{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:35:41Z","timestamp":1789900541595,"version":"4.0.1"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/12\/57\/29717"],"award-info":[{"award-number":["FS\/12\/57\/29717"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CH200004\/12801"],"award-info":[{"award-number":["CH200004\/12801"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/15\/28\/31476"],"award-info":[{"award-number":["FS\/15\/28\/31476"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/10\/71\/28563"],"award-info":[{"award-number":["FS\/10\/71\/28563"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/15\/70\/31724"],"award-info":[{"award-number":["PG\/15\/70\/31724"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["IG\/15\/2\/31514"],"award-info":[{"award-number":["IG\/15\/2\/31514"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/09\/002\/26487"],"award-info":[{"award-number":["FS\/09\/002\/26487"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/12\/34\/29565"],"award-info":[{"award-number":["FS\/12\/34\/29565"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/15\/67\/32038"],"award-info":[{"award-number":["FS\/15\/67\/32038"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/10\/52\/28678"],"award-info":[{"award-number":["FS\/10\/52\/28678"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K500823\/1"],"award-info":[{"award-number":["MR\/K500823\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K501211\/1"],"award-info":[{"award-number":["MR\/K501211\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heart failure (HF) is characterized by poor survival, a loss of catecholamine reserve and cellular structural remodeling in the form of disorganization and loss of the transverse tubule network. Indeed, survival rates for HF are worse than many common cancers and have not improved over time. Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile dysfunction. Using a sheep model of advanced HF, we show that tadalafil treatment improves contractile function, reverses transverse tubule loss, restores calcium transient amplitude and the heart\u2019s response to catecholamines. Accompanying these effects, tadalafil treatment normalized BNP mRNA and prevented development of subjective signs of HF. These effects were\u00a0independent of changes in myocardial cGMP content and were associated with upregulation of both monomeric and dimerized forms of protein kinase G and of the cGMP hydrolyzing phosphodiesterases 2 and 3. We propose that the molecular switch for the loss of transverse tubules in HF and their restoration following tadalafil treatment involves the BAR domain protein Amphiphysin II (BIN1) and the restoration of catecholamine sensitivity is through reductions in G-protein receptor kinase 2, protein phosphatase 1 and protein phosphatase 2\u2009A abundance following phosphodiesterase 5 inhibition.<\/jats:p>","DOI":"10.1038\/s41598-019-42592-1","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T06:02:54Z","timestamp":1556690574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure"],"prefix":"10.1038","volume":"9","author":[{"given":"Michael","family":"Lawless","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8616-318X","authenticated-orcid":false,"given":"Jessica L.","family":"Caldwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-4812","authenticated-orcid":false,"given":"Emma J.","family":"Radcliffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E. R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-133X","authenticated-orcid":false,"given":"George W. P.","family":"Madders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Hutchings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori S.","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Church","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Unwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme J.","family":"Kirkwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-6911","authenticated-orcid":false,"given":"Lorenz K.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-9817","authenticated-orcid":false,"given":"Charles M.","family":"Pearman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca F.