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In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)\u2010induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5\u2010(tetradecyloxy)\u20102\u2010furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high\u2010energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile\u2010induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA \u201cwash\u2010out.\u201d Although the development and severity of amphiphile\u2010induced myocyte injury could be correlated with both the intracellular TOFA\/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid \u03b2 oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile\u2010induced bioenergetic abnormalities appeared to constitute a state of \u201cmetabolic anoxia\u201d underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.<\/jats:p>","DOI":"10.1002\/jcp.1041370102","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T10:55:56Z","timestamp":1109415356000},"page":"1-13","source":"Crossref","is-referenced-by-count":15,"title":["Amphiphile\u2010induced heart muscle\u2010cell (Myocyte) injury: Effects of intracellular fatty acid overload"],"prefix":"10.1002","volume":"137","author":[{"given":"David R.","family":"Janero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Burghardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38027-5"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/o85-147"},{"key":"e_1_2_1_4_1","first-page":"1196","volume-title":"Methods of Enzymatic Analysis","author":"Bergmeyer H. 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