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M Olausson

Publications and source records attributed to M Olausson.

142 records · Page 8Linked to original sources

Induction of long-term heart allograft survival in the rat by rabbit ATG.

A rat model for induction of transplantation tolerance, by antithymocyte globulin (ATG) as sole immunosuppressive agent, was studied. Vascularized heart allografts were employed. The conditions for establishment of long-term surviving (LTS) grafts were investigated as well as some of the characteristics of the tolerant state. The tolerance-inducing effect of ATG was found to be reproducible and dose-dependent. Treatment before grafting was essential. Preimmunization of the recipient inhibited the tolerance induction, while thymectomy seemed to have the opposite effect. The differences in survival of second allografts, third party or syngeneic to the first, indicated a largely strain-specific tolerance that most probably was the result of a changed host reactivity and for its induction strictly depended on presence of the graft. There were microscopical signs of rejection in the LTS grafts, while almost no such changes could be found in second allografts from the same donor strain, transplanted to the LTS-bearing recipients.

Animals↗

Suppressor cells in antithymocyte globulin-induced transplantation tolerance in the adult rat.

A rat heart allograft model, for induction of transplantation tolerance by a single dose of antithymocyte globulin, was studied. Experiments were made to transfer the tolerance to syngeneic recipients, either by spleen cells or sera obtained from tolerant rats. Different doses of tolerant spleen cells caused long-term surviving (LTS) allografts when transferred to sublethally irradiated recipients. Spleen cell transfer to untreated recipients resulted in prolonged allograft survival but no LTS grafts. The results indicate the presence of a cell-mediated suppressor mechanism in the tolerant animals.

Animals↗

Non-suture organ grafting to the neck vessels in rats.

Heterotopic organ transplantations in rats were performed either to abdominal vessels, using a conventional suture technique, or to neck vessels, using a non-suture cuff technique. The non-suture technique was found to be best suited for heart transplantation, but could also be employed for spleen and pancreas. In heart transplantation the non-suture model had the advantages of less preoperative bleeding, shorter operation and ischaemia times and easier monitoring of graft function than with the conventional technique. By combining the two techniques it was possible to transplant more than one vascularized graft to each recipient.

Abdomen↗

Fibrinopeptide A, beta-thromboglobulin, and fibrin degradation products as screening test for the diagnosis of deep vein thrombosis.

In a group of 111 consecutive patients (mean age 65 years) with suspected deep venous thrombosis (DVT) phlebography demonstrated DVT in 51. In all patients blood tests for fibrinopeptide A (FPA), fibrin degradation products (FDP) and beta-thromboglobulin (beta-Tg) were carried out. There was a significant difference in FPA concentration between the group of patients with a positive and a negative phlebography. However, there was a wide variation of individual values in both groups. The difference in FPA concentration between the groups was not related to differences in predisposing diseases, age or sex. FDP and beta-Tg did not differ between the groups and, again, a wide variation of individual values was found in both groups. In our hands, none of these three methods reflecting activities in the hemostasis seems to be useful to diagnose DVT in clinical routine work.

Adult↗

Singlet oxygen energy illumination during moderate cold ischemia prolongs the survival of concordant hamster xeno-heart transplants.

INTRODUCTION: Singlet oxygen energy (SOE) is a potent inhibitor of reactive oxygen species (ROS) in vitro and in vivo in certain dose ranges and can improve the levels of high-energy phosphates (HEP) in concordant hamster xeno-heart transplants. Some data indicate that a certain degree of cold ischemia (CI) might be beneficial to xenotransplants. We investigated if SOE illumination of hamster xeno-hearts during moderate cold ischemia (CI) improved graft survival. MATERIALS AND METHODS: Eighteen hearts from Golden Syrian hamsters (70 to 80 g) were subjected to 8 hours of CI in cold (+4 degrees C) saline solution (NaCL, 0.9%) before heterotopic cervical transplantation to Lewis rats (220 g). Among the treatment group (n = 8), SOE was produced by illuminating the hearts for 10 minutes every 30 minutes with photons at lambda 634 nm with the Oxylight equipment. Graft function was evaluated every 6 hours after transplantation with digital exam until cessation of heart beats. RESULTS: The graft survival of SOE-illuminated ischemic hamster xenografts was 2.34 +/- 0.56 versus 1.15 +/- 0.37 days in the control group (P < .05). All hearts displayed immediate graft function versus 70% in the controls (NS). CONCLUSIONS: SOE illumination at lambda 634 nm during moderate cold ischemia (+4 degrees C) can improve the survival of concordant hamster xeno-heart transplants. The exact mechanism(s) are currently unknown, but the effect might in part be exerted by a combination of reduced production of ROS and increased oxidative phosphorylation.

Animals↗

Accelerated acute rejection of the intestinal graft in CD28-deficient mice.