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Eisner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine M.","family":"Dibb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2770-445X","authenticated-orcid":false,"given":"Andrew. W.","family":"Trafford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"42592_CR1","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1113\/jphysiol.2010.203984","volume":"589","author":"SJ Briston","year":"2011","unstructured":"Briston, S. J. et al. Impaired \u03b2-adrenergic responsiveness accentuates dysfunctional excitation-contraction coupling in an ovine model of tachypacing-induced heart failure. J Physiol 589, 1367\u20131382, https:\/\/doi.org\/10.1113\/jphysiol.2010.203984 (2011).","journal-title":"J Physiol"},{"key":"42592_CR2","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1161\/CIRCULATIONAHA.106.632745","volume":"114","author":"BA Borlaug","year":"2006","unstructured":"Borlaug, B. A. et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 114, 2138\u20132147, https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.106.632745 (2006).","journal-title":"Circulation"},{"key":"42592_CR3","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr447","author":"PWJ Raake","year":"2012","unstructured":"Raake, P. W. J. et al. AAV6.\u03b2ARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J. https:\/\/doi.org\/10.1093\/eurheartj\/ehr447 (2012).","journal-title":"Eur Heart J"},{"key":"42592_CR4","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.cardiores.2003.11.005","volume":"61","author":"A El-Armouche","year":"2004","unstructured":"El-Armouche, A., Pamminger, T., Ditz, D., Zolk, O. & Eschenhagen, T. Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts. Cardiovasc Res 61, 87\u201393, https:\/\/doi.org\/10.1016\/j.cardiores.2003.11.005 (2004).","journal-title":"Cardiovasc Res"},{"key":"42592_CR5","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1126\/science.1185988","volume":"327","author":"VO Nikolaev","year":"2010","unstructured":"Nikolaev, V. O. et al. \u03b22-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science 327, 1653\u20131657, https:\/\/doi.org\/10.1126\/science.1185988 (2010).","journal-title":"Science"},{"key":"42592_CR6","doi-asserted-by":"publisher","first-page":"H1841","DOI":"10.1152\/ajpheart.1999.277.5.H1841","volume":"277","author":"MA Laflamme","year":"1999","unstructured":"Laflamme, M. A. & Becker, P. L. Gs and adenylyl cyclase in transverse tubules of heart: implications for cAMP-dependent signaling. Am J Physiol 277, H1841\u20131848, https:\/\/doi.org\/10.1152\/ajpheart.1999.277.5.H1841 (1999).","journal-title":"Am J Physiol"},{"key":"42592_CR7","doi-asserted-by":"publisher","first-page":"e00038","DOI":"10.1002\/phy2.38","volume":"1","author":"C Cros","year":"2013","unstructured":"Cros, C. & Brette, F. Functional subcellular distribution of \u03b21- and \u03b22-adrenergic receptors in rat ventricular cardiac myocytes. Physiol Rep 1, e00038, https:\/\/doi.org\/10.1002\/phy2.38 (2013).","journal-title":"Physiol Rep"},{"key":"42592_CR8","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/CIRCRESAHA.116.303448","volume":"115","author":"JL Caldwell","year":"2014","unstructured":"Caldwell, J. L. et al. Dependence of cardiac transverse tubules on the BAR domain protein amphiphysin II (BIN-1). Circ Res 115, 986\u2013996, https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.303448 (2014).","journal-title":"Circ Res"},{"key":"42592_CR9","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/S0008-6363(00)00256-X","volume":"49","author":"J He","year":"2001","unstructured":"He, J. et al. Reduction in density of transverse tubules and L-type Ca(2+) channels in canine tachycardia-induced heart failure. Cardiovasc Res 49, 298\u2013307, https:\/\/doi.org\/10.1016\/S0008-6363(00)00256-X (2001).","journal-title":"Cardiovasc Res"},{"key":"42592_CR10","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1113\/jphysiol.2006.107227","volume":"574","author":"WE Louch","year":"2006","unstructured":"Louch, W. E. et al. T-tubule disorganization and reduced synchrony of Ca2+ release in murine cardiomyocytes following myocardial infarction. J Physiol 574, 519\u2013533, https:\/\/doi.org\/10.1113\/jphysiol.2006.107227 (2006).","journal-title":"J Physiol"},{"key":"42592_CR11","doi-asserted-by":"publisher","first-page":"e17901","DOI":"10.1371\/journal.pone.0017901","volume":"6","author":"DJ Crossman","year":"2011","unstructured":"Crossman, D. J., Ruygrok, P. N., Soeller, C. & Cannell, M. B. Changes in the organization of excitation-contraction coupling structures in failing human heart. PLoS One 6, e17901, https:\/\/doi.org\/10.1371\/journal.pone.0017901 (2011).","journal-title":"PLoS One"},{"key":"42592_CR12","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.pharmthera.2009.02.009","volume":"122","author":"EJ Tsai","year":"2009","unstructured":"Tsai, E. J. & Kass, D. A. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther 122, 216\u2013238, https:\/\/doi.org\/10.1016\/j.pharmthera.2009.02.009 (2009).","journal-title":"Pharmacol Ther"},{"key":"42592_CR13","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1096\/fj.00-0538com","volume":"15","author":"H Senzaki","year":"2001","unstructured":"Senzaki, H. et al. Cardiac phosphodiesterase 5 (cGMP-specific) modulates \u03b2-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 15, 1718\u20131726 (2001).","journal-title":"FASEB J"},{"key":"42592_CR14","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1161\/CIRCULATIONAHA.106.643536","volume":"115","author":"E Takimoto","year":"2007","unstructured":"Takimoto, E. et al. Compartmentalization of cardiac \u03b2-adrenergic inotropy modulation by phosphodiesterase type 5. Circulation 115, 2159\u20132167, https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.106.643536 (2007).","journal-title":"Circulation"},{"key":"42592_CR15","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1161\/CIRCRESAHA.110.226712","volume":"107","author":"LRV Castro","year":"2010","unstructured":"Castro, L. R. V., Schittl, J. & Fischmeister, R. Feedback control through cGMP-dependent protein kinase contributes to differential regulation and compartmentation of cGMP in rat cardiac myocytes. Circ Res 107, 1232\u20131240, https:\/\/doi.org\/10.1161\/CIRCRESAHA.110.226712 (2010).","journal-title":"Circ Res"},{"key":"42592_CR16","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1161\/01.RES.0000152262.22968.72","volume":"96","author":"E Takimoto","year":"2005","unstructured":"Takimoto, E. et al. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res 96, 100\u2013109, https:\/\/doi.org\/10.1161\/01.RES.0000152262.22968.72 (2005).","journal-title":"Circ Res"},{"key":"42592_CR17","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1161\/CIRCRESAHA.110.230698","volume":"108","author":"A Stangherlin","year":"2011","unstructured":"Stangherlin, A. et al. cGMP signals modulate cAMP levels in a compartment-specific manner to regulate catecholamine-dependent signaling in cardiac myocytes. Circ Res 108, 929\u2013939, https:\/\/doi.org\/10.1161\/CIRCRESAHA.110.230698 (2011).","journal-title":"Circ Res"},{"key":"42592_CR18","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.jacc.2013.05.057","volume":"62","author":"H Mehel","year":"2013","unstructured":"Mehel, H. et al. Phosphodiesterase-2 is up-regulated in human failing hearts and blunts \u03b2-adrenergic responses in cardiomyocytes. J Am Coll Cardiol 62, 1596\u20131606, https:\/\/doi.org\/10.1016\/j.jacc.2013.05.057 (2013).","journal-title":"J Am Coll Cardiol"},{"key":"42592_CR19","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1136\/heartjnl-2015-309223","volume":"102","author":"SG Anderson","year":"2016","unstructured":"Anderson, S. G. et al. Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality. Heart 102, 1750\u20131756, https:\/\/doi.org\/10.1136\/heartjnl-2015-309223 (2016).","journal-title":"Heart"},{"key":"42592_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0185-3","volume":"12","author":"E Giannetta","year":"2014","unstructured":"Giannetta, E. et al. Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials. BMC Med 12, 185, https:\/\/doi.org\/10.1186\/s12916-014-0185-3 (2014).","journal-title":"BMC Med"},{"key":"42592_CR21","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1161\/CIRCHEARTFAILURE.110.944694","volume":"4","author":"M Guazzi","year":"2011","unstructured":"Guazzi, M., Vicenzi, M., Arena, R. & Guazzi, M. D. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail 4, 8\u201317, https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.110.944694 (2011).","journal-title":"Circ Heart Fail"},{"key":"42592_CR22","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1161\/HYPERTENSIONAHA.111.180968","volume":"59","author":"Y-P Xie","year":"2012","unstructured":"Xie, Y.-P. et al. Sildenafil prevents and reverses transverse-tubule remodeling and Ca2+ handling dysfunction in right ventricle failure induced by pulmonary artery hypertension. Hypertension 59, 355\u2013362, https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.111.180968 (2012).","journal-title":"Hypertension"},{"key":"42592_CR23","doi-asserted-by":"publisher","first-page":"H1398","DOI":"10.1152\/ajpheart.91438.2007","volume":"294","author":"FN Salloum","year":"2008","unstructured":"Salloum, F. N. et al. Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice. Am J Physiol Heart Circ Physiol 294, H1398\u20131406, https:\/\/doi.org\/10.1152\/ajpheart.91438.2007 (2008).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"42592_CR24","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/sj.bjp.0705658","volume":"141","author":"O Nagy","year":"2004","unstructured":"Nagy, O., Hajnal, A., Parratt, J. R. & V\u00e9gh, A. Sildenafil (Viagra) reduces arrhythmia severity during ischaemia 24\u2009h after oral administration in dogs. Br J Pharmacol 141, 549\u2013551, https:\/\/doi.org\/10.1038\/sj.bjp.0705658 (2004).","journal-title":"Br J Pharmacol"},{"key":"42592_CR25","doi-asserted-by":"publisher","first-page":"H1263","DOI":"10.1152\/ajpheart.00324.2002","volume":"283","author":"R Ockaili","year":"2002","unstructured":"Ockaili, R., Salloum, F., Hawkins, J. & Kukreja, R. C. Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial KATP channels in rabbits. Am J Physiol Heart Circ Physiol 283, H1263\u20131269, https:\/\/doi.org\/10.1152\/ajpheart.00324.2002 (2002).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"42592_CR26","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0008-6363(03)00435-8","volume":"59","author":"T Reffelmann","year":"2003","unstructured":"Reffelmann, T. & Kloner, R. A. Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. Cardiovasc Res 59, 441\u2013449 (2003).","journal-title":"Cardiovasc Res"},{"key":"42592_CR27","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/aps.2016.13","volume":"37","author":"CK Huang","year":"2016","unstructured":"Huang, C. K. et al. Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model. Acta Pharmacol Sin 37, 473\u2013482, https:\/\/doi.org\/10.1038\/aps.2016.13 (2016).","journal-title":"Acta Pharmacol Sin"},{"key":"42592_CR28","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nm1175","volume":"11","author":"E Takimoto","year":"2005","unstructured":"Takimoto, E. et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11, 214\u2013222, https:\/\/doi.org\/10.1038\/nm1175 (2005).","journal-title":"Nat Med"},{"key":"42592_CR29","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jacc.2008.08.069","volume":"53","author":"T Nagayama","year":"2009","unstructured":"Nagayama, T. et al. Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol 53, 207\u2013215, https:\/\/doi.org\/10.1016\/j.jacc.2008.08.069 (2009).","journal-title":"J Am Coll Cardiol"},{"key":"42592_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-015-1317-8","volume":"4","author":"K Eskesen","year":"2015","unstructured":"Eskesen, K. et al. Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation. Springerplus 4, 592, https:\/\/doi.org\/10.1186\/s40064-015-1317-8 (2015).","journal-title":"Springerplus"},{"issue":"12","key":"42592_CR31","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1093\/gerona\/glv217","volume":"71","author":"Margaux A. Horn","year":"2015","unstructured":"Horn, M. A. et al. Temporal Development of Autonomic Dysfunction in Heart Failure: Effects of Age in an Ovine Rapid-pacing Model. J Gerontol A Biol Sci Med Sci, https:\/\/doi.org\/10.1093\/gerona\/glv217 (2015).","journal-title":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences"},{"key":"42592_CR32","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1161\/CIRCHEARTFAILURE.109.852228","volume":"2","author":"KM Dibb","year":"2009","unstructured":"Dibb, K. M. et al. Characterization of an extensive transverse tubular network in sheep atrial myocytes and its depletion in heart failure. Circ Heart Fail 2, 482\u2013489, https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.109.852228 (2009).","journal-title":"Circ Heart Fail"},{"key":"42592_CR33","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.yjmcc.2014.11.017","volume":"79","author":"JD Clarke","year":"2015","unstructured":"Clarke, J. D. et al. Perturbed atrial calcium handling in an ovine model of heart failure: Potential roles for reductions in the L-type calcium current. J Mol Cell Cardiol 79, 169\u2013179, https:\/\/doi.org\/10.1016\/j.yjmcc.2014.11.017 (2015).","journal-title":"J Mol Cell Cardiol"},{"key":"42592_CR34","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.yjmcc.2012.03.011","volume":"53","author":"MA Horn","year":"2012","unstructured":"Horn, M. A. et al. Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: Collagen accumulation in the young and loss in the aged. Journal of Molecular and Cellular Cardiology 53, 82\u201390, https:\/\/doi.org\/10.1016\/j.yjmcc.2012.03.011 (2012).","journal-title":"Journal of Molecular and Cellular Cardiology"},{"key":"42592_CR35","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1093\/oxfordjournals.eurheartj.a015139","volume":"18","author":"C Coletta","year":"1997","unstructured":"Coletta, C. et al. Prognostic value of left ventricular volume response during dobutamine stress echocardiography. Eur Heart J 18, 1599\u20131605 (1997).","journal-title":"Eur Heart J"},{"key":"42592_CR36","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1111\/j.1365-2125.2005.02553.x","volume":"61","author":"ST Forgue","year":"2006","unstructured":"Forgue, S. T. et al. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol 61, 280\u2013288, https:\/\/doi.org\/10.1111\/j.1365-2125.2005.02553.x (2006).","journal-title":"Br J Clin Pharmacol"},{"key":"42592_CR37","doi-asserted-by":"publisher","first-page":"e003277","DOI":"10.1161\/JAHA.116.003277","volume":"5","author":"JA Hiemstra","year":"2016","unstructured":"Hiemstra, J. A. et al. Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine. J Am Heart Assoc 5, e003277, https:\/\/doi.org\/10.1161\/JAHA.116.003277 (2016).","journal-title":"J Am Heart Assoc"},{"key":"42592_CR38","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1161\/ATVBAHA.108.165043","volume":"28","author":"Z Zhou","year":"2008","unstructured":"Zhou, Z. et al. Protein kinase G phosphorylates soluble guanylyl cyclase on serine 64 and inhibits its activity. Arterioscler Thromb Vasc Biol 28, 1803\u20131810, https:\/\/doi.org\/10.1161\/ATVBAHA.108.165043 (2008).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"42592_CR39","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1161\/CIRCRESAHA.109.212324","volume":"107","author":"S Wei","year":"2010","unstructured":"Wei, S. et al. T-Tubule Remodeling During Transition From Hypertrophy to Heart Failure. Circ Res 107, 521\u2013531, https:\/\/doi.org\/10.1161\/CIRCRESAHA.109.212324 (2010).","journal-title":"Circ Res"},{"key":"42592_CR40","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.hrthm.2011.11.055","volume":"9","author":"T-T Hong","year":"2012","unstructured":"Hong, T.-T. et al. BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart Rhythm 9, 812\u2013820, https:\/\/doi.org\/10.1016\/j.hrthm.2011.11.055 (2012).","journal-title":"Heart Rhythm"},{"key":"42592_CR41","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/nm.3543","volume":"20","author":"T Hong","year":"2014","unstructured":"Hong, T. et al. Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Nature Medicine 20, 624\u2013632, https:\/\/doi.org\/10.1038\/nm.3543 (2014).","journal-title":"Nature Medicine"},{"issue":"Suppl 1","key":"42592_CR42","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1038\/sj.ijir.3901208","volume":"16","author":"E Bischoff","year":"2004","unstructured":"Bischoff, E. Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Int J Impot Res 16(Suppl 1), S11\u201314, https:\/\/doi.org\/10.1038\/sj.ijir.3901208 (2004).","journal-title":"Int J Impot Res"},{"key":"42592_CR43","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1167\/iovs.05-0257","volume":"46","author":"X Zhang","year":"2005","unstructured":"Zhang, X., Feng, Q. & Cote, R. H. Efficacy and selectivity of phosphodiesterase-targeted drugs in inhibiting photoreceptor phosphodiesterase (PDE6) in retinal photoreceptors. Invest Ophthalmol Vis Sci 46, 3060\u20133066, https:\/\/doi.org\/10.1167\/iovs.05-0257 (2005).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"42592_CR44","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1111\/j.1742-1241.2006.01049.x","volume":"60","author":"PJ Wright","year":"2006","unstructured":"Wright, P. J. Comparison of phosphodiesterase type 5 (PDE5) inhibitors. Int J Clin Pract 60, 967\u2013975, https:\/\/doi.org\/10.1111\/j.1742-1241.2006.01049.x (2006).","journal-title":"Int J Clin Pract"},{"key":"42592_CR45","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/sj.ijir.3901283","volume":"17","author":"JL Weeks","year":"2005","unstructured":"Weeks, J. L. et al. High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients. Int J Impot Res 17, 5\u20139, https:\/\/doi.org\/10.1038\/sj.ijir.3901283 (2005).","journal-title":"Int J Impot Res"},{"key":"42592_CR46","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/sj.ijir.3901317","volume":"17","author":"K Loughney","year":"2005","unstructured":"Loughney, K., Taylor, J. & Florio, V. A. 3\u2019,5\u2019-cyclic nucleotide phosphodiesterase 11A: localization in human tissues. Int J Impot Res 17, 320\u2013325, https:\/\/doi.org\/10.1038\/sj.ijir.3901317 (2005).","journal-title":"Int J Impot Res"},{"key":"42592_CR47","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/sj.ijir.3901522","volume":"19","author":"N Mehrotra","year":"2007","unstructured":"Mehrotra, N., Gupta, M., Kovar, A. & Meibohm, B. The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy. Int J Impot Res 19, 253\u2013264, https:\/\/doi.org\/10.1038\/sj.ijir.3901522 (2007).","journal-title":"Int J Impot Res"},{"key":"42592_CR48","doi-asserted-by":"publisher","first-page":"H2272","DOI":"10.1152\/ajpheart.00654.2010","volume":"300","author":"VQ Chau","year":"2011","unstructured":"Chau, V. Q., Salloum, F. N., Hoke, N. N., Abbate, A. & Kukreja, R. C. Mitigation of the progression of heart failure with sildenafil involves inhibition of RhoA\/Rho-kinase pathway. Am J Physiol Heart Circ Physiol 300, H2272\u20132279, https:\/\/doi.org\/10.1152\/ajpheart.00654.2010 (2011).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"42592_CR49","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1007\/s00395-012-0308-y","volume":"107","author":"D Westermann","year":"2012","unstructured":"Westermann, D. et al. Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo. Basic Res Cardiol 107, 308, https:\/\/doi.org\/10.1007\/s00395-012-0308-y (2012).","journal-title":"Basic Res Cardiol"},{"key":"42592_CR50","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1161\/01.RES.0000250046.69918.d5","volume":"99","author":"VO Nikolaev","year":"2006","unstructured":"Nikolaev, V. O., B\u00fcnemann, M., Schmitteckert, E., Lohse, M. J. & Engelhardt, S. Cyclic AMP imaging in adult cardiac myocytes reveals far-reaching \u03b21-adrenergic but locally confined \u03b22-adrenergic receptor-mediated signaling. Circ Res 99, 1084\u20131091, https:\/\/doi.org\/10.1161\/01.RES.0000250046.69918.d5 (2006).","journal-title":"Circ Res"},{"key":"42592_CR51","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.jtcvs.2011.08.048","volume":"143","author":"MG Katz","year":"2012","unstructured":"Katz, M. G. et al. AAV6-\u03b2ARKct gene delivery mediated by molecular cardiac surgery with recirculating delivery (MCARD) in sheep results in robust gene expression and increased adrenergic reserve. J Thorac Cardiovasc Surg 143, 720\u2013726.e723, https:\/\/doi.org\/10.1016\/j.jtcvs.2011.08.048 (2012).","journal-title":"J Thorac Cardiovasc Surg"},{"key":"42592_CR52","doi-asserted-by":"publisher","first-page":"4124","DOI":"10.1128\/MCB.22.12.4124-4135.2002","volume":"22","author":"AN Carr","year":"2002","unstructured":"Carr, A. N. et al. Type 1 phosphatase, a negative regulator of cardiac function. Mol Cell Biol 22, 4124\u20134135 (2002).","journal-title":"Mol Cell Biol"},{"key":"42592_CR53","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10974-011-9261-x","volume":"32","author":"PJ Wijnker","year":"2011","unstructured":"Wijnker, P. J. et al. Protein phosphatase 2A affects myofilament contractility in non-failing but not in failing human myocardium. J Muscle Res Cell Motil 32, 221\u2013233, https:\/\/doi.org\/10.1007\/s10974-011-9261-x (2011).","journal-title":"J Muscle Res Cell Motil"},{"key":"42592_CR54","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fphys.2015.00013","volume":"6","author":"M Lei","year":"2015","unstructured":"Lei, M., Wang, X., Ke, Y. & Solaro, R. J. Regulation of Ca2+ transient by PP2A in normal and failing heart. Front Physiol 6, 13, https:\/\/doi.org\/10.3389\/fphys.2015.00013 (2015).","journal-title":"Front Physiol"},{"issue":"17","key":"42592_CR55","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1161\/CIRCULATIONAHA.116.024470","volume":"135","author":"Thomas Seidel","year":"2017","unstructured":"Seidel, T. et al. Sheet-Like Remodeling of the Transverse Tubular System in Human Heart Failure Impairs Excitation-Contraction Coupling and Functional Recovery by Mechanical Unloading. Circulation, https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.116.024470 (2017).","journal-title":"Circulation"},{"key":"42592_CR56","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1161\/CIRCRESAHA.109.206276","volume":"105","author":"I Lenaerts","year":"2009","unstructured":"Lenaerts, I. et al. Ultrastructural and functional remodeling of the coupling between Ca2+ influx and sarcoplasmic reticulum Ca2+ release in right atrial myocytes from experimental persistent atrial fibrillation. Circ Res 105, 876\u2013885, https:\/\/doi.org\/10.1161\/CIRCRESAHA.109.206276 (2009).","journal-title":"Circ Res"},{"key":"42592_CR57","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1161\/CIRCRESAHA.112.274530","volume":"111","author":"E Wagner","year":"2012","unstructured":"Wagner, E. et al. Stimulated emission depletion live-cell super-resolution imaging shows proliferative remodeling of T-tubule membrane structures after myocardial infarction. Circ Res 111, 402\u2013414, https:\/\/doi.org\/10.1161\/CIRCRESAHA.112.274530 (2012).","journal-title":"Circ Res"},{"key":"42592_CR58","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/cvr\/cvw111","volume":"112","author":"M Frisk","year":"2016","unstructured":"Frisk, M. et al. Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis. Cardiovasc Res 112, 443\u2013451, https:\/\/doi.org\/10.1093\/cvr\/cvw111 (2016).","journal-title":"Cardiovasc Res"},{"key":"42592_CR59","doi-asserted-by":"publisher","first-page":"L53","DOI":"10.1016\/j.bpj.2011.03.046","volume":"100","author":"TG McNary","year":"2011","unstructured":"McNary, T. G., Bridge, J. H. & Sachse, F. B. Strain transfer in ventricular cardiomyocytes to their transverse tubular system revealed by scanning confocal microscopy. Biophys J 100, L53\u201355, https:\/\/doi.org\/10.1016\/j.bpj.2011.03.046 (2011).","journal-title":"Biophys J"},{"key":"42592_CR60","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1161\/CIRCHEARTFAILURE.115.002352","volume":"8","author":"H Li","year":"2015","unstructured":"Li, H. et al. Cardiac Resynchronization Therapy Reduces Subcellular Heterogeneity of Ryanodine Receptors, T-Tubules, and Ca2+ Sparks Produced by Dyssynchronous Heart Failure. Circ Heart Fail 8, 1105\u20131114, https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.115.002352 (2015).","journal-title":"Circ Heart Fail"},{"key":"42592_CR61","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1161\/CIRCHEARTFAILURE.111.964692","volume":"5","author":"AR Lyon","year":"2012","unstructured":"Lyon, A. R. et al. Plasticity of Surface Structures and \u03b22-Adrenergic Receptor Localization in Failing Ventricular Cardiomyocytes During Recovery from Heart Failure. Circ Heart Fail 5, 357\u2013365, https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.111.964692 (2012).","journal-title":"Circ Heart Fail"},{"key":"42592_CR62","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1093\/eurjhf\/hfs038","volume":"14","author":"M Ibrahim","year":"2012","unstructured":"Ibrahim, M. et al. Mechanical unloading reverses transverse tubule remodelling and normalizes local Ca2+-induced Ca2+release in a rodent model of heart failure. Eur J Heart Fail 14, 571\u2013580, https:\/\/doi.org\/10.1093\/eurjhf\/hfs038 (2012).","journal-title":"Eur J Heart Fail"},{"key":"42592_CR63","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1098\/rspb.2011.0624","volume":"278","author":"M Ibrahim","year":"2011","unstructured":"Ibrahim, M., Gorelik, J., Yacoub, M. H. & Terracciano, C. M. The structure and function of cardiac t-tubules in health and disease. Proc Biol Sci 278, 2714\u20132723, https:\/\/doi.org\/10.1098\/rspb.2011.0624 (2011).","journal-title":"Proc Biol Sci"},{"key":"42592_CR64","doi-asserted-by":"publisher","first-page":"e1000372","DOI":"10.1371\/journal.pgen.1000372","volume":"5","author":"JJ Dowling","year":"2009","unstructured":"Dowling, J. J. et al. Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy. PLoS Genet 5, e1000372, https:\/\/doi.org\/10.1371\/journal.pgen.1000372 (2009).","journal-title":"PLoS Genet"},{"key":"42592_CR65","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-1-26","volume":"1","author":"L Al-Qusairi","year":"2011","unstructured":"Al-Qusairi, L. & Laporte, J. T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases. Skelet Muscle 1, 26, https:\/\/doi.org\/10.1186\/2044-5040-1-26 (2011).","journal-title":"Skelet Muscle"},{"key":"42592_CR66","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.1101\/gad.207801","volume":"15","author":"A Razzaq","year":"2001","unstructured":"Razzaq, A. et al. Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila. Genes Dev 15, 2967\u20132979, https:\/\/doi.org\/10.1101\/gad.207801 (2001).","journal-title":"Genes Dev"},{"key":"42592_CR67","doi-asserted-by":"publisher","first-page":"e1000312","DOI":"10.1371\/journal.pbio.1000312","volume":"8","author":"T-T Hong","year":"2010","unstructured":"Hong, T.-T. et al. BIN1 localizes the L-type calcium channel to cardiac T-tubules. PLoS Biol 8, e1000312, https:\/\/doi.org\/10.1371\/journal.pbio.1000312 (2010).","journal-title":"PLoS Biol"},{"key":"42592_CR68","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/stem.2927","volume":"37","author":"DL Mata","year":"2019","unstructured":"Mata, D. L. A. et al. BIN1 Induces the Formation of T-Tubules and Adult-Like Ca2+ Release Units in Developing Cardiomyocytes. Stem Cells 37, 54\u201364, https:\/\/doi.org\/10.1002\/stem.2927 (2019).","journal-title":"Stem Cells"},{"key":"42592_CR69","doi-asserted-by":"publisher","first-page":"31453","DOI":"10.1074\/jbc.272.50.31453","volume":"272","author":"R Wechsler-Reya","year":"1997","unstructured":"Wechsler-Reya, R., Sakamuro, D., Zhang, J., Duhadaway, J. & Prendergast, G. C. Structural analysis of the human BIN1 gene. Evidence for tissue-specific transcriptional regulation and alternate RNA splicing. J Biol Chem 272, 31453\u201331458 (1997).","journal-title":"J Biol Chem"},{"key":"42592_CR70","doi-asserted-by":"publisher","first-page":"H1996","DOI":"10.1152\/ajpheart.00284.2011","volume":"301","author":"MA Richards","year":"2011","unstructured":"Richards, M. A. et al. Transverse (t-) tubules are a common feature in large mammalian atrial myocytes including human. Am J Physiol Heart Circ Physiol 301, H1996\u20132005, https:\/\/doi.org\/10.1152\/ajpheart.00284.2011 (2011).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"42592_CR71","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.ajhg.2014.07.004","volume":"95","author":"PB Agrawal","year":"2014","unstructured":"Agrawal, P. B. et al. SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet 95, 218\u2013226, https:\/\/doi.org\/10.1016\/j.ajhg.2014.07.004 (2014).","journal-title":"Am J Hum Genet"},{"key":"42592_CR72","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/embor.2013.119","volume":"14","author":"B Royer","year":"2013","unstructured":"Royer, B. et al. The myotubularin-amphiphysin 2 complex in membrane tubulation and centronuclear myopathies. EMBO Rep 14, 907\u2013915, https:\/\/doi.org\/10.1038\/embor.2013.119 (2013).","journal-title":"EMBO Rep"},{"key":"42592_CR73","doi-asserted-by":"publisher","first-page":"14432","DOI":"10.1073\/pnas.1604099113","volume":"113","author":"C Kutchukian","year":"2016","unstructured":"Kutchukian, C. et al. Phosphatidylinositol 3-kinase inhibition restores Ca2+ release defects and prolongs survival in myotubularin-deficient mice. Proc Natl Acad Sci USA 113, 14432\u201314437, https:\/\/doi.org\/10.1073\/pnas.1604099113 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"42592_CR74","doi-asserted-by":"publisher","first-page":"18763","DOI":"10.1073\/pnas.0900705106","volume":"106","author":"L Al-Qusairi","year":"2009","unstructured":"Al-Qusairi, L. et al. T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase. Proc Natl Acad Sci USA 106, 18763\u201318768, https:\/\/doi.org\/10.1073\/pnas.0900705106 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"42592_CR75","doi-asserted-by":"publisher","first-page":"e1000412","DOI":"10.1371\/journal.pbio.1000412","volume":"8","author":"C Kilkenny","year":"2010","unstructured":"Kilkenny, C., Browne, W. J., Cuthill, I. C., Emerson, M. & Altman, D. G. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8, e1000412, https:\/\/doi.org\/10.1371\/journal.pbio.1000412 (2010).","journal-title":"PLoS Biol"},{"key":"42592_CR76","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1161\/CIRCRESAHA.113.301348","volume":"113","author":"C Pinali","year":"2013","unstructured":"Pinali, C., Bennett, H., Davenport, J. B., Trafford, A. W. & Kitmitto, A. 3-D Reconstruction of the Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking T-Tubules: This Organization is Perturbed in Heart Failure. Circ Res 113, 1219\u20131230, https:\/\/doi.org\/10.1161\/CIRCRESAHA.113.301348 (2013).","journal-title":"Circ Res"},{"key":"42592_CR77","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1093\/cvr\/cvu158","volume":"103","author":"DJ Greensmith","year":"2014","unstructured":"Greensmith, D. J., Galli, G. L. J., Trafford, A. W. & Eisner, D. A. Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions. Cardiovasc Res 103, 554\u2013563, https:\/\/doi.org\/10.1093\/cvr\/cvu158 (2014).","journal-title":"Cardiovasc Res"},{"key":"42592_CR78","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/BF00374521","volume":"425","author":"AW Trafford","year":"1993","unstructured":"Trafford, A. W., O\u2019Neill, S. C. & Eisner, D. A. Factors affecting the propagation of locally activated systolic Ca transients in rat ventricular myocytes. Pflugers Arch 425, 181\u2013183 (1993).","journal-title":"Pflugers Arch"},{"key":"42592_CR79","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.yjmcc.2008.11.003","volume":"46","author":"AP Walden","year":"2009","unstructured":"Walden, A. P., Dibb, K. M. & Trafford, A. W. Differences in intracellular calcium homeostasis between atrial and ventricular myocytes. J Mol Cell Cardiol 46, 463\u2013473, https:\/\/doi.org\/10.1016\/j.yjmcc.2008.11.003 (2009).","journal-title":"J Mol Cell Cardiol"},{"key":"42592_CR80","doi-asserted-by":"publisher","first-page":"21","DOI":"10.12793\/tcp.2017.25.1.21","volume":"25","author":"K-Y Kim","year":"2017","unstructured":"Kim, K.-Y. et al. Validated UPLC-MS\/MS method for the determination of tadalafil in human plasma and its application to a pharmacokinetic study. Translational and Clinical Pharmacology 25, 21\u201327, https:\/\/doi.org\/10.12793\/tcp.2017.25.1.21 (2017).","journal-title":"Translational and Clinical Pharmacology"},{"key":"42592_CR81","doi-asserted-by":"publisher","first-page":"e0201910","DOI":"10.1371\/journal.pone.0201910","volume":"13","author":"L Clasen","year":"2018","unstructured":"Clasen, L. et al. A modified approach for programmed electrical stimulation in mice: Inducibility of ventricular arrhythmias. PLoS One 13, e0201910, https:\/\/doi.org\/10.1371\/journal.pone.0201910 (2018).","journal-title":"PLoS One"},{"key":"42592_CR82","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/sim.4780140810","volume":"14","author":"ON Keene","year":"1995","unstructured":"Keene, O. N. The log transformation is special. Stat Med 14, 811\u2013819 (1995).","journal-title":"Stat Med"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42592-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42592-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42592-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T04:07:19Z","timestamp":1671250039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42592-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,1]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["42592"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-42592-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/248187","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,1]]},"assertion":[{"value":"29 December 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6801"}}