Cyclosporine does not enhance the development of accelerated coronary artery disease: experimental study in a rat cardiac transplant model.
BACKGROUND
Among other factors, cyclosporine (CsA) is linked with the development of accelerated coronary artery disease (ACAD) after transplantation. The objective of this study was to assess the influence of different CsA regimens on ACAD after rat heart transplantation.


METHODS
After heterotopic cardiac transplantation (Lewis to Fisher), animals were treated with 3 or 12 mg/kg per day of CsA, administered subcutaneously. The control group received no therapy. CsA blood levels were determined every 10 days. Twenty and 80 days after grafting, the incidence of ACAD was determined and the extent of ACAD was assessed as mean vessel occlusion (mvo).


RESULTS
In the 12-mg group, CsA levels were nearly 10-fold higher than in the 3-mg group. Only in the 12-mg CsA group was the incidence of ACAD significantly reduced at Days 20 and 80 when compared with controls. Continuous therapy with 3 mg and 12 mg of CsA significantly reduced the mvo at Days 20 and 80 when compared with control animals (p <.05). However, comparing the two dosages, there were no significant differences. When the 20-day-limited course of CsA application was used we did not observe significant differences in mvo at Day 80 upon comparison of 3-mg and 12-mg CsA treatment versus untreated animals.


CONCLUSIONS
Despite the excessive increase in CsA blood levels we observed neither a further reduction nor an increase of ACAD in the high-dose group compared with the low-dose group. Therefore, CsA did not enhance the development of chronic rejection in this experiment.
Richter
Markus
M
Department of Cardiac Surgery, Heart Center, University of Leipzig, Leipzig, Germany. drichter@gmx.net
Skupin
Manfred
M
Schramm
David
D
Weinert
Marc
M
Richter
Heike
H
Mohr
Friedrich Wilhelm
FW
Olbrich
Hans Georg
HG
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D023903:Coronary Restenosis / Q000188:drug therapy / Q000517:prevention & control; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000178:diet therapy / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008955:Models, Cardiovascular; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects; D028761:Withholding Treatment
D007166:Immunosuppressive Agents; D016572:Cyclosporine