title: The effect of RSR13, a synthetic allosteric modifier of hemoglobin, on brain tissue pO2 (measured by EPR oximetry) following severe hemorrhagic shock in rats.
abstract: RSR13 is a synthetic allosteric modifier of hemoglobin that decreases the oxygen binding affinity of hemoglobin, potentially increasing oxygen availability to hypoxic tissues. Using in vivo EPR to directly measure cortical pO2, we examined whether RSR13 would improve brain tissue pO2 following severe hemorrhagic shock in rats. Hemorrhagic shock was induced by withdrawing blood (2.7-2.8 mL/100 g/15 min). Following a 30 min shock period, resuscitation was performed by infusion with Ringer lactate plus RSR13 (150 mg/kg) or saline (control). Following hemorrhage, brain pO2 decreased by about 14 mm Hg in both groups. Following crystalloid resuscitation brain pO2 remained depressed in the control group but returned to the pre-hemorrhage values in the rats that received RSR13. RSR13 immediately increased and maintained the paO2 while controls had a very gradual increase towards pre-hemorrhage values. There was no difference in the blood pressure or heart rate between groups. RSR13 may have useful applications to decrease the effects of acute hemorrhagic hypoxemia by increasing brain oxygenation.
authors.affiliation: EPR Center for the Study of Viable Systems, Department of Radiology, 7785 Vail Dartmouth Medical School, Hanover, NH, USA.
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyake
authors.forename: Oleg Y
authors.initials: OY
authors.lastname: Grinberg
authors.forename: Huagang
authors.initials: H
authors.lastname: Hou
authors.forename: Robert P
authors.initials: RP
authors.lastname: Steffen
authors.forename: Hisham
authors.initials: H
authors.lastname: Elkadi
authors.forename: Harold M
authors.initials: HM
authors.lastname: Swartz
mesh_terms: D000494:Allosteric Regulation; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D010092:Oximetry / Q000379:methods; D010100:Oxygen / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D006454:Hemoglobins; D011422:Propionates; C067396:efaproxiral; D010100:Oxygen