allograft still represents an interesting alternative; however, early occlusion of the allograft is the rule. Forty-five mongrel dogs received jugular allografts transplanted into the carotid artery. Group 1 (n = 6) received no immunosuppression; group 2 (n = 5) received systemic azathioprine (2.5 mg/kg/day). In group 3 (n = 10) the grafts were pretreated with cyclosporine at 4 degrees C, and in group 4 (n = 9) the grafts were cryopreserved in a solution of 15% dimethyl sulfoxide and cyclosporine (50 mg/L) at -196 degrees C prior to implantation. Groups 3 and 4 received azathioprine as in group 2. Group 5 received cyclosporine systemically (15 to 20 mg/kg/day). Patency rates at one month (groups 1 and 2, 0%; group 3, 57.1%; groups 4 and 5, 100%) indicate that cyclosporine improves venous allograft survival both when used systemically and as a graft pretreatment modality.

Animals↗
PubMed1983

Application of cryopreservation techniques to islet cell allotransplantation.

This study continues our investigations in the area of canine islet cell cryopreservation. Islet cell allografts were frozen using a simple method to -196 degrees C with rapid freezing rates and dimethyl sulfoxide as the cryoprotectant. Good in vitro viability was observed using trypan blue dye exclusion. After intrasplenic transplantation, grafts which did not reject were able to maintain normoglycemia for periods of greater than 60 days. The use of either Cy A as an immunosuppressant or ALG as a graft pretreatment contributed to prolongation of allograft survival in these long-term surviving recipients. These results encourage further studies in this area for potential future clinical application of this technique to human pancreas.

Animals↗
PubMed1983

Graft pretreatment with cyclosporin A. Long-term study including four trials in one and a half years.

Four trials were conducted to establish whether Cyclosporin A (Cy A) could be used as a graft pretreatment to prolong the graft function and animal survival of kidneys transplanted into bilaterally nephrectomized mongrel dogs. The first nonrandomized trial analyzed various parameters such as concentration, flush temperatures, effect of reflushing, and the need for subsequent minimal immunosuppression. By analyzing data from the ten groups in this trial, we established that 50 mg/l Cy A could be flushed successfully at either 4 C or 25 C without nephrotoxic effects. This concentration was found to prolong graft function and animal survival in some animals greater than 100 days. Reflushing the kidney after primary graft pretreatment with Cy A did not entirely remove the immunosuppressive effect of the drug as significant prolongation of survival also was observed in this group. In addition, minimal immunosuppression with azathioprine was necessary to observe a delay in the onset of rejection and prolongation of animal survival when Cy A was used for graft pretreatment. Trials 2 and 4 compared the efficacy of the original batch that was obtained later. The effects observed in Trial 1 and reproduced in Trial 3, which were randomized and double blinded using the original batch, were not seen in either Trials 2 or 4. This may have been related to the amount of time that the Cy A was dissolved in ethanol prior to its use or the batch of Cy A utilized. These preliminary results indicate that Cy A, when used for graft pretreatment under certain conditions, can delay the onset of rejection and prolong animal survival of transplanted renal allograft recipients.

Animals↗
PubMed1982

Prolongation of pancreatic islet cell allograft survival by graft pretreatment with antilymphoblast globulin (ALG).

The effect of antilymphoblast globulin (ALG) as a graft pretreatment for pancreatic islet cell allografts was tested in the canine model. Previous experiences on minimally immunosuppressed renal allografts had demonstrated significant prolongation of survival after graft pretreatment with ALG. ALG was injected with pancreatic islet cell fragment allografts that had been processed by mincing and subsequent collagenase digestion into the splenic pulp after total pancreatectomy of recipients immunosuppressed only with azathioprine following transplantation. Graft survival for pancreatic controls was 5.6 +/- 2.59 (M +/- SD) days. Islet cell allografts that received no ALG had a mean survival of 11.0 +/- 13.99 days (M +/- SD), P greater than 0.1). However, allografts pretreated with ALG had a significantly longer graft survival of 29.6 +/- 18.7 days (M +/- SD,P less than .01). Therefore, the spleen not only is an acceptable site for pancreatic islet cell transplantation in the dog, but significant graft prolongation can be achieved by utilization of ALG as a graft pretreatment modality for recipients receiving minimal immunosuppression with azathioprine.

Animals↗
PubMed1982

Immunologic response to liver cell allografts.

Hepatocyte transplantation is one modality that has been suggested for providing temporary hepatic support during periods of liver regeneration following acute hepatic failure. Although liver cells have been successfully transplanted in the rat, transplantation in a larger model is necessary before these techniques can be applied clinically. This study attempts to define the immunologic response of the canine recipients to intrasplenic hepatocyte allografts. Our results indicate that canine hepatocytes are highly immunogenic, initiating a host response which destroyed the allograft within one week post-transplantation (survival range 1-6 days, mean +/- SD = 3.33 +/- 1.86 days). Administration of azathioprine post-transplantation significantly (P less than 0.01) extended the survival of the hepatocyte allografts (survival range 3-9 days, mean +/- SD = 5.66 +/- 2.16 days. However, long-term survival was not seen using this type of minimal immunosuppression. Histologic observation also confirmed these findings. Based on these results, therefore, caution is recommended prior to the application of hepatocyte transplantation to the clinical setting.

Animals↗