title: Experimental assessment of oxygen homeostasis during acute hemodilution: the integrated role of hemoglobin concentration and blood pressure.
abstract: BACKGROUND
  Low hemoglobin concentration (Hb) and low mean arterial blood pressure (MAP) impact outcomes in critically ill patients. We utilized an experimental model of "normotensive" vs. "hypotensive" acute hemodilutional anemia to test whether optimal tissue perfusion is dependent on both Hb and MAP during acute blood loss and fluid resuscitation, and to assess the value of direct measurements of the partial pressure of oxygen in tissue (PtO2).
  
  
  METHODS
  Twenty-nine anesthetized rats underwent 40% isovolemic hemodilution (1:1) (or sham-hemodilution control, n = 4) with either hydroxyethyl starch (HES) (n = 14, normotensive anemia) or saline (n = 11, hypotensive anemia) to reach a target Hb value near 70 g/L. The partial pressure of oxygen in the brain and skeletal muscle tissue (PtO2) were measured by phosphorescence quenching of oxygen using G4 Oxyphor. Mean arterial pressure (MAP), heart rate, temperature, arterial and venous co-oximetry, blood gases, and lactate were assessed at baseline and for 60 min after hemodilution. Cardiac output (CO) was measured at baseline and immediately after hemodilution. Data were analyzed by repeated measures two-way ANOVA.
  
  
  RESULTS
  Following "normotensive" hemodilution with HES, Hb was reduced to 66 ± 6 g/L, CO increased (p < 0.05), and MAP was maintained. These conditions resulted in a reduction in brain PtO2(22.1 ± 5.6 mmHg to 17.5 ± 4.4 mmHg, p < 0.05), unchanged muscle PO2, and an increase in venous oxygen extraction. Following "hypotensive" hemodilution with saline, Hb was reduced to 79 ± 5 g/L and both CO and MAP were decreased (P < 0.05). These conditions resulted in a more severe reduction in brain PtO2(23.2 ± 8.2 to 10.7 ± 3.6 mmHg (p < 0.05), a reduction in muscle PtO2(44.5 ± 11.0 to 19.9 ± 12.4 mmHg, p < 0.05), a further increase in venous oxygen extraction, and a threefold increase in systemic lactate levels (p < 0.05).
  
  
  CONCLUSIONS
  Acute normotensive anemia (HES hemodilution) was associated with a subtle decrease in brain tissue PtO2without clear evidence of global tissue hypoperfusion. By contrast, acute hypotensive anemia (saline hemodilution) resulted in a profound decrease in both brain and muscle tissue PtO2and evidence of inadequate global perfusion (lactic acidosis). These data emphasize the importance of maintaining CO and MAP to ensure adequacy of vital organ oxygen delivery during acute anemia. Improved methods of assessing PtO2may provide an earlier warning signal of vital organ hypoperfusion.
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Kei
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.|Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Mistry
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Albert K Y
authors.initials: AKY
authors.lastname: Tsui
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.|Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Liu
authors.affiliation: Division of Pediatric Critical Care Medicine, Washington University in Saint Louis, Saint Louis, MO, 63130, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Division of Pediatric Critical Care Medicine, Washington University in Saint Louis, Saint Louis, MO, 63130, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Doctor
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Wilson
authors.affiliation: Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.|Department of Medicine, Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Desjardins
authors.affiliation: Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.|Department of Medicine, Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Connelly
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.|Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.|Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. hareg@smh.ca.|Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. hareg@smh.ca.|Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. hareg@smh.ca.
authors.forename: Gregory M T
authors.initials: GMT
authors.lastname: Hare
keywords: Anemia; Cardiac output; Hemodilution; Hypotension; Mean arterial pressure; Partial pressure of oxygen in tissue