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Title: Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (USA)
;  [1];  [2];  [3]
  1. Harvard Medical School, Boston, MA (USA)
  2. Univ. Munchen, (Germany)
  3. Brigham and Women's Hospital, Boston, MA (USA)

Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3{endash}5 days in culture medium enriched with 5 {mu}M arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3{endash}5 days with 5 {mu}M eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable {sup 86}Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 {plus minus} 29 and 757 {plus minus} 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3{endash}5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes.

OSTI ID:
5584190
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:20; ISSN 0027-8424
Country of Publication:
United States
Language:
English

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