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The Journal of Thoracic and Cardiovascular Surgery, Vol 97, 841-854, Copyright © 1989 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
GE Sarris, RS Mitchell, ME Billingham, JR Glasson, PD Cahill and DC Miller
Accelerated coronary arteriosclerosis remains the most important factor
limiting long-term survival of heart transplant recipients, and dietary
fish oil supplementation with omega-3 polyunsaturated fatty acids has been
suggested to have a protective effect against coronary disease in
epidemiologic studies and to inhibit arteriosclerosis in animal
experiments. Therefore we tested the hypothesis that fish oil
administration inhibits the development of allograft coronary
arteriosclerosis by using a heterotopic heart transplant model. Three
groups of Lewis rats (n = 10 each) received heterotopic heart transplants
from Brown-Norway donors and were treated with cyclosporine
intraperitoneally on a tapering schedule. Group 1 received fish oil daily
by gavage (2 ml/kg/day; Emulsified Super MaxEpa, Twin Labs, Ronkonkona,
N.Y.). Group 2 received an equal amount of safflower oil, as well as
aspirin (1 mg/kg/day) and dipyridamole (3 mg/kg/day). Group 3 received
safflower oil only. All rats were put to death 110 days later, at which
time there was no statistically significant difference in graft function as
assessed by palpation (scale 0 to 4, mean = 3.7 +/- 0.5 [+/- standard
deviation]; analysis of variance: p = 0.72) or in microscopic grade of
rejection (scale, 0 = none to 3 = severe, mean 2.1 +/- 0.6; analysis of
variance: p = 0.68) between any of the groups. The coronary arteries were
histologically scored for the degree of arteriosclerosis (scale, 0 = normal
to 3 = occluded), and a mean grade of coronary disease was calculated for
each heart. The fish oil-treated group had significantly less severe
allograft coronary arteriosclerosis (analysis of variance: p = 0.005) than
did groups 2 and 3 (mean grade 0.23 +/- 0.22 versus 1.04 +/- 0.75 and 0.96
+/- 0.55 (p less than 0.05, Scheffe F test), whereas groups 2 and 3 had
similar degrees of coronary disease (p = no significant difference). These
data demonstrate that fish oil supplementation inhibited accelerated
coronary arteriosclerosis in this cyclosporine-treated heart allograft rat
model, whereas antiplatelet agents in these doses were ineffective.
Although the mechanism of this protective effect remains incompletely
understood, it does not appear to involve enhanced immunosuppression. Fish
oil and specific omega-3 polyunsaturated fatty acids should be further
investigated as potentially useful agents to ameliorate accelerated
allograft coronary arteriosclerosis in other animal species and perhaps
eventually in man.
ARTICLES
Inhibition of accelerated cardiac allograft arteriosclerosis by fish oil
Department of Cardiovascular Surgery, Stanford University School of Medicine, Calif.
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