The effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers in swine with hemorrhagic shock.
BACKGROUND
Some hemoglobin-based oxygen carriers (HBOCs) improve outcome in animal models of hemorrhagic shock (HS) in comparison with standard asanguinous resuscitation fluids. Nevertheless, concern about intrinsic vasoactivity, linked in part to low-molecular weight (MW) hemoglobin (Hb), has slowed HBOC development. We assessed the impact of decreasing the low-MW Hb component of bovine HBOC on vasoactivity in severe HS.


METHODS
Anesthetized invasively monitored swine were hemorrhaged 55% blood volume and resuscitated with bovine HBOC containing 31% (31 TD [HBOC-301]), 2% (2 TD [HBOC-201]), or 0.4% (0.4 TD) low-MW Hb. Pigs received four 10 mL/kg infusions over 60 minutes, hospital arrival was simulated at 75 minutes, organ blood flow (BF) was evaluated by microsphere injection, and monitoring was continued for 4 hours followed by complete necrotic evaluation.


RESULTS
There were few differences between 2 TD and 0.4 TD. Thirty-one TD pigs had higher systemic and pulmonary blood pressure (BP), systemic vascular resistance index, and pulmonary artery wedge pressure, compared with 2 TD or 0.4 TD (p < 0.01); however, pigs in all groups had at least mildly elevated BP. Transcutaneous tissue oxygenation, base excess, and mixed venous oxygen saturation were similar across groups; lactate and methemoglobin were highest with 0.4 TD (p < 0.03). There were no group differences in BF. Over time, myocardial BF increased and hepatic BF decreased in all groups (for 31 TD, p < 0.05); renal BF was unchanged in all groups. There were no group differences in heart, lung, or liver histopathology, and survival.


CONCLUSIONS
Although purification from 31% to 2% low-MW Hb content significantly decreased vasoactive responses, further purification to 0.4% had no additional clinically measurable effects in severe HS. If further diminution in HBOC vasoactivity is desired for use in HS, additional technical approaches may be required.
Rice
Jennifer
J
Naval Medical Research Center, Silver Spring, Maryland, USA.
Philbin
Nora
N
Light
Rick
R
Arnaud
Françoise
F
Steinbach
Thomas
T
McGwin
Gerry
G
Collier
Sarah
S
Malkevich
Nina
N
Moon-Massatt
Paula
P
Rentko
Virginia
V
Pearce
L Bruce
LB
Ahlers
Stephen
S
McCarron
Richard
R
Handrigan
Michael
M
Freilich
Daniel
D
D000818:Animals; D001794:Blood Pressure; D001802:Blood Substitutes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D008970:Molecular Weight; D012039:Regional Blood Flow; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013552:Swine
D001802:Blood Substitutes