Effects of eicosapentaenoic acid and docosahexaenoic acid diet supplement on tolerance to the cardiotoxicity of epirubicin and to ischaemia reperfusion in the isolated rat heart.
We compared the effects of 2 weeks dietary supplement of docosahexaenoic acid, eicosapentaenoic acid or olive oil on myocardial tolerance to the cardiotoxicity of the anthracycline epirubicin and to ischaemia reperfusion. Isolated rat hearts from the dietary groups were perfused at a constant flow rate of 12.5 ml/min. The hearts were subjected to a 20 min. period of epirubicin infusion by a side arm of the perfusion system at a rate of 0.2 mg/min. or a 20 min. period of global ischaemia. After 10 min. of epirubicin infusion a significantly (P < 0.05) higher aortic pressure (an index of coronary resistance during constant flow perfusion) was observed in the olive oil group; 130 +/- 22% (mean +/- S.D.) compared to hearts in the docosahexaenoic acid; 108 +/- 9% (mean +/- S.D.), and eicosapentaenoic acid; 105 +/- 7% (mean +/- S.D.), group. Hearts from docosahexaenoic acid-fed rats showed a significantly increased left ventricular end-diastolic pressure (an index of contracture); of 66 +/- 30 mmHg (mean +/- S.D.) after 15 min. of global ischaemia compared to eicosapetaenoic acid fed rats; 37 +/- 18 mmHg (mean +/- S.D.), and significantly higher release of lactate dehydrogenase during the following 30 min. period of reperfusion compared to olive oil-fed rats. We conclude that eicosapentaenoic acid and docosahexaenoic acid could be useful during epirubicin infusion and that docosahexaenoic acid could be harmful during ischaemia reperfusion.
Schjøtt
J
J
Department of Pharmacology and Toxicology, University Medical Center, University of Trondheim, Norway.
Brurok
H
H
Jynge
P
P
Bjerve
K S
KS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015251:Epirubicin / Q000633:toxicity*; D005527:Food, Fortified; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase; D008297:Male; D009206:Myocardium / Q000378:metabolism; D000069463:Olive Oil; D010743:Phospholipids / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology
D000903:Antibiotics, Antineoplastic; D004042:Dietary Fats, Unsaturated; D000069463:Olive Oil; D010743:Phospholipids; D010938:Plant Oils; D004281:Docosahexaenoic Acids; D015251:Epirubicin; D015118:Eicosapentaenoic Acid; D007770:L-Lactate Dehydrogenase