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As a first step toward determining the suitability of this technique, we aimed to (1) characterize the response to microinjuries in the healthy and cirrhotic liver, and (2) determine the underlying cause for any differences in response. Healthy and cirrhotic rats were treated with a fractional laser then euthanized from 0\u2009h up to 14\u2009days after treatment. Differential expression was assessed using RNAseq with a difference\u2010in\u2010differences model. Spatial maps of tissue oxygenation were acquired with hyperspectral imaging and disruptions in blood supply were assessed with tomato lectin perfusion. Healthy rats showed little damage beyond the initial microinjury and healed completely by 7\u2009days without scarring. In cirrhotic rats, hepatocytes surrounding microinjury sites died 4\u20106\u2009h after ablation, resulting in enlarged and heterogeneous zones of cell death. Hepatocytes near blood vessels were spared, particularly near the highly vascularized septa. Gene sets related to ischemia and angiogenesis were enriched at 4\u2009h. Laser\u2010treated regions had reduced oxygen saturation and broadly disrupted perfusion of nodule microvasculature, which matched the zones of cell death. Our results demonstrate that the cirrhotic liver has an exacerbated response to microinjuries and increased susceptibility to ischemia from microvascular damage, likely related to the vascular derangements that occur during cirrhosis development. Modifications to the fractional laser tool, such as using a femtosecond laser or reducing the spot size, may be able to prevent large disruptions of perfusion and enable further development of a laser\u2010induced microinjury treatment for cirrhosis.<\/jats:p>","DOI":"10.1096\/fj.202301438rr","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T07:01:01Z","timestamp":1714028461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased susceptibility to ischemia causes exacerbated response to microinjuries in the cirrhotic liver"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-7472","authenticated-orcid":false,"given":"Ben D.","family":"Leaker","sequence":"first","affiliation":[{"name":"Health Sciences and Technology Harvard\u2010Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-5910","authenticated-orcid":false,"given":"Mozhdeh","family":"Sojoodi","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Oncologic Surgery Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Surgery Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1920-3417","authenticated-orcid":false,"given":"Kenneth K.","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Oncologic Surgery Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Surgery Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-942X","authenticated-orcid":false,"given":"Yury V.","family":"Popov","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Beth Israel Deaconess Medical Center  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-3888","authenticated-orcid":false,"given":"Joshua","family":"Tam","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Dermatology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-3035","authenticated-orcid":false,"given":"R. 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