{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T17:41:42Z","timestamp":1785606102905,"version":"3.56.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":11141,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1985,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Acetaminophen\u2013induced (750 mg per kg p.o.) hepatotoxicity in mice is characterized by hepatomegaly and massive centrilobular congestion which precede the appearance of necrosis. The vascular changes are correlated with the morphologic features using liver hemoglobin content to quantitate erythrocyte sequestration, and hematocrit measurements and <jats:sup>125<\/jats:sup>I\u2013albumin injections to determine plasma and blood volume. The initial increase in liver size was a result of plasma accumulation due to endocytic vacuolation of hepatocytes and Disse space enlargement in centrilobular regions. Further increases in liver size after 3 hr were a consequence of erythrocyte and additional plasma sequestration within the damaged liver. These events occurred without any increase in intrahepatic or portal venous pressure. Hepatic hemoglobin and plasma levels increased 10\u2013 and 5\u2013fold, respectively, by 4.5 to 6 hr after administration of acetaminophen. There are two major consequences of acetaminophen\u2013induced hepatotoxic congestion. First, blood and plasma volumes fell significantly, and we suggest that hypovolemic shock contributes to early mortality after acetaminophen. Second, impaired circulation within the congested liver, as manifested by reduced <jats:sup>125<\/jats:sup>I\u2013albumin entry into the liver when <jats:sup>125<\/jats:sup>I\u2013albumin was injected after congestion had developed, probably aggravates the initial injury. Early lesions were always evenly distributed around central veins. However, the pattern of damage at 24 hr could be variable. Occasional large confluent areas of necrosis were always congested, which is consistent with the concept that secondary ischemic damage can develop. Congestion and hypovolemia are reversible and can be largely prevented by administration of the protective compound <jats:italic toggle=\"yes\">N<\/jats:italic>\u2013acetylcysteine (1,200 mg per kg p.o.) 3 hr after acetaminophen.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840050213","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T17:59:21Z","timestamp":1172944761000},"page":"233-240","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":47,"title":["Acetaminophen\u2013Induced Hepatotoxic Congestion in Mice"],"prefix":"10.1097","volume":"5","author":[{"given":"Robin M.","family":"Walker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Racz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis T.","family":"McElligott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840050213-BIB1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1136\/bmj.2.5512.497","volume":"2","author":"Davidson","year":"1966","journal-title":"Br Med J"},{"key":"10.1002\/hep.1840050213-BIB2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.3.5722.557","volume":"3","author":"Proudfoot","year":"1970","journal-title":"Br Med J"},{"key":"10.1002\/hep.1840050213-BIB3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1001\/archinte.1981.00340030112020","volume":"141","author":"Rumack","year":"1981","journal-title":"Arch Intern Med"},{"key":"10.1002\/hep.1840050213-BIB4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1289\/ehp.761527","volume":"15","author":"Mitchell","year":"1976","journal-title":"Environ Health Perspect"},{"key":"10.1002\/hep.1840050213-BIB5","series-title":"ACS Symposium","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1021\/bk-1977-0044.ch008","volume-title":"Drug Metabolism Concepts","author":"Nelson","year":"1977","unstructured":", . 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