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Timely reperfusion reduces infarct size and mortality. The history of reperfusion therapy from the first clinical use of intravenous streptokinase in patients with acute myocardial infarction by Sherry et al. in the late 1950s, over seminal experimental dog studies by Ross Jr. et al., demonstrating infarct size reduction by timely reperfusion in the early 1970s, to a more systematic use of initially streptokinase and a later tissue plasminogen activator in clinical trials (GISSI, TIMI), the addition of platelet inhibition (ISIS) and ultimately mechanical recanalization by percutaneous coronary intervention with stenting, is reviewed in detail. Cardioprotection beyond timely reperfusion was first demonstrated in the seminal experimental dog studies of ischemic conditioning by Murry, Reimer, and Jennings in the 1980s and initiated a tsunami of experimental studies in various experimental models to identify the underlying signal transduction, but has not yet been established in clinical practice. Clinical trials on various forms of ischemic conditioning, potentially cardioprotective drugs and transcutaneous vagal nerve stimulation, are still underway.<\/jats:p>","DOI":"10.1007\/s00395-026-01198-1","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:11:57Z","timestamp":1784304717000},"page":"817-825","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Historical account of reperfusion therapy and the development of cardioprotection beyond reperfusion"],"prefix":"10.1007","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-4160","authenticated-orcid":false,"given":"Gerd","family":"Heusch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Kleinbongard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard J.","family":"Gersh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"1198_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-018-0696-8","volume":"113","author":"HE B\u00f8tker","year":"2018","unstructured":"B\u00f8tker 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, Schl\u00fcter 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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