Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock

C. VanderMolen; N. Malkevich; N. Philbin; J. Rice; S. Collier; C. Hall; S. Ahlers; R. McCarron; D. Freilich; G. McGwin; L. Bruce Pearce

doi:10.1080/10731190701586228

Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock

C. VanderMolen, N. Malkevich^*, N. Philbin, J. Rice, S. Collier, C. Hall, S. Ahlers, R. McCarron, D. Freilich, G. McGwin, L. Bruce Pearce

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Hemoglobin-based oxygen carriers (HBOCs) show potential as safe, efficacious, pre-hospital resuscitation fluids. The major criticism of HBOC-201 is its vasoactive property, attributed partially to low-molecular weight (low-MW) tetrameric/dimeric (TD) hemoglobin (Hb) in HBOC solution. Here we sought to determine whether resuscitation with decreasing concentrations of low-MW Hb component of HBOC affects immune responses