{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:20:33Z","timestamp":1790644833400,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The kynurenine pathway (\n              <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n              ) is the major route of tryptophan (\n              <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>\n              ) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the\n              <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n              activation level correlates with severity of post\u2013cardiac arrest shock, early death, and long\u2010term outcome.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24\u00a0hours were collected. A cerebral performance category of 3 to 5 defined 12\u2010month poor outcome. Plasma\n              <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>\n              and\n              <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n              metabolites, kynurenine (\n              <jats:styled-content style=\"fixed-case\">KYN<\/jats:styled-content>\n              ), kynurenic acid, 3\u2010hydroxyanthranilic acid, and the ratio of\n              <jats:styled-content style=\"fixed-case\">KYN<\/jats:styled-content>\n              to\n              <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>\n              were measured by liquid chromatography and mass spectrometry. All\n              <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n              metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and\n              <jats:styled-content style=\"fixed-case\">kynurenic acid<\/jats:styled-content>\n              and 3\u2010hydroxyanthranilic acid correlated with time to\n              <jats:styled-content style=\"fixed-case\">return of spontaneous circulation<\/jats:styled-content>\n              . Patients with higher levels of\n              <jats:styled-content style=\"fixed-case\">KYN<\/jats:styled-content>\n              ,\n              <jats:styled-content style=\"fixed-case\">KYN<\/jats:styled-content>\n              to\n              <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>\n              ,\n              <jats:styled-content style=\"fixed-case\">kynurenic acid<\/jats:styled-content>\n              , and 3\u2010hydroxyanthranilic acid had lower 24\u2010hour systolic arterial pressure and bicarbonate. All\n              <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n              metabolites and the ratio of\n              <jats:styled-content style=\"fixed-case\">KYN<\/jats:styled-content>\n              to\n              <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>\n              , but not\n              <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>\n              , were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high\n              <jats:styled-content style=\"fixed-case\">kynurenic acid<\/jats:styled-content>\n              (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008;\n              <jats:italic>P<\/jats:italic>\n              =0.014), and 3\u2010hydroxyanthranilic acid (\n              <jats:styled-content style=\"fixed-case\">odds ratio:<\/jats:styled-content>\n              1.011; 95% confidence interval: 1.001 to 1.022;\n              <jats:italic>P<\/jats:italic>\n              =0.03) were independently associated with 12\u2010month poor outcome and significantly improved risk reclassification.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>\n              is activated early after cardiac arrest and is associated with severity of post\u2013\n              <jats:styled-content style=\"fixed-case\">cardiac arrest<\/jats:styled-content>\n              shock, early death, and poor long\u2010term outcome.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001094","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T02:01:45Z","timestamp":1407204105000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Early Activation of the Kynurenine Pathway Predicts Early Death and Long\u2010term Outcome in Patients Resuscitated From Out\u2010of\u2010Hospital Cardiac Arrest"],"prefix":"10.1161","volume":"3","author":[{"given":"Giuseppe","family":"Ristagno","sequence":"first","affiliation":[{"name":"IRCCS \u2013 Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d, Milan, 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Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"Varpula","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Lucchetti","sequence":"additional","affiliation":[{"name":"IRCCS \u2013 Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Fracasso","sequence":"additional","affiliation":[{"name":"IRCCS \u2013 Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Guiso","sequence":"additional","affiliation":[{"name":"IRCCS \u2013 Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d, Milan, 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