{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:43:50Z","timestamp":1792514630491,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":212,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Increased activity of the Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010exchanger (NHE\u20101) in heart failure underlies raised [Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>causing disturbances of calcium handling. Inhibition of NHE\u20101, initiated at the onset of pressure\/volume overload, prevents development of hypertrophy, heart failure and remodelling. We hypothesized that chronic inhibition of NHE\u20101, initiated at a later stage, would induce regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Development of heart failure in rabbits was monitored electrocardiographically and echocardiographically, after one or three months. Cardiac myocytes were also isolated. One group of animals were treated with cariporide (inhibitor of NHE\u20101) in the diet after one month. Cytoplasmic calcium, sodium and action potentials were measured with fluorescent markers and sarcoplasmic reticulum calcium content by rapid cooling. Calcium after\u2010transients were elicited after rapid pacing. Sodium channel current<jats:italic>(I<\/jats:italic><jats:sub>Na<\/jats:sub>) was measured using patch\u2010clamp techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Hypertrophy and heart failure developed after one month and progressed during the next two months. After one month, dietary treatment with cariporide was initiated. Two months of treatment reduced hypertrophy and heart failure, duration of action potential QT\u2010interval and QRS, and restored sodium and calcium handling and the incidence of calcium after\u2010transients. In cardiac myocytes, parameters of<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>were not changed by cariporide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications:<\/jats:title><jats:p>In rabbit hearts with hypertrophy and signs of heart failure one month after induction of pressure\/volume overload, two months of dietary treatment with the NHE\u20101 inhibitor cariporide caused regression of hypertrophy, heart failure and ionic and electrophysiological remodelling.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2008)<jats:bold>154<\/jats:bold>, 1266\u20131275; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.189\">10.1038\/bjp.2008.189<\/jats:ext-link>; published online 19 May 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/bjp.2008.189","type":"journal-article","created":{"date-parts":[[2008,5,20]],"date-time":"2008-05-20T15:39:17Z","timestamp":1211297957000},"page":"1266-1275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Chronic inhibition of the Na<sup>+<\/sup>\/H<sup>+<\/sup>\u2010 exchanger causes regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling"],"prefix":"10.1111","volume":"154","author":[{"given":"A","family":"Baartscheer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hardziyenka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C N 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