ABSTRACT
Procedures involving complex surgical techniques in rats, such as placement of abdominal aortic graft require extended duration of surgical anesthesia, which often can be achieved by repeated administrations of xylazine-ketamine combination. However such repeated anesthetic administration, in addition to being technically challenging, may be associated with potential adverse events due to cumulative effects of anesthesia. We report here the feasibility of using urethane at low dose (~1/10 the recommended anesthetic dose) in combination with a xylazine-ketamine mix to achieve an extended duration of surgical anesthesia in rats. The anesthesia induction phase was quick and smooth with an optimal phase of surgical anesthesia achieved for up to 90 minutes, which was significantly higher compared to that achieved with use of only xylazine-ketamine combination. The rectal temperature, heart rate and respiratory rate were within the physiological range with an uneventful recovery phase. Post surgery the rats were followed up to 3 months without any evidence of tumor or any other adverse effects related to the use of the urethane anesthetic combination. We conclude that low dose urethane can be effectively used in combination with xylazine and ketamine to achieve extended duration of surgical anesthesia up to 90 minutes in rats.
Subject(s)
Animals , Rats , Anesthesia , Heart Rate , Ketamine , Respiratory Rate , Transplants , Urethane , XylazineABSTRACT
OBJETIVO: Analisar as complicaçöes pós-operatórias dos transplantes microcirúrgicos alógenos de membro, bem como determinar fatores associados à toxicidade das drogas. MÉTODO. O estudo foi realizado entre combinaçöes de maior histocompatibilidade, utilizando 39 ratos Brown-Norway (doadores) e 78 ratos Fischer 344 (receptores), submetidos ao transplante microcirúrgico alógenode membro e ao tratamento imunossupressor com ciclosporina e RS-61443. RESULTADOS. Um (1/78: 1,28 por cento) foi sacrificado devido à trombose; dois (2/78:2,56 por cento) por enterite; um (1/78:1,28 por cento) devido à autofagia e oito (8/78:10,42 por cento) morreram por causa indeterminada. CONCLUSÄO. Dentre os 78 (78/78:100 por cento) ratos submetidos ao transplante alógeno microcirúrgico de membro, 12 (15,5 por cento) ratos morreram ou foram sacrificados devido às complicaçöes pós-operatórias agudas näo relacionadas à rejeiçäo, toxicidade dos agentes imunossupressores ou infecçäo oportunista
Subject(s)
Animals , Male , Rats , Mycophenolic Acid/analogs & derivatives , Cyclosporine/administration & dosage , Hindlimb/transplantation , Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/administration & dosage , Histocompatibility , Microsurgery , Postoperative Complications , Rats, Inbred BN , Transplantation, Autologous , Transplantation, Homologous/adverse effects , Transplantation, Homologous/mortalityABSTRACT
To study graft-versus-host disease (GVHD) in rat hindlimb allotransplantation, a model similar to intestinal transplantation was used. ACI and Lewis rats were crossed to produce F(1) generation rats (ACI-Lewis). These underwent limb transplantation receiving a donor limb from a Lewis rat. The animals were examined daily and skin biopsies were performed. Results showed that all limbs were viable at 34 weeks and no rats demonstrated any clinical evidence of GVHD and biopsies were grade 0.
Subject(s)
Animals , Rats , Graft vs Host Disease/epidemiology , Extremities/transplantation , Incidence , Rats, Inbred Strains , Rats, Inbred Lew , Skin/pathology , Transplantation, HomologousABSTRACT
The synergic effect of subtherapeutic doses of cyclosporine and RS-61443 was demonstrated in a vascularized rat hindlimb allotransplantation across a strong histocompatibility barrier (Brown-Norway as donors and Fischer 344 as recipients). Low doses of agents in combination minimized the toxicity while increasing the therapeutic efficacy. All animals showed weight loss during the first 15 days posttransplantation and they regained protective sensation within 45 postoperative days. Only 15.38 per cent of the animals presented complications: thrombosis, enteritis, autophagia and disorders of unknown etiology.
Subject(s)
Animals , Rats , Mycophenolic Acid/therapeutic use , Cyclosporine/therapeutic use , Drug Therapy, Combination , Extremities/transplantation , Immunosuppressive Agents/therapeutic use , Graft Rejection/prevention & control , Enteritis/etiology , Postoperative Complications , Rats, Inbred BN , Skin/pathology , Thrombosis/etiology , Transplantation, Homologous/immunologyABSTRACT
Os transportes alógenos de tecido composto contribuiram sobremaneira para reparaçäo das deformidades congênitas, traumáticas e tumorais. OBJETIVO. Prevenir ou inibir o processo de rejeiçäo em transplante microcirúrgico alógeno de membro; diminuir a toxicidade das drogas imunossupressoras; verificar um melhor efeito imunossupressor através da possibilidade do efeito sinérgico da associaçäo de doses subterapêuticas de ciclosporina e RS-61443. MÉTODOS. Cinco grupos foram estudados, usando Brown-Norway, doadores e Fischer 244, receptores: grupo A, controle autógeno sem tratamento; grupo B, alógeno, sem tratamento; grupo C, alógeno + ciclosporina 1,5mg/Kg/d sc; grupo D; alógeno + RS-61443 15mg/Kg/d; e grupo E, alógeno + CsA + RS. RESULTADOS. De acordo com o processo de rejeiçäo, os resultados foram o seguinte: grupo A, nenhum animal apresentou rejeiçäo (0 por cento). Todas as biópsias resultaram em grau 0; grupo B, todos desenvolveram rejeiçäo entre o 10º e o 13º dia pós-operatório. As biópsias cutâneas confirmaram a necrose epidérmicas (grau 4); grupo C, 55 por cento desenvolveram rejeiçäo; grupo D, 94 por cento apresentaram rejeiçäo e em contraste; no grupo E, 94 por cento dos animais sobreviveram livres do processo de rejeiçäo, por mais de 172 dias de transplante. CONCLUSäO. A associaçäo de duas drogas imunossupressoras (ciclosporina + rs-61443), em doses subterapêuticas, foi eficiente em prevenir o processo de rejeiçäo e apresentou um melhor efeito imunossupressor pelo efeito sinérgico da associaçäo destas drogas