OBJECTIVE: Multiple in vivo studies have shown that the pace and severity of graft rejection is little or not at all changed by deleting CD28 molecules in the recipient. These findings contrast with the effects of monoclonal antibody therapy aimed the same costimulatory target. The objective of the present study was to evaluate how the acute rejection process is affected in CD28-deficient mice using a fully allogeneic, highly immunologically reactive transplant model. METHODS: Heterotopic vascularized small bowel transplants were performed in 24 recipient mice divided into 4 groups: 2 wild-type and 2 knockout groups. Each group consisted of 5 to 7 animals in which BalbC mice were used as intestinal donors to either wild-type C57BL6 or C57BL6 background CD28-deficient recipient mice. Selected endpoints were 3 and 6 postoperative days (POD). Intestinal rejection was evaluated by mucosal laser Doppler flowmetry (expressed in perfusion units) and histology (expressed in rejection grades). RESULTS: Acute rejection occurred in both wild-type and CD28-deficient groups. At POD 3, no significant difference was noted between groups in terms of mucosal perfusion and histology. At POD 6, significant differences in graft mucosal perfusion and histology revealed a more aggressive rejection in the CD28-deficient group compared to the wild-type group. CONCLUSIONS: The present study showed that the severity of intestinal graft rejection responses was amplified by deleting CD28 molecules. Together with data from other studies, these results suggest a different pattern of distribution and/or activation of CD28/B7 receptors in various organs.

Acute Disease↗

Laser-Doppler flowmetry in the monitoring of the human intestinal allograft: a preliminary report.

During acute rejection, graft endothelium becomes a prime target for recipient immune cells. Animal studies have shown reduced microvascular perfusion, probably due to increased endothelial-leukocyte interaction and endothelial impairment, leading to graft damage. Using laser-Doppler flowmetry (LDF), we correlated the microvascular blood flow in the intestinal mucosa of five patients receiving multivisceral grafts with clinical events and pathology results. Measurements (n = 75) were performed during the first 4 weeks posttransplantation by inserting the LDF flexible probe through the ileostomy for 25 to 30 cm. Forty-six of the 75 measurements were performed within 24 hours of endoscopy and biopsy. In uncomplicated cases, we recorded a gradual increase in mucosal perfusion during the first week posttransplantation that presumably reflected regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. Sudden and sustained decreases in mucosal perfusion by 30% or more compared to the previous measurements were associated with septic episodes, rejection, or both. LDF revealed a good sensitivity in monitoring the intestinal microcirculation. It was able to indicate perfusion changes associated with acute rejection. The relatively low specificity of LDF may be compensated by the low invasivity, allowing frequent investigation. LDF may be an additional tool for routine monitoring of intestinal allografts.

Adult↗

Transplantation of preconditioned intestinal grafts is associated with lower inflammatory activation and remote organ injury in rats.

Reperfused grafts--particularly the intestine--release free radicals and cytokines into the systemic circulation. The type of discharge, which is greatly dependent on the local injury, may also induce inflammatory activation in distant organs and leading to multiple system and organ failure. It has been suggested that intestinal grafts from tacrolimus (TRL)-pretreated donors show improved morphology and microcirculation. We studied whether transplantation of intestines from TRL-pretreated donors influenced inflammatory response and remote organ injury posttransplantation. Donor Sprague Dawley rats received TRL or saline (controls) intravenously at 6 hours prior to graft harvest. The intestinal grafts were preserved in saline for 3 hours before transplantation. At 6 and 12 hours postreperfusion hepatic and renal cortical microcirculation were assessed using laser-Doppler flowmetry (n = 8-12 per group). Blood pressure was measured; liver, kidney, and serum samples were obtained. We analyzed hepatic and renal ICAM-1 expression and caspase-3-like activity as well as plasma content of tumor necrosis factor-alpha and interleukin-6. Pretreated graft recipients had higher mean arterial pressure (82 +/- 10 vs 51 +/- 17 mm Hg, P < .05) and renal perfusion at 6 hours whereas liver perfusion was similar at both 6 and 12 hours. Liver and renal functions were also superior among recipients of pretreated grafts. Both caspase-3-like activity and ICAM-1 expression in liver and kidney were lower in pretreated graft recipients. Plasma IL-6 levels were lower in animals receiving pretreated grafts. Transplantation of intestines from TRL-pretreated donors was followed by a lower systemic inflammatory response, improved organ function and decreased remote injury early posttransplantation compared with animals receiving grafts from untreated donors.

Animals↗

Intestinal preservation injury: a comparison between different rat strains.

AIMS: Comparison between the extensive information on intestinal preservation injury in the rat is challenging since various preservation solutions, technical details, and grading systems have been used. This study investigates if strain represents another relevant variable for preservation injury outcome. METHODS: Grafts from Piebald-Viral-Glaxo (PVG), Lewis, Brown Norway (BN), Wistar, and Sprague-Dawley (SD) male rats (n = 8/strain) were used. Grafts were perfused and stored at 4 degrees C in University of Wisconsin (UW) solution (with or without luminal preservation). Intestinal histology was evaluated at 8, 16, and 24 hours of preservation using the Park score. Lactate, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and glucose were measured in the preservation solution. RESULTS: Grafts from PVG and Lewis showed significantly lower injury scores compared to BN, Wistar, and SD at 8 and 16 hours, a difference that disappeared at 24 hours of preservation. Luminal preservation significantly reduced the injury score for all strains, except SD, at 8 and at 16 hours, a difference that disappeared at 24 hours. Biochemical analyses of LDH and lactate levels show a similar pattern both between different strains and the effect of luminal preservation, although not statistically significant. CONCLUSION: Different rat strains seem to have different susceptibility to intestinal preservation injury under identical conditions. These results indicate that PVG and Lewis are more resistant to preservation injury than Wistar, BN, or SD. The beneficial effect of luminal preservation with UW solution is limited after 8 to 16 hours.

Adenosine↗