{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:14:32Z","timestamp":1768450472229,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T00:00:00Z","timestamp":1468800000000},"content-version":"vor","delay-in-days":0,"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":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>5\u2010HT increases force and L\u2010type Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup> current (I<jats:sub>Ca,L<\/jats:sub>) and causes arrhythmias through 5\u2010HT<jats:sub>4<\/jats:sub> receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5\u2010HT are blunted, arrhythmias abolished but I<jats:sub>Ca,L<\/jats:sub> responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and\/or PDE4, using the inhibitors cilostamide (300\u00a0nM) and rolipram (1\u00a0\u03bcM) respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Contractile force, arrhythmic contractions and I<jats:sub>Ca,L<\/jats:sub> were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Maximum force responses to 5\u2010HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5\u2010HT in peAF and the inotropic potency of 5\u2010HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5\u2010HT were not decreased in peAF. Responses of I<jats:sub>Ca,L<\/jats:sub> to 5\u2010HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5\u2010HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>PDE3, but not PDE4, reduced inotropic responses to 5\u2010HT in peAF, independently of lusitropy and I<jats:sub>Ca,L<\/jats:sub>, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5\u2010HT to induce arrhythmias by inhibition of PDE3 plus PDE4.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13525","type":"journal-article","created":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T08:06:45Z","timestamp":1464595605000},"page":"2478-2489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["In permanent atrial fibrillation, PDE3 reduces force responses to 5\u2010HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias"],"prefix":"10.1111","volume":"173","author":[{"given":"Emanuel","family":"Berk","sequence":"first","affiliation":[{"name":"Department of Pharmacology Dresden University of Technology  Dresden Germany"},{"name":"Department of Experimental Pharmacology and Toxicology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Department of Internal Medicine II Municipal Hospital 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