High-dose stabilized chlorite matrix WF10 prolongs cardiac xenograft survival in the hamster-to-rat model without inducing ultrastructural or biochemical signs of cardiotoxicity.
WF10 is a stabilized chlorite matrix with immunosuppressive effects. In vitro studies have demonstrated its ability to suppress T cells and delay or abolish antigen presentation. Hence, WF10 may prove useful to prolong graft survival after transplantation. In this study, we evaluated the use of high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population, receiving high dose WF10 for 5 days, were compared with a matched control group. Ultrastructural examination of cardiac tissue as well as biochemical analysis of the cardiac enzymes troponin I, myoglobin and MB isoenzyme of creatine kinase showed no signs of damage. Thus, while prolonging graft survival, high dose WF10 seems to be non-cardiotoxic and as such should not contribute to the differential diagnosis of acute graft failure.
Hansen
A
A
Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. alha@herlevhosp.kbhamt.dk
Kemp
K
K
Kemp
E
E
Bouchelouche
K
K
Bouchelouche
P
P
Dieperink
H
H
Horn
T
T
Larsen
S
S
D000818:Animals; D002713:Chlorine / Q000008:administration & dosage*; D003402:Creatine Kinase / Q000378:metabolism; D052279:Creatine Kinase, MB Form; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D008647:Mesocricetus; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009210:Myofibrils / Q000187:drug effects / Q000648:ultrastructure; D009211:Myoglobin / Q000378:metabolism; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000473:pathology*; D019210:Troponin I / Q000378:metabolism
D007527:Isoenzymes; D009211:Myoglobin; D010087:Oxides; D019210:Troponin I; D002713:Chlorine; C041955:tetrachlorodecaoxide; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form