{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:43:36Z","timestamp":1791107016444,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2677,"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":[[2001,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The structural conformation of diadenosine tetraphosphate (Ap<jats:sub>4<\/jats:sub>A) and pentaphosphate (Ap<jats:sub>5<\/jats:sub>A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap<jats:sub>4<\/jats:sub>A and Ap<jats:sub>5<\/jats:sub>A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap<jats:sub>4<\/jats:sub>A and Ap<jats:sub>5<\/jats:sub>A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap<jats:sub>4<\/jats:sub>A has any electrophysiological or antiarrhythmic effects during ischaemia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff\u2010perfused guinea\u2010pig hearts under constant flow conditions. The effects of 1\u2003n<jats:sc>M<\/jats:sc> and 1\u2003\u03bc<jats:sc>M<\/jats:sc> Ap<jats:sub>4<\/jats:sub>A and Ap<jats:sub>5<\/jats:sub>A were studied at pH 7.4, 6.5 and 8.5. The effects of 1\u2003\u03bc<jats:sc>M<\/jats:sc> Ap<jats:sub>4<\/jats:sub>A were studied during global low\u2010flow ischaemia and reperfusion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At pH 7.4, Ap<jats:sub>4<\/jats:sub>A and Ap<jats:sub>5<\/jats:sub>A increased action potential duration (APD<jats:sub>95<\/jats:sub>) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap<jats:sub>4<\/jats:sub>A increased RP but the effects of Ap<jats:sub>4<\/jats:sub>A and Ap<jats:sub>5<\/jats:sub>A on perfusion pressure were attenuated. During ischaemia, Ap<jats:sub>4<\/jats:sub>A had no antiarrhythmic or electrophysiological effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data demonstrate the importance of extracellular pH in influencing the effects of Ap<jats:sub>4<\/jats:sub>A and Ap<jats:sub>5<\/jats:sub>A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 639\u2013647; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704288\">10.1038\/sj.bjp.0704288<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704288","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T22:03:41Z","timestamp":1106949821000},"page":"639-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate"],"prefix":"10.1111","volume":"134","author":[{"given":"Brigitte M","family":"Stavrou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003950050186"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200001150-00004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003800070045"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(00)01659-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.5.513"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017833"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.4034"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1978.sp012499"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00697.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100140520"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1344"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(96)00100-3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-445X.1999.01773.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00004-8"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.3.365"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1981.sp013655"},{"key":"e_1_2_7_18_1","first-page":"1453","article-title":"HMR 1883, a novel cardioselective inhibitor of the ATP\u2010sensitive potassium channel. 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