{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T02:57:26Z","timestamp":1718765846063},"reference-count":20,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:p> Recently, we reported that exogenous administration of Met<jats:sup>5<\/jats:sup>-enkephalin (ME) for 24 h reduces infarct size after ischemia-reperfusion in rabbits. In the present study, we tested whether ME-induced cardioprotection is exhibited in murine hearts and whether chronic infusion of this peptide can render hearts tolerant to ischemia. Barbiturate-anesthetized open-chest mice (C57BL\/6J) were subjected to regional myocardial ischemia-reperfusion (45 min of occlusion and 20 min of reperfusion). Mice received saline vehicle or ME for 24 h or 2 wk before undergoing regional myocardial ischemia-reperfusion or for 24 h followed by a 24-h delay before regional myocardial ischemia-reperfusion. Infarct size was measured with propidium iodide and is expressed as a percentage of the area at risk. Infarcts were smaller after infusion of ME for 24 h than with vehicle control: 49.2 \u00b1 9.0% vs. 22.2 \u00b1 3.2% ( P &lt; 0.01). In contrast, administration of ME for 2 wk failed to elicit cardioprotection: 36.5 \u00b1 9.1% and 41.4 \u00b1 8.2% for control and ME, respectively ( P = not significant). When a 24-h delay was imposed between the end of drug treatment and the onset of the ischemic insult, cardioprotection was lost: 38.5 \u00b1 6.1% and 42.8 \u00b1 6.6% for control and ME, respectively ( P = not significant). Chronic sustained exogenous infusion of the endogenously produced opioid peptide ME is associated with loss of the cardioprotection that is observed with 24 h of infusion. Furthermore, in this in vivo murine model, ME failed to induce delayed tolerance to myocardial ischemia-reperfusion. <\/jats:p>","DOI":"10.1152\/ajpheart.00257.2004","type":"journal-article","created":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T20:24:14Z","timestamp":1100809454000},"page":"H1717-H1723","source":"Crossref","is-referenced-by-count":8,"title":["Long-term infusion of Met<sup>5<\/sup>-enkephalin fails to protect murine hearts against ischemia-reperfusion injury"],"prefix":"10.1152","volume":"288","author":[{"given":"Koh","family":"Kuzume","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyo","family":"Kuzume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiping","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M.","family":"Van Winkle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P. 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