{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:59:34Z","timestamp":1790866774819,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1999,4,16]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Opioids have been previously shown to confer short-term cardioprotection against a prolonged ischemic insult. Therefore, the present study was designed to determine whether opioids can induce a delayed or \u201csecond window\u201d of cardioprotection and to assess the potential involvement of the mitochondrial K\n            <jats:sub>ATP<\/jats:sub>\n            channel. All rats were subjected to 30 minutes of ischemia and 2 hours of reperfusion (I\/R). Control animals, injected with saline 24 hours before I\/R, elicited an infarct size\/area at risk (IS\/AAR) of 62.9\u00b13.4. TAN-67, a \u03b41-opioid receptor agonist, was administered 10 or 30 mg\/kg IP 12, 24, 48, or 72 hours before I\/R. TAN-67 (10 mg\/kg) 12- or 24-hour pretreatment did not significantly reduce IS\/AAR (62.1\u00b16.3 and 43.3\u00b17.3, respectively). Similarly, 12-hour pretreatment with TAN-67 (30 mg\/kg) did not reduce IS\/AAR (60.0\u00b15.6); however, 24-hour pretreatment significantly reduced IS\/AAR (34.5\u00b15.9). Forty-eight\u2013hour pretreatment with TAN-67 maximally reduced IS\/AAR (29.2\u00b17.0), and opioid-induced cardioprotection was lost after 72-hour pretreatment (61.7\u00b13.8). TAN-67\u2013induced cardioprotection could be abolished by pretreatment with the selective \u03b4\n            <jats:sub>1<\/jats:sub>\n            -opioid receptor antagonist 7-benzylidenenaltrexone, BNTX, administered either 30 minutes before TAN-67 given 48 hours before I\/R or 10 minutes before I\/R in rats previously treated for 48 hours with TAN-67 (59.6\u00b13.1 and 58.7\u00b13.5, respectively). The involvement of the K\n            <jats:sub>ATP<\/jats:sub>\n            channel was investigated with 2 inhibitors: glibenclamide, a nonselective K\n            <jats:sub>ATP<\/jats:sub>\n            channel inhibitor, and 5-hydroxydecanoic acid, selective for the mitochondrial K\n            <jats:sub>ATP<\/jats:sub>\n            channel in rabbits. Glibenclamide, administered 30 minutes before I\/R in 48-hour TAN-67\u2013pretreated rats, completely abolished cardioprotection (60.4\u00b13.2). Similarly, 5-hydroxydecanoic acid, administered 5 minutes before I\/R in rats pretreated 48 hours previously with TAN-67, completely abolished cardioprotection (57.8\u00b12.5). These results suggest that \u03b4\n            <jats:sub>1<\/jats:sub>\n            -opioid receptor stimulation, 24 to 48 hours before an ischemic insult, produces a delayed cardioprotective effect that is possibly the result of mitochondrial K\n            <jats:sub>ATP<\/jats:sub>\n            channel activation.\n          <\/jats:p>","DOI":"10.1161\/01.res.84.7.846","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"846-851","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":146,"title":["Opioid-Induced Second Window of Cardioprotection"],"prefix":"10.1161","volume":"84","author":[{"given":"Ryan M.","family":"Fryer","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Hsu","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis T.","family":"Eells","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nagase","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett J.","family":"Gross","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"H2157","volume":"268","year":"1995","unstructured":"Schultz J, Rose E, Yao Z, Gross G. 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