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Study Demonstrates Synergistic Effects of Drugs in
Facilitating Transplants

A recent study by researchers at Goteborg University in Goteborg, Sweden, demonstrates that two common immunosuppressive drugs used in transplant surgery actually work much better in combination than separately. The researchers led by Dr. Michael Olausson of the Department of Transplantation and Liver Surgery showed that two common transplant drugs that have been used separately but never before in combination have major synergistic effects that make it possible to reduce the dosage of each which should lower side effects. The effects of the drugs were studied by grafting heart tissue to the necks of laboratory rats and measuring how long the graft tissue survived. The use of Origin, a technical graphics software, helps to produce charts that quickly and clearly communicate the results of the charts to those who may be able to use them to reduce the side effects experienced by transplant patients.


Group Treatment N Mean Median SD LTS(%) pvalue
I. Untreated 23 8,3 8,0 1,8 0 -
II. Linomide ® 9 8,7 9,0 1.0 0 -
III. Cya 10mg/kg 15 83,5 100,0 34,4 80,0 III vs IV p<0,001
IV. Cya 10mg/kg+Linomide ® 14 8,0 8,0 1,9 0 -
V. ATG 0,02ml 34 32,8 11,5 38,2 23,5 -
VI. ATG 0,02ml+Linomide ® 17 10,3 10,0 4,1 0 V vs VI p<0,001
VII. ATG 0,1ml 24 75,2 100,0 39,7 70,8 -
VIII. ATG 0,1ml+Linomide ® 16 77,1 100,0 41,1 75,0 -
IX. ATG 0,2ml 22 95,8 100,0 19,6 95,5 -
X. ATG 0,2ml+Linomide ® 23 36,3 16,0 36,6 21,7 IX vs X p<0,01
XI. ATG 0,02ml+Linomide ® +Cya 10mg/kg 11 28,6 13,0 35,3 18,2 XI vs IV and VI p<0,001

Table 1. Graft survival Table 1. Graftsurvival in days and proportion of rats with long term surviving (LTS) grafts in groups I-XI.


The drugs used to suppress rejection of the transplanted organ typically have serious side effects so surgeons strive to provide as low a dose as possible. This can best be achieved in a multiple immunosuppressive drug protocol. Many surgeons today prescribe a triple drug regimen that includes Azathioprine (Aza), Prednisolone and Cyclosporine A (CyA). Protocols using antithymocyte globulin (ATG) have also been used in sequential therapy regimens in kidney transplant patients for several years as well as a treatment for graft rejection episodes. Yet, no one has ever looked for synergistic effects between ATG and CyA, despite the wide use of both drugs, partly because of the difficulty of distinguishing between the effects of two such powerful drugs. Fortunately, a recent report showed that LS2616 (Linomide) can completely inhibit the immunosuppressive effects of CyA. This makes it possible to study the possible synergistic effects of ATG and CyA in a standardized manner.

Male inbred rats, weighing 200-220 grams, were used as recipients and female rats, weighing 70-130 g as donors. The animals were allowed to settle in the animal quarters for several days before any experiments were started. The rats were anesthetized with 8% chloralhydrate in a dose corresponding to 3.5 ml/kg body weight. Heterotophic heart grafts were connected to the neck vessels using a nonsuture cuff technique. Rejection was defined as loss of regular palpable contraction and clinical signs of rejection.

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