title: Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase in critical O(2) delivery.
abstract: We hypothesized that support of arterial perfusion pressure with diaspirin cross-linked Hb (DCLHb) would prevent the sepsis-induced attenuation in the systemic O(2) delivery-O(2) uptake relationship. Awake septic rats were treated with a chronic infusion of DCLHb or a reference treatment [norepinephrine (NE)] to increase mean arterial pressure by 10-20% over 18 h. Septic and sham control groups received normal saline. Isovolemic hemodilution to create anemic hypoxia was then performed in a metabolic box during continuous measurement of systemic O(2) uptake. O(2) delivery was calculated from hemodynamic variables, and the critical point of O(2) delivery (DO(2 crit)) was determined using piecewise regression analysis of the O(2) delivery-O(2) uptake relationship. Sepsis increased DO(2 crit) from 4.99 +/- 0.17 to 6.69 +/- 0.42 ml x min(-1) x 100 g(-1) (P < 0.01), while O(2) extraction capacity was decreased (P < 0.05). DCLHb and NE infusion prevented the sepsis-induced increase in DO(2 crit) [4.56 +/- 0.42 ml x min(-1) x 100 g(-1) (P < 0.01) and 5.04 +/- 0.56 ml x min(-1) x 100 g(-1) (P < 0.05), respectively]. This was explained by a 59% increase in O(2) extraction capacity in the DCLHb group compared with septic controls (P < 0.05), whereas NE treatment decreased systemic O(2) uptake in anemic hypoxia (1.51 +/- 0.08 vs. 1.87 +/- 0.1 ml x min(-1) x 100 g(-1) in septic controls, P < 0.05). We conclude that DCLHb ameliorated O(2) extraction capacity in the septic microcirculation, whereas NE decreased the metabolic demands of the tissues.
authors.affiliation: The A. C. Burton Vascular Biology Laboratory, Victoria Hospital Research Institute, and The University of Western Ontario, London, Ontario, Canada N6A 4G5.
authors.forename: A W
authors.initials: AW
authors.lastname: Sielenkämper
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.forename: O
authors.initials: O
authors.lastname: Eichelbrönner
authors.forename: T
authors.initials: T
authors.lastname: MacDonald
authors.forename: C M
authors.initials: CM
authors.lastname: Martin
authors.forename: I H
authors.initials: IH
authors.lastname: Chin-Yee
authors.forename: W J
authors.initials: WJ
authors.lastname: Sibbald
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001424:Bacterial Infections / Q000097:blood* / Q000378:metabolism; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D006438:Hemodilution; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D014662:Vasoconstrictor Agents; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin; D010100:Oxygen; D009638:Norepinephrine