Experimental model for graft -versus-host disease in rat limb allotransplantation

A Síndrome Enxerto versus Hospedeiro (SEVH) é uma condição imune potencialmente fatal que ocorre quando linfócitos transplantados do órgão doador reconhecem como estranho o tecido do receptor e tenta destruí-lo. Este modelo tem como objetivo verificar a incidência de SEVH em transplantes alógenos de membro. Duas espécies, ratos ACI e Lewis, lócus de maior e menor histocompatibilidade, foram combinadas. Determinar a incidência da SEVH nos transplantes alógenos de membro; estudar a regeneração nervosa e a toxicidade das drogas imunosupressoras; determinar a prevenção e o tratamento desta síndrome.

Small bowel transplantation and chronic rejection alter rat intestinal smooth muscle structure and function.

BACKGROUND: The purpose of this study was to determine whether morphologic and functional changes in intestinal smooth muscle occur after small bowel transplantation (SBTx) and during chronic rejection. METHODS: Orthotopic SBTx was performed in syngeneic (ACI-ACI, n = 6) and allogeneic (ACI-Lewis, n = 6) rat strain combinations. The latter received temporary immunosuppression (cyclosporine 15 mg/kg/body weight on postoperative days 0 to 6 once a day, postoperative days 7 to 28 every other day), which led to clinically quiescent chronic rejection of the graft by 90 days after SBTx. At that time structure and function of the jejunal muscularis externa were evaluated with histochemistry, mechanical organ bath, and intracellular electrical recording techniques. RESULTS: Histochemistry showed a 1.5-fold thickening of the intestinal muscularis externa of syngeneic grafts, although contractile properties and intracellular electrical activity were not significantly different from controls. Allogeneic, chronically rejecting grafts showed a threefold increase in the thickness of the muscularis externa as a result of both smooth muscle hyperplasia and hypertrophy. Muscle strips from chronically rejecting grafts generated only 23% of the maximal contractile force generated by controls (bethanechol 300 mumol/L). Median effective concentration and threshold values were not significantly different. Intracellular electrical activity of circular smooth muscle cells revealed a significantly more depolarized resting membrane potential and a reduction in slow wave amplitude compared with controls. CONCLUSIONS: Syngeneic SBTx resulted in a significant thickening of the muscularis externa with an apparent adaptation to control in vitro physiologic function. Allogeneic SBTx subject to chronic rejection leads to profound morphologic changes and functional impairments. Changes in muscle structure and function evolve before the clinical signs of graft rejection.

The use of cryopreserved venous allografts in microvascular surgery without immunosuppression: an experimental study.

Excellent patency rates are currently established in the use of autogenous veins as interposition vein grafts in microsurgical practice. Allografts may be a viable alternative source of vein grafts. Recent advances in cryobiology have enabled the controlled freezing of tissues with preservation of vital cellular elements. Although several reports have shown the successful use of cryopreserved large-vessel allografts, few have addressed cryopreservation of microvessels (1 to 2 mm in diameter). In this study, the authors have successfully cryopreserved femoral veins in a rat model and transplanted them as interposition vein grafts into arterial defects across major histocompatibility barriers (ACI to Lewis). Short-term patencies (21 days) were determined, and histologic and scanning electron microscopic analysis were performed. Patency of 100 percent was achieved in both fresh control veins and in cryopreserved veins at 21 days.

FK 506 reverses acute graft-versus-host disease after allogeneic bone marrow transplantation in rats.

Severe graft-versus-host disease was induced by transplantation of ACI rat bone marrow and spleen cells into irradiated Lewis rat recipients. Treatment with FK 506 or cyclosporine A (CsA) was started after clinical and histologic evidence of acute GVHD was present. A 14-day course of FK 506 at 1.0 mg/kg/day could rescue 100% of the animals suffering from GVHD. In contrast only one half of the animals treated with CsA at a high dose of 25 mg/kg/day recovered. After cessation of immunosuppressive therapy, FK 506-treated animals displayed a marked prolonged disease-free interval as compared to CsA-treated bone marrow recipients. Recurrence of the disease in these animals could be prevented when FK 506 treatment was continued after the induction period with a low maintenance dose of 0.1 mg/kg/day every other day.

Polymorphism of cyclic 3',5'-adenosine monophosphate stimulation in rat erythrocytes.

Significant differences were found in the cyclic 3',5'-adenosine monophosphate (cAMP) levels in (-)-isoproterenol-stimulated rat erythrocytes. The BN strain had the highest level (13.1 +/- 1.29 pmol cAMP/10 mg Hb) and the LEW strain had the lowest cAMP level (3.29 +/- 1.76 pmol cAMP/10 mg Hb) in the erythrocytes. The high levels were inherited in three intercrosses in a dominant fashion. The results of the backcross breeding suggested diallelic inheritance. However, the polygenic effect was not ruled out.