{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:49:53Z","timestamp":1789865393992,"version":"4.0.1"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2000,2,18]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Arachidonic acid (AA) and other nonesterified fatty acids (FAs) have been shown to exert harmful effects during cardiac ischemia. By continuously measuring intracellular pH (pH\n            <jats:sub>i<\/jats:sub>\n            ) changes in neonatal and adult cardiac myocytes, we have found, for the first time, that 10 \u03bcmol\/L AA induces a substantial intracellular acidosis (0.3 to 0.4 pH units). We have ruled out the possibilities that the AA-induced acidosis is caused by (1) inhibition or stimulation of the pH\n            <jats:sub>i<\/jats:sub>\n            regulators, (2) protein kinase C activation or the generation of AA metabolites or free radicals, or (3) activation of NADPH oxidase or an inward H\n            <jats:sup>+<\/jats:sup>\n            current. The AA-induced acidosis fits to a simple diffusion mechanism, as proposed by Kamp and Hamilton (flip-flop model) for artificial phospholipid bilayers. The important properties found in the cardiac myocyte are that (1) the initial rate of acid flux (J\n            <jats:sub>H<\/jats:sub>\n            ) increases with the AA concentration (2 to 50 \u03bcmol\/L), (2) FAs with a\n            <jats:sup>\u2212<\/jats:sup>\n            COOH group (eg, AA, oleic acid, and linoleic acid) induce intracellular acidification, but FAs with a\n            <jats:sup>\u2212<\/jats:sup>\n            COOCH\n            <jats:sub>3<\/jats:sub>\n            group (eg, AA methyl ester) have little effect on the pH\n            <jats:sub>i<\/jats:sub>\n            , (3) tetradecylamine (FA amine) induces intracellular alkalosis, and, most importantly, (4) both the AA- and tetradecylamine-induced pH\n            <jats:sub>i<\/jats:sub>\n            changes can be reversed by 0.3% BSA. Because a low concentration of AA (10 \u03bcmol\/L) can induce a substantial acidosis, the possible involvement of the FA-evoked acidosis in the negative inotropic effect during cardiac ischemia is discussed. The full text of this article is available at http:\/\/www.circresaha.org.\n          <\/jats:p>","DOI":"10.1161\/01.res.86.3.e55","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Possible Mechanism(s) of Arachidonic Acid\u2013Induced Intracellular Acidosis in Rat Cardiac Myocytes"],"prefix":"10.1161","volume":"86","author":[{"given":"Mei-Lin","family":"Wu","sequence":"first","affiliation":[{"name":"From the Institutes of Physiology (M.-L.W., C.-C.C.) and Pharmacology (M.-J.S.), College of Medicine, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chiang","family":"Chan","sequence":"additional","affiliation":[{"name":"From the Institutes of Physiology (M.-L.W., C.-C.C.) and Pharmacology (M.-J.S.), College of Medicine, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Ja","family":"Su","sequence":"additional","affiliation":[{"name":"From the Institutes of Physiology (M.-L.W., C.-C.C.) and Pharmacology (M.-J.S.), College of Medicine, National Taiwan University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)90012-4"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(95)00016-O"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.50.4.7067061"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.54.3.6421507"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.67.4.2119911"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00370692"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.263.2.C494"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.14.6452"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74254-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.100.6.1021"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.59.3.2429781"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.258.6.C967"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017268"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1978.sp012231"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.89.6.1015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00217-9"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31900-2"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10139"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.23.11367"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00092a017"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00037a034"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)33287-9"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(80)90442-3"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37606-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.11.5909"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(93)81198-6"},{"key":"e_1_3_2_27_2","first-page":"27289","volume":"269","year":"1994","unstructured":"Nanda A, Romanek R, Curnutte JT, Grinstein S. 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