CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 3, May/June 2015
108
AFRICA
were decreased during MMF therapy. This study suggested that
MMF therapy regulates the activation markers in B lymphocytes
while decreasing B lymphocyte counts.
A total of 22 orthotopic heart transplantations were
performed between April 1995 and February 2002 in the Onasis
Cardiac Surgery Centre.
18
Within this period, 532 patients were
selected and 223 were approved for pre-transplantation. AZA,
CYC and steroids were used for initial immunosuppression, with
MMF used instead of AZA in 16 patients. Gradually, AZA has
been completely replaced by MMF in cases that have exceeded
three years post transplant. A total of 19 patients were followed
for more than one year after transplantation and it was found
that one (5.3%) patient died, three (15.8%) developed rejection
and three (15.8%) coronary artery disease.
Klupp
et al.
19
divided rats that underwent allograft heart
transplantation into four groups, each including six rats. Each of
the groups receiving low- or high-doseMMFwas divided into two
subgroups. Pharmacokinetics (measured by high-performance
liquid chromatography), pharmacodynamics and histological
graft rejection scoring were performed in all animals on the
sixth day. Rejection scoring was found to be more associated
with MPA plasma concentration in terms of suppression of
lymphocyte proliferation and transferrin receptor expression.
Good lymphocyte suppression was provided in the low-dose
group (5 mg/kg MMF BID) and ongoing pharmacodynamics
were also good. No difference was found between low- and high-
dose groups in terms of rejection scores.
In initial clinical studies, MMF has been used instead of AZA
in triple therapies. In a randomised study comprising 50 patients
from 28 centres, MMF was compared with AZA in triple therapy
after cardiac transplantation. It was found that the need for
rejection therapy was decreased and the one-year mortality rate
was substantially reduced in the MMF group.
5
Pethig
et al.
21
investigated systemic inflammatory response in
patients who had undergone heart transplantation and had been
receiving immunosuppressive agents containing AZA or MMF.
Systemic inflammatory response was found to be lower in the
MMF group. High-quality, randomised studies have demonstrated
that MMF, when used together with CYC and steroids, reduced
the frequency and intensity of rejection and improved the grafts,
in patients who underwent heart and kidney transplantation.
22
A limitation of our
study was that the number of study
subjects was low. Also the efficacy of MMF was investigated
compared with only MP, but not with a control group. Since
MP is an immunosuppressive agent approved by the scientific
population, it was selected instead of placebo.
Conclusion
This study compared the effects of MMF and MP on duration
of motor activity and rejection rate of transplants in rabbits that
underwent retroperitoneal heterotopic heart transplantation. We
found that MMF caused statistically significantly longer duration
of motor activity in the transplanted hearts. No statistically
significant difference was found between the MMF and MP
groups in terms of transplant rejection rate. However, based on
the absence of a significant difference with MP, which is a potent
and important immunosuppressive agent in rescue therapy in
terms of prevention of rejection, we concluded that MMF is also
important for the prevention of rejection in transplantation.
References
1. Bayezid Ö.
Kalp Transplantasyonu
. Akdeniz Üniversitesi Yayını, Antalya,
2003, No: 86. ISBN: 975-7669-69-6.
2. Özgen AG.
Kalp Cerrahisi
. Dicle Üniversitesi Yayını, Diyarbakır, 1999.
ISBN: 975-7635-04-9.
3. Cohn LH, Edmunds LH.
Cardiac Surgery in Adults
, 2nd edn. New York,
2003. ISBN: 0-07-139129-0.
4. Paç M, Akçevin A, Aka A, Büket S, Sarıo
ğ
lu T. Kalp ve Damar Cerrahisi.
MN Medikal & Nobel Tıp, Ankara, 2004. ISBN: 975-567-028-9.
5. Ross H, Hendry P, Dipchand A,
et al
. Canadian Cardiovascular Society
Consensus Conference on Cardiac Transplantation 2001.
Can J Cardiol
2003;
19
(6): 620–654.
6. Wüthrich RP, Weinreich T, Ambühl PM, Candinas D, Binswanger U.
Reduced kidney transplant rejection rate and pharmacoeconomic advan-
tage of MMF.
Nephrol Dial Transpl
1999;
14
(2): 394–399.
7. Hunt SA. Current status of cardiac transplantation.
J Am Med Assoc
1998;
280
(19): 1692–1698.
8. Keogh A. Calcineurin ınhibitors in heart transplantation.
Heart Lung
Transpl
2004;
23
(5): 202–206.
9. Holt CD, Sievers TM, Ghobrial RM,
et al
. Mycophenolate mofetil
effects on clinical transplantation.
BioDrugs
1998;
10
(5): 373–384.
10. Clark C, Boyles S. Heart transplant patients to have option to prevent
rejection.
Blood Weekly
1998,
66
(4): 507–515.
11. Mathieu P, Carrier M, White M,
et al.
Effect of mycophenolate mofetil in
heart transplantation.
Can J Surg
2000;
43
(3): 202–206.
12. European Mycophenolate Mofetil Cooperative Study Group. Placebo-
controlled study of mycophenolate mofetil combined with cyclosporin
and corticosteroids for prevention of acute rejection.
Lancet
1995;
345
(8961): 1321–1325.
13. Dipchand AI, Benson L, McCrindle BW,
et al.
Mycophenolate mofetil in
pediatric heart transplant recipients: A single center experience.
Pediatr
Transpl
2001;
5
(2): 112–118.
14. Rose ML, Smith J, Dureau G,
et al
. Mycophenolate mofetil decreases
antibody production after cardiac transplantation.
J Heart Lung Traspl
2002;
21
(2): 282–285.
15. Gummert JF, Barten MJ, Bartsch P,
et al.
Pharmacodynamic (PD)
measurements of the immunsupressive effects of the combination of
cyclosporine (CY) and mycophenolate mofetil (MMF): correlation
between drug dose and lymphocyte function.
J Heart Lung Transpl
2001;
20
(2): 163.
16. Richter MC, Zahn S, Krause M,
et al
. Mycophenolate mofetil signifi-
cantly reduces leukocyte graft infiltration after heterotopic cardiac trans-
plantation in rat model comperative study with cyclosporine and FK 506.
J Heart Lung Transpl
2003;
22
(10): 1107–1116.
17. Weigel G, Griesmacher A, Karimi A,
et al.
Effect of mycophenolate
mofetil therapy on lymphocyte activation in heart transplant recipients.
J
Heart Lung Transpl
2002;
21
(10): 107–109.
18. Magginas A, Adamopoulos S, Karavolias G,
et al.
Orthotopic heart
transplantation: early clinical experience and results of a new transplan-
tation centre.
Hellenic J Cardiol
2003;
44
(4): 102–107.
19. Klupp J, Gelder T, Dambrin C,
et al.
Sustained suppression of peripheral
blood immune functions by trearment with mycophenolate mofetil corre-
lates with reduced severity of cardiac allograft rejection
. J Heart Lung
Transpl
2004;
23
(3): 334–351.
20. Pethig K, Heublein B, Wahlers T,
et al
. Mycophenolate mofetil for
secondary prevention of cardiac allograft vasculopathy: ınfluence on
ınflammation and progression of ıntımal hyperplasia.
J Heart Lung
Transpl
2004;
23
(1): 61–66.
21. Mele TS, Halloran PF. The use of mycophenolate mofetil in transplant
recipients.
Immunopharmacology
2000;
47
(2–3): 215–245.