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Eight groups of pigs (total <jats:italic>n<\/jats:italic>\u2009=\u2009122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60\u00a0min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75\u00a0mg\/kg) or vehicle (saline) 20\u00a0min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, <jats:italic>p<\/jats:italic>\u2009=\u20090.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was \u2248\u20095% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35\u00a0min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (<jats:italic>p<\/jats:italic>\u2009=\u20090.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50\u00a0min had smaller infarcts than control pigs undergoing ischemia for 40 or 45\u00a0min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, <jats:italic>p<\/jats:italic>\u2009=\u20090.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.<\/jats:p>","DOI":"10.1007\/s00395-020-0812-4","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T17:05:52Z","timestamp":1596474352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Metoprolol blunts the time-dependent progression of infarct size"],"prefix":"10.1007","volume":"115","author":[{"given":"Manuel","family":"Lobo-Gonzalez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Gal\u00e1n-Arriola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Rossello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maribel","family":"Gonz\u00e1lez\u2010Del\u2010Hoyo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Paul","family":"Vilchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda I.","family":"Higuero-Verdejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose M.","family":"Garc\u00eda-Ruiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo J.","family":"L\u00f3pez-Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"S\u00e1nchez-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Pizarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Fuster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5036-254X","authenticated-orcid":false,"given":"Borja","family":"Ibanez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"812_CR1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00395-018-0696-8","volume":"113","author":"HE Botker","year":"2018","unstructured":"Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. 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