Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact.
Sanguinate, a polyethylene glycol-conjugated carboxyhemoglobin, was investigated for cerebral vasoactivity in healthy male Sprague-Dawley rats (Study 1) and for its ability to increase brain tissue oxygen pressure (PbtO2) after controlled cortical impact (CCI) - traumatic brain injury (TBI) (Study 2). In both studies ketamine-acepromazine anesthetized rats were ventilated with 40% O2. In Study 1, a cranial window was used to measure the diameters of medium - (50-100μm) and small-sized (<50μm) pial arterioles before and after four serial infusions of Sanguinate (8mL/kg/h, cumulative 16mL/kg IV), volume-matched Hextend, or normal saline. In Study 2, PbtO2 was measured using a phosphorescence quenching method before TBI, 15min after TBI (T15) and then every 10min thereafter for 155min. At T15, rats received either 8mL/kg IV Sanguinate (40mL/kg/h) or no treatment (saline, 4mL/kg/h). Results showed: 1) in healthy rats, percentage changes in pial arteriole diameter were the same among the groups, 2) in TBI rats, PbtO2 decreased from 36.5±3.9mmHg to 19.8±3.0mmHg at T15 in both groups after TBI and did not recover in either group for the rest of the study, and 3) MAP increased 16±4mmHg and 36±5mmHg after Sanguinate in healthy and TBI rats, respectively, while MAP was unchanged in control groups. In conclusion, Sanguinate did not cause vasoconstriction in the cerebral pial arterioles of healthy rats but it also did not acutely increase PbtO2 when administered after TBI. Sanguinate was associated with an increase in MAP in both studies.
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: saad.h.mullah.ctr@mail.mil.
Saad H
SH
Mullah
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: rania.abutarboush.ctr@mail.mil.
Rania
R
Abutarboush
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: paula.f.moon-massat.ctr@mail.mil.
Paula F
PF
Moon-Massat
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: biswajit.k.saha.ctr@mail.mil.
Biswajit K
BK
Saha
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: ashraful.haque.ctr@mail.mil.
Ashraful
A
Haque
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: peter.b.walker.mil@mail.mil.
Peter B
PB
Walker
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA. Electronic address: charles.r.auker.ctr@mail.mil.
Charles R
CR
Auker
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA; Uniformed Services University of the Health Sciences, Department of Surgery, Bethesda, MD 20814, USA. Electronic address: francoise.arnaud.ctr@mail.mil.
Francoise G
FG
Arnaud
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA; Uniformed Services University of the Health Sciences, Department of Surgery, Bethesda, MD 20814, USA. Electronic address: richard.m.mccarron.civ@mail.mil.
Richard M
RM
McCarron
Naval Medical Research Center, NeuroTrauma Department, 503 Robert Grant Avenue Silver Spring, MD 20910, USA; Uniformed Services University of the Health Sciences, Department of Surgery, Bethesda, MD 20814, USA. Electronic address: anke.h.scultetus2.ctr@mail.mil.
Anke H
AH
Scultetus
D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002263:Carboxyhemoglobin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010841:Pia Mater / Q000098:blood supply*; D010952:Plasma Substitutes / Q000494:pharmacology* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D011092:Polyethylene Glycols; D002263:Carboxyhemoglobin; D010100:Oxygen
Cerebral oxygenation; Hemoglobin-based oxygen carrier; Intravital microscopy; Microcirculation; Oxygen therapeutic; Phosphorescence quenching method; Polyethylene glycol-conjugated carboxyhemoglobin; Traumatic brain injury