{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:55:44Z","timestamp":1788051344189,"version":"build-2784847793"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T00:00:00Z","timestamp":1494547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Summary<\/jats:title>\n \n Aims<\/jats:title>\n \n Exposure of the heart to 5 min global ischaemia (I) followed by 5 min reperfusion (R) (ischaemic preconditioning,\n IPC<\/jats:styled-content>\n ) or transient Beta 2\u2010adrenergic receptor (B2\u2010\n AR<\/jats:styled-content>\n ) stimulation with formoterol (B2\n PC<\/jats:styled-content>\n ), followed by 5 min washout before index ischaemia, elicits cardioprotection against subsequent sustained ischaemia. As the washout period during preconditioning is essential for subsequent cardioprotection, the aim of this study was to investigate the involvement of protein kinase A (\n PKA<\/jats:styled-content>\n ), reactive oxygen species (\n ROS<\/jats:styled-content>\n ), extracellular signal\u2010regulated kinase (\n ERK<\/jats:styled-content>\n ),\n PKB<\/jats:styled-content>\n \/Akt, p38\n MAPK<\/jats:styled-content>\n and c\u2010jun N\u2010terminal kinase (\n JNK<\/jats:styled-content>\n ) during this period.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Isolated perfused rat hearts were exposed to\n IPC<\/jats:styled-content>\n (1x5min I \/ 5min R) or B2\n PC<\/jats:styled-content>\n (1x5min Formoterol \/ 5min R) followed by 35 min regional ischaemia and reperfusion. Inhibitors for\n PKA<\/jats:styled-content>\n (Rp\u20108\n CPT<\/jats:styled-content>\n \u2010\n cAMP<\/jats:styled-content>\n )(16\u03bcM),\n ROS<\/jats:styled-content>\n (\n NAC<\/jats:styled-content>\n )(300\u03bcM),\n PKB<\/jats:styled-content>\n (A\u20106730)(2.5\u03bcM),\n ERK<\/jats:styled-content>\n p44\/p42 (\n PD<\/jats:styled-content>\n 98,059)(10\u03bcM), p38\n MAPK<\/jats:styled-content>\n (\n SB<\/jats:styled-content>\n 239063)(1\u03bcM) or\n JNK<\/jats:styled-content>\n (\n SP<\/jats:styled-content>\n 600125)(10\u03bcM) were administered for 5 minutes before 5 minutes global ischaemia \/ 5 min reperfusion (\n IPC<\/jats:styled-content>\n ) or for 5 minutes before and during administration of formoterol (B2\n PC<\/jats:styled-content>\n ) prior to regional ischaemia, reperfusion and infarct size (\n IS<\/jats:styled-content>\n ) determination. Hearts exposed to B2\n PC<\/jats:styled-content>\n or\n IPC<\/jats:styled-content>\n were freeze\u2010clamped during the washout period for Western blots analysis of\n PKB<\/jats:styled-content>\n ,\n ERK<\/jats:styled-content>\n p44\/p42, p38\n MAPK<\/jats:styled-content>\n and\n JNK<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n PKA<\/jats:styled-content>\n blocker abolished both B2\n PC<\/jats:styled-content>\n and\n IPC<\/jats:styled-content>\n , while\n NAC<\/jats:styled-content>\n significantly increased\n IS<\/jats:styled-content>\n of\n IPC<\/jats:styled-content>\n but not of B2\n PC<\/jats:styled-content>\n . Western blot analysis showed that\n ERK<\/jats:styled-content>\n p44\/p42 and\n PKB<\/jats:styled-content>\n activation during washout after B2\n PC<\/jats:styled-content>\n compared to\n IPC<\/jats:styled-content>\n was significantly increased.\n IPC<\/jats:styled-content>\n compared to B2\n PC<\/jats:styled-content>\n showed significant p38\n MAPK<\/jats:styled-content>\n and\n JNK<\/jats:styled-content>\n p54\/p46 activation.\n PKB<\/jats:styled-content>\n and\n ERK<\/jats:styled-content>\n inhibition or p38\n MAPK<\/jats:styled-content>\n and\n JNK<\/jats:styled-content>\n inhibition during the washout period of B2\n PC<\/jats:styled-content>\n and\n IPC<\/jats:styled-content>\n respectively, significantly increased\n IS<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n PKA<\/jats:styled-content>\n activation before regional ischaemia is a prerequisite for cardioprotection in both B2\n PC<\/jats:styled-content>\n and\n IPC<\/jats:styled-content>\n . However,\n ROS<\/jats:styled-content>\n was crucial only in\n IPC<\/jats:styled-content>\n . Kinase activation during the washout phase of\n IPC<\/jats:styled-content>\n and B2\n PC<\/jats:styled-content>\n , albeit different, affords the same cardioprotective response.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1755-5922.12252","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T16:16:57Z","timestamp":1485274617000},"source":"Crossref","is-referenced-by-count":5,"title":["The significance of the washout period in preconditioning"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-4025","authenticated-orcid":false,"given":"Ruduwaan","family":"Salie","sequence":"first","affiliation":[{"name":"Biomedical Research and Innovation Platform South African Medical Research Council Parow Valley Cape Town South Africa"},{"name":"Faculty of Medicine and Health Sciences Division of Medical Physiology University of Stellenbosch Tygerberg Cape Town South 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