Accelerated
coronary atherosclerosis of cardiac allograft occurs in 30-40% of cardiac transplant patients and remains an unsolved clinical problem. The etiology is unknown and anti-platelet drugs are used without conspicuous success. The inhibitory effect of the octapeptide,
angiopeptin on
coronary atherosclerosis was studied in a previously described rabbit heterotopic cardiac transplant model where allograft rejection is prevented by daily administration of
cyclosporin A (CsA, 10 mg/kg per day s.c.). Twenty male New Zealand white rabbits (2.6-2.8 kg) received a heterotopic cardiac transplant from rabbits of the same strain. Donors and recipients were fed a 0.5%
cholesterol diet 1 week prior to
transplantation which was continued for the recipient until death 6 weeks later. The control group (n = 16) received CsA and saline
injections twice daily and the treatment group (n = 4) received CsA and
angiopeptin (60 micrograms/rabbit daily s.c.) in 2 divided doses. The treatment began after completion of the
transplantation. Coronary artery transplant
atherosclerosis was uniformly distributed (tubular) in the entire length of the coronary arteries.
Angiopeptin inhibited the intimal
hyperplasia in the transplanted heart from 47.5 +/- 2.4% (mean +/- SE) to 25.0 +/- 6.9% and in the native heart from 24.2 +/- 1.4% to 15.7 +/- 1.5%. The intimal
hyperplasia is expressed as area of intimal
hyperplasia/total vessel area x 100%. A similar inhibition by
angiopeptin was seen in
lipid deposition in the donor ascending aorta which is transplanted with the heart.
Angiopeptin attenuated significantly the
hyperplasia and the
lipid deposition of the native coronary arteries and aorta but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)