{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:42:46Z","timestamp":1790898166768,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1997,10,1]],"date-time":"1997-10-01T00:00:00Z","timestamp":875664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diaspirin crosslinked hemoglobin (DCLHb) is a cell-free hemoglobin derived from human erythrocytes. DCLHb has been shown to improve blood flow to vital organs in healthy and septic animals. In this study, we determined the efficacy of DCLHb by comparing its effect on systemic O2 uptake to freshly stored and aged red blood cells (RBCs) in septic rats. Twenty-four hours after induction of sepsis by cecal ligation and perforation, O2 supply dependency was created by isovolemic hemodilution with rat plasma. In O2 supply dependency, rats were randomized to receive an exchange transfusion of 7.5 ml \u201cfresh\u201d RBCs (stored &amp;lt; 6 d; Hct: 70%), \u201cfresh\u201d diluted RBCs (stored &amp;lt; 6 d; Hct: 30%), \u201cold\u201d RBCs (stored 28 to 35 d; Hct: 70%), or DCLHb (Hb: 100 g\/L). We found, that survival following O2 supply dependency and transfusion with old RBCs was poor (33% versus 91.7% in the other groups; p &amp;lt; 0.01), precluding further analysis of post-transfusion data from this group. Systemic O2 uptake increased in all remaining groups (p &amp;lt; 0.001), while systemic O2 delivery increased with \u201cfresh\u201d RBCs (p &amp;lt; 0.0001) and \u201cfresh\u201d diluted RBCs (p &amp;lt; 0.05) but not with DCLHb. Systemic O2 extraction increased with DCLHb as compared to baseline (p &amp;lt; 0.05) and to the other groups (p &amp;lt; 0.0001). Improved tissue oxygenation was associated with an increase in blood pressure and a fall in arterial lactate in all groups. We conclude that transfusion of DCLHb or \u201cfresh\u201d RBCs was efficacious at increasing systemic O2 uptake in O2 supply\u2013dependent, septic rats.<\/jats:p>","DOI":"10.1164\/ajrccm.156.4.9609097","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:26:28Z","timestamp":1365081988000},"page":"1066-1072","source":"Crossref","is-referenced-by-count":58,"title":["Diaspirin Crosslinked Hemoglobin Improves Systemic Oxygen Uptake in Oxygen Supply\u2013dependent Septic Rats"],"prefix":"10.1093","volume":"156","author":[{"given":"ANDREAS W.","family":"SIELENK\u00c4MPER","sequence":"first","affiliation":[{"name":"A. C. Burton Vascular Biology Laboratory, Victoria Hospital Research Institute and University of Western Ontario, London, Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"IAN H.","family":"CHIN-YEE","sequence":"additional","affiliation":[{"name":"A. C. Burton Vascular Biology Laboratory, Victoria Hospital Research Institute and University of Western Ontario, London, Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CLAUDIO M.","family":"MARTIN","sequence":"additional","affiliation":[{"name":"A. C. Burton Vascular Biology Laboratory, Victoria Hospital Research Institute and University of Western Ontario, London, Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WILLIAM J.","family":"SIBBALD","sequence":"additional","affiliation":[{"name":"A. C. Burton Vascular Biology Laboratory, Victoria Hospital Research Institute and University of Western Ontario, London, Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1997,10,1]]},"reference":[{"key":"2026032709202265300_B1","doi-asserted-by":"crossref","first-page":"9929","DOI":"10.1016\/S0021-9258(18)67605-7","article-title":"Isolation and characterization of a new hemoglobin derivative cross-linked between the a chains (lysine 99a1, lysine 99a2).","volume":"21","author":"Chatterjee","year":"1986","journal-title":"J. Biol. Chem."},{"key":"2026032709202265300_B2","doi-asserted-by":"crossref","first-page":"17824","DOI":"10.1016\/S0021-9258(19)84647-1","article-title":"Equilibrium oxygen binding to human hemoglobin cross-linked between the a chains by bis(3,5-dibromosalicyl) fumarate.","volume":"264","author":"Vandergriff","year":"1989","journal-title":"J. Biol. Chem."},{"key":"2026032709202265300_B3"},{"key":"2026032709202265300_B4","first-page":"143","article-title":"Cross-linked hemoglobin solution as a resuscitative fluid after hemorrhage in the rat.","volume":"117","author":"Przybelski","year":"1991","journal-title":"J. Lab Clin. Med."},{"key":"2026032709202265300_B5","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1097\/00005373-199409000-00013","article-title":"The efficacy of diaspirin crosslinked hemoglobin solution resuscitation in a model of uncontrolled hemorrhage.","volume":"37","author":"Schultz","year":"1994","journal-title":"J. Trauma"},{"key":"2026032709202265300_B6","first-page":"299","article-title":"Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic hemodynamics and regional circulation in rats.","volume":"123","author":"Sharma","year":"1994","journal-title":"J. Lab. Clin. Med."},{"key":"2026032709202265300_B7","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/0024-3205(94)00566-4","article-title":"Effect of stroma-free hemoglobin and diaspirin cross-linked hemoglobin on the regional circulation and systemic hemodynamics.","volume":"55","author":"Gulati","year":"1994","journal-title":"Life Sci."},{"key":"2026032709202265300_B8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/00003246-199601000-00023","article-title":"Role of endothelin in the cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin.","volume":"24","author":"Gulati","year":"1996","journal-title":"Crit. Care Med."},{"key":"2026032709202265300_B9","first-page":"H1379","article-title":"Role of NO mechanism in cardiovascular effects of diaspirin cross-linked hemoglobin in anesthetized rats.","volume":"269","author":"Sharma","year":"1995","journal-title":"Am. J. Physiol."},{"key":"2026032709202265300_B10","first-page":"301","article-title":"A role for endothelin and nitric oxide in the pressor response to diaspirin cross-linked hemoglobin.","volume":"122","author":"Schultz","year":"1993","journal-title":"J. Lab. Clin. Med."},{"key":"2026032709202265300_B11"},{"key":"2026032709202265300_B12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1056\/NEJM197101142840205","article-title":"Viability and function of preserved red cells.","volume":"284","author":"Valeri","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"2026032709202265300_B13","first-page":"912","article-title":"Fluid loading increases oxygen consumption in septic patients with lactate acidosis.","volume":"131","author":"Haupt","year":"1985","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709202265300_B14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0883-9441(90)90052-B","article-title":"Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratory distress syndrome.","volume":"5","author":"Fenwick","year":"1990","journal-title":"J. Crit. Care"},{"key":"2026032709202265300_B15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0749-0704(18)30434-2","article-title":"Circulatory disturbances in multiple systems organ failure.","volume":"5","author":"Bersten","year":"1992","journal-title":"Crit. Care Clin."},{"key":"2026032709202265300_B16","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1152\/jappl.1988.64.6.2410","article-title":"Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia.","volume":"64","author":"Nelson","year":"1988","journal-title":"J. Appl. Physiol."},{"key":"2026032709202265300_B17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/00024382-199602000-00010","article-title":"The effects of diaspirin cross-linked hemoglobin in sepsis.","volume":"5","author":"Mourelatos","year":"1996","journal-title":"Shock"},{"key":"2026032709202265300_B18","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0749-0704(18)30435-4","article-title":"Oxygen delivery and uptake by peripheral tissues: physiology and pathophysiology.","volume":"5","author":"Schumacker","year":"1989","journal-title":"Crit. Care Clin."},{"key":"2026032709202265300_B19","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0272-5231(21)00195-7","article-title":"Peripheral oxygen uptake and delivery in health and disease.","volume":"4","author":"Cain","year":"1983","journal-title":"Clin. Chest Med."},{"key":"2026032709202265300_B20","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1097\/00003246-199705000-00004","article-title":"Transfusing RBCs stored in CPDA-1 for 28 days fails to improve tissue oxygenation in rats.","volume":"25","author":"Fitzgerald","year":"1997","journal-title":"Crit. Care Med."},{"key":"2026032709202265300_B21","first-page":"A464","article-title":"Dopexamine increases oxygen uptake compared to dobutamine in oxygen supply-dependent septic rats (abstract).","volume":"153","author":"Martin","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709202265300_B22","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1046\/j.1537-2995.1994.34894353469.x","article-title":"Points to consider on efficacy of hemoglobin- and perfluorocarbon-based oxygen carriers.","volume":"34","author":"Center for Biologics Evaluation and Research","year":"1994","journal-title":"Transfusion"},{"key":"2026032709202265300_B23","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1001\/jama.1993.03500230106037","article-title":"Effect of stored-blood transfusion on oxygen delivery in patients with sepsis.","volume":"269","author":"Marik","year":"1993","journal-title":"J.A.M.A."},{"key":"2026032709202265300_B24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1152\/jappl.1991.71.1.83","article-title":"Effects of anesthetic agents on systemic critical O2 delivery.","volume":"71","author":"Van der Linden","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"2026032709202265300_B25","first-page":"589a","article-title":"Storage of rat blood (abstract).","volume":"82","author":"Kovacs","year":"1993","journal-title":"Blood"},{"key":"2026032709202265300_B26","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1007\/BF03017957","article-title":"Bovine haemoglobin is more potent then autologous red blood cells in restoring muscular tissue oxygenation after profound isovolemic haemodilution in dogs.","volume":"43","author":"Standl","year":"1997","journal-title":"Can. J. Anesth."},{"key":"2026032709202265300_B27","first-page":"A27","article-title":"Pharmacokinetics of diaspirin cross-linked hemoglobin in a model of sepsis in the rat (abstract).","volume":"24","author":"d'Almeida","year":"1996","journal-title":"Crit. Care Med."},{"key":"2026032709202265300_B28","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/01.RES.75.2.357","article-title":"Heterogeneity of red blood cell perfusion in capillary networks supplied by a single arteriole in resting skeletal muscle.","volume":"75","author":"Ellis","year":"1994","journal-title":"Circ. Res."},{"key":"2026032709202265300_B29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/00024382-199602000-00006","article-title":"A selective inhibitor of inducible nitric oxide synthase prolongs survival in a rat model of bacterial peritonitis: comparison with two nonselective strategies.","volume":"5","author":"Aranow","year":"1996","journal-title":"Shock"},{"key":"2026032709202265300_B30","first-page":"323","article-title":"DCLHb flows through compressed lung capillaries that exclude red cells (abstract).","volume":"24","author":"Conheim","year":"1996","journal-title":"Art. Cells Blood Subs. Immob. Biotech."},{"key":"2026032709202265300_B31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0749-0704(18)30250-1","article-title":"The use of blood products in shock.","volume":"8","author":"Nacht","year":"1992","journal-title":"Crit. Care Clin."},{"key":"2026032709202265300_B32","first-page":"H889","article-title":"Influence of reduced red cell deformability on regional blood flow.","volume":"253","author":"Simchon","year":"1987","journal-title":"Am. J. Physiol."},{"key":"2026032709202265300_B33","first-page":"859","article-title":"Correlation between red blood cell deformability and changes in hemodynamic function.","volume":"116","author":"Langenfeld","year":"1994","journal-title":"Surgery"},{"key":"2026032709202265300_B34","first-page":"L28","article-title":"Endotoxin-induced adhesion of red blood cells to pulmonary artery endothelial cells.","volume":"270","author":"Tissot van Patot","year":"1996","journal-title":"Am. J. Physiol."},{"key":"2026032709202265300_B35","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1172\/JCI117562","article-title":"Microvascular perfusion is impaired in a rat model of normotensive sepsis.","volume":"94","author":"Lam","year":"1994","journal-title":"J. Clin. Invest."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/156\/4\/1066\/67448863\/ajrccm_156_4_1066.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/156\/4\/1066\/67448863\/ajrccm_156_4_1066.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:20:33Z","timestamp":1774617633000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/156\/4\/1066\/8530780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,10,1]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1997,10,1]]},"published-print":{"date-parts":[[1997,10,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.156.4.9609097","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1997,10]]},"published":{"date-parts":[[1997,10,1]]}}}