TY - JOUR
T1 - The effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers in swine with hemorrhagic shock
AU - Rice, Jennifer
AU - Philbin, Nora
AU - Light, Rick
AU - Arnaud, Françoise
AU - Steinbach, Thomas
AU - McGwin, Gerry
AU - Collier, Sarah
AU - Malkevich, Nina
AU - Moon-Massatt, Paula
AU - Rentko, Virginia
AU - Pearce, L. Bruce
AU - Ahlers, Stephen
AU - McCarron, Richard
AU - Handrigan, Michael
AU - Freilich, Daniel
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Hemoglobin-based oxygen carrier
KW - Hemorrhage
KW - Swine
KW - Tetrameric hemoglobin
KW - Vasoactivity
UR - http://www.scopus.com/inward/record.url?scp=43449135044&partnerID=8YFLogxK
U2 - 10.1097/TA.0b013e318058245e
DO - 10.1097/TA.0b013e318058245e
M3 - Article
C2 - 18469646
AN - SCOPUS:43449135044
SN - 0022-5282
VL - 64
SP - 1240
EP - 1257
JO - Journal of Trauma - Injury, Infection and Critical Care
JF - Journal of Trauma - Injury, Infection and Critical Care
IS - 5
ER -