Dietary omega-3 supplementation exacerbates left ventricular dysfunction in an ovine model of anthracycline-induced cardiotoxicity.
BACKGROUND
Cumulative dose-dependent nonischemic cardiomyopathy (NICM) remains a significant risk with the use of some chemotherapeutic agents. In this context, omega-3 polyunsaturated fatty acids (PUFA) have been investigated for their cardioprotective potential in rodent and in vitro models of anthracycline toxicity, with conflicting results. This study evaluated prophylactic omega-3 PUFA supplementation in a large-animal model of anthracycline-induced NICM.


RESULTS
Merino sheep were randomized to oral drenching with omega-3 PUFA (fish oil; n = 8) or olive oil placebo (n = 9) 3 weeks before commencing repeated intracoronary infusions of doxorubicin (DOX) to induce cardiac dysfunction. Cumulative DOX dose was 3.6 mg/kg. Drenching was continued for 12 weeks after final DOX exposure. Despite significant increases in tissue omega-3 PUFA levels (P < .05 vs placebo), omega-3-treated sheep displayed greater signs of anthracycline cardiotoxicity than placebo animals, consisting of left ventricular dilatation and a greater decline in ejection fraction (P < .05), although myocardial fibrosis burden was similar in both groups.


CONCLUSIONS
Dietary intake of omega-3 PUFA fails to prevent and may indeed exacerbate DOX-induced cardiotoxicity. Clinical use of omega-3 supplementation during chemotherapy should be deferred until more information is available regarding the mechanisms of interaction between fatty acids and the myocardium during anthracycline exposure.
Discipline of Medicine, Faculty of Health Sciences, University of Adelaide and Cardiovascular Research Centre, Royal Adelaide Hospital, Adelaide, Australia.
Angelo
A
Carbone
Peter J
PJ
Psaltis
Adam J
AJ
Nelson
Robert
R
Metcalf
James D
JD
Richardson
Michael
M
Weightman
Anthony
A
Thomas
John W
JW
Finnie
Glenn D
GD
Young
Stephen G
SG
Worthley
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004032:Diet; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D012756:Sheep; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*; D020257:Ventricular Remodeling / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D015525:Fatty Acids, Omega-3; D004317:Doxorubicin