Selective lymphoid irradiation and cyclosporin A in rat heart allografts
Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.
- Research Organization:
- Columbia Coll. of Physicians and Surgeons, New York, NY
- OSTI ID:
- 6347689
- Journal Information:
- J. Surg. Res.; (United States), Vol. 36:5
- Country of Publication:
- United States
- Language:
- English
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ANTIBIOTICS
SYNERGISM
IMMUNOSUPPRESSION
RADIOINDUCTION
LYMPHATIC SYSTEM
BIOLOGICAL RADIATION EFFECTS
PARTIAL BODY IRRADIATION
DOSE-RESPONSE RELATIONSHIPS
HEART
HEMATOPORPHYRINS
IMMUNE REACTIONS
PALLADIUM 109
RATS
SURVIVAL TIME
TRANSPLANTS
ANIMALS
ANTI-INFECTIVE AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
DRUGS
EVEN-ODD NUCLEI
EXTERNAL IRRADIATION
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IRRADIATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PALLADIUM ISOTOPES
PIGMENTS
PORPHYRINS
RADIATION EFFECTS
RADIOISOTOPES
RODENTS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals