Editing Thrombosis (section)

=== Targeting ischemia/reperfusion injury ===
{{Main|Reperfusion injury}}
With reperfusion comes ischemia/reperfusion (IR) injury (IRI), which paradoxically causes cell death in reperfused tissue<ref name="Grace 637–647">{{Cite journal|last=Grace|first=P. A.|date=May 1994|title=Ischaemia-reperfusion injury|journal=The British Journal of Surgery|volume=81|issue=5|pages=637–647|issn=0007-1323|pmid=8044536|doi=10.1002/bjs.1800810504|s2cid=34608929}}</ref> and contributes significantly to post-reperfusion mortality and morbidity.<ref>{{Cite journal|last1=Yellon|first1=Derek M.|author1-link=Derek M. Yellon|last2=Hausenloy|first2=Derek J.|date=September 13, 2007|title=Myocardial Reperfusion Injury|journal=New England Journal of Medicine|volume=357|issue=11|pages=1121–1135|doi=10.1056/nejmra071667|pmid=17855673|issn=0028-4793}}</ref><ref>{{Cite journal|last1=Bai|first1=Jilin|last2=Lyden|first2=Patrick D.|date=January 19, 2015|title=Revisiting Cerebral Postischemic Reperfusion Injury: New Insights in Understanding Reperfusion Failure, Hemorrhage, and Edema|journal=International Journal of Stroke|volume=10|issue=2|pages=143–152|doi=10.1111/ijs.12434|pmid=25598025|s2cid=25953179|issn=1747-4930}}</ref> For example, in a feline model of intestinal ischemia, four hours of ischemia resulted in less injury than three hours of ischemia followed by one hour of reperfusion.<ref name="Grace 637–647"/> In ST-elevation myocardial infarction (STEMI), IRI contributes up to 50% of final infarct size despite timely primary percutaneous coronary intervention. This is a key reason for the continued high mortality and morbidity in these conditions, despite endovascular reperfusion treatments and continuous efforts to improve timeliness and access to these treatments. Hence, protective therapies are required to attenuate IRI alongside reperfusion in acute ischemic conditions to improve clinical outcomes.<ref name="Ho 1">{{Cite journal|last1=Ho|first1=Andrew Fu Wah|last2=Jun|first2=Chong|last3=Ong|first3=Marcus Eng Hock|last4=Hausenloy|first4=Derek J.|date=April 2019|title=Remote Ischemic Conditioning in Emergency Medicine—Clinical Frontiers and Research Opportunities|journal=SHOCK|volume=53|issue=3|pages=269–276|doi=10.1097/SHK.0000000000001362|pmid=32045394|s2cid=149537443|issn=1073-2322|url=https://discovery.ucl.ac.uk/id/eprint/10093574/1/Hausenloy_Manuscript%2023%20Mar%202019%20accepted%20version.pdf}}</ref> Therapeutic strategies that have potential to improve clinical outcomes in reperfused STEMI patients include [[remote ischemic conditioning]] (RIC), exenatide, and metoprolol. These have emerged amongst a multitude of cardioprotective interventions investigated with largely neutral clinical data.<ref>{{Cite journal|last1=Hausenloy|first1=Derek J.|last2=Botker|first2=Hans Erik|last3=Engstrom|first3=Thomas|last4=Erlinge|first4=David|last5=Heusch|first5=Gerd|last6=Ibanez|first6=Borja|last7=Kloner|first7=Robert A.|last8=Ovize|first8=Michel|last9=Yellon|first9=Derek M.|date=April 26, 2016|title=Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations|journal=European Heart Journal|volume=38|issue=13|pages=935–941|doi=10.1093/eurheartj/ehw145|pmid=27118196|issn=0195-668X|pmc=5381598}}</ref> Of these, RIC has the most robust clinical evidence, especially in the context of STEMI, but also emerging for other indications such as acute ischemic stroke and aneurysmal subarachnoid hemorrhage.<ref name="Ho 1"/>