title: Total lymphoid irradiation and discordant cardiac xenografts.
abstract: Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.
authors.affiliation: Department of Surgery, Tufts University School of Medicine, Boston, MA.
authors.forename: E
authors.initials: E
authors.lastname: Kaplan
authors.forename: A R
authors.initials: AR
authors.lastname: Dresdale
authors.forename: J T
authors.initials: JT
authors.lastname: Diehl
authors.forename: N A
authors.initials: NA
authors.lastname: Katzen
authors.forename: M J
authors.initials: MJ
authors.lastname: Aronovitz
authors.forename: M A
authors.initials: MA
authors.lastname: Konstam
authors.forename: D D
authors.initials: DD
authors.lastname: Payne
authors.forename: R J
authors.initials: RJ
authors.lastname: Cleveland
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D006084:Graft Rejection / Q000528:radiation effects*; D006085:Graft Survival / Q000528:radiation effects; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015182:Lymphatic Irradiation; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents