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Early activation of the kynurenine pathway predicts early death and long-term outcome in patients resuscitated from out-of-hospital cardiac arrest
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نویسنده
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ristagno g. ,latini r. ,vaahersalo j. ,masson s. ,kurola j. ,varpula t. ,lucchetti j. ,fracasso c. ,guiso g. ,montanelli a. ,barlera s. ,gobbi m. ,tiainen m. ,pettilä v. ,skrifvars m.b. ,lund v. ,tuominen p. ,johansson s. ,perkola p. ,kumpulainen e. ,suvela m. ,hirvonen s. ,kauppinen s. ,laru-sompa r. ,reilama m. ,laine h. ,kettunen p. ,smolander i. ,reinikainen m. ,surakka t. ,saarinen k. ,lähdeaho p. ,soini j. ,hovilehto s. ,koivisto s.-p. ,hautamäki r. ,alaspää a. ,heikkilä t. ,kiviniemi o. ,lintula e. ,kaminski t. ,roiko j. ,alila s. ,pentti j. ,koskinen r. ,heikkinen j. ,oksanen t. ,eronen a. ,hult t. ,nieminen t. ,bäcklund t. ,kauhanen l. ,kaukonen k.-m. ,pettilä v. ,pettilä l. ,sutinen s. ,hoppu s. ,tenhunen j. ,karlsson s. ,kukkurainen a. ,varila s. ,kortelainen s. ,peltola m.-l. ,hiltunen p. ,kurola j. ,ruokonen e. ,halonen e. ,rissanen s. ,rahikainen s. ,ahola r. ,ala-kokko t. ,sälkiö s.
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منبع
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journal of the american heart association - 2014 - دوره : 3 - شماره : 4
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چکیده
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Background-the kynurenine pathway (kp) is the major route of tryptophan (trp) catabolism and is activated by inflammation and after cardiac arrest in animals. we hypothesized that the kp activation level correlates with severity of post-cardiac arrest shock,early death,and long-term outcome. methods and results-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 hours were collected. a cerebral performance category of 3 to 5 defined 12-month poor outcome. plasma trp and kp metabolites,kynurenine (kyn),kynurenic acid,3-hydroxyanthranilic acid,and the ratio of kyn to trp were measured by liquid chromatography and mass spectrometry. all kp 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 kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. patients with higher levels of kyn,kyn to trp,kynurenic acid,and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. all kp metabolites and the ratio of kyn to trp,but not trp,were significantly higher in patients who died in the intensive care unit in comparison to those who survived. multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; p=0.014),and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; p=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification. conclusions-kp is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock,early death,and poor long-term outcome. © 2014 the authors.
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کلیدواژه
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Brain; Cardiac arrest; Kynurenine; Shock; Survival; Tryptophan
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آدرس
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irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, department of anesthesiology and intensive care medicine,helsinki university central hospital,helsinki, Finland, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, department of intensive care,kuopio university central hospital,kuopio, Finland, department of anesthesiology and intensive care medicine,helsinki university central hospital,helsinki, Finland, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, clinical investigations laboratory,humanitas clinical and research center,milan, Italy, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, irccs - istituto di ricerche farmacologiche 'mario negri',milan, Italy, department of neurology,helsinki university hospital,helsinki, Finland, department of anesthesiology and intensive care medicine,helsinki university central hospital,helsinki, Finland, department of anesthesiology and intensive care medicine,helsinki university central hospital,helsinki, Finland, satakunta central hospital, Finland, satakunta central hospital, Finland, satakunta central hospital, Finland, satakunta central hospital, Finland, satakunta central hospital, Finland, east savo central hospital, Finland, east savo central hospital, Finland, east savo central hospital, Finland, central finland central hospital, Finland, central finland central hospital, Finland, south savo central hospital, Finland, south savo central hospital, Finland, south savo central hospital, Finland, north carelia central hospital, Finland, north carelia central hospital, Finland, seinäjoki central hospital, Finland, seinäjoki central hospital, Finland, seinäjoki central hospital, Finland, south carelia central hospital, Finland, vaasa central hospital, Finland, vaasa central hospital, Finland, kanta-häme central hospital, Finland, kanta-häme central hospital, Finland, lappi central hospital, Finland, lappi central hospital, Finland, keski-pohjanmaa central hospital, Finland, keski-pohjanmaa central hospital, Finland, kymenlaakso central hospital, Finland, kymenlaakso central hospital, Finland, kymenlaakso central hospital, Finland, länsi- pohja's central hospital, Finland, helsinki university hospital,jorvi hospital, Finland, helsinki university hospital,jorvi hospital, Finland, helsinki university hospital,jorvi hospital, Finland, helsinki university hospital,jorvi hospital, Finland, meilahti hospital medical icu, Finland, meilahti hospital medical icu, Finland, meilahti hospital icu, Finland, meilahti hospital icu, Finland, meilahti hospital icu, Finland, meilahti hospital icu, Finland, tampere university hospital, Finland, tampere university hospital, Finland, tampere university hospital, Finland, tampere university hospital, Finland, tampere university hospital, Finland, tampere university hospital, Finland, tampere university hospital, Finland, kuopio university hospital, Finland, kuopio university hospital, Finland, kuopio university hospital, Finland, kuopio university hospital, Finland, kuopio university hospital, Finland, kuopio university hospital, Finland, oulu university hospital, Finland, oulu university hospital, Finland, oulu university hospital, Finland
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Authors
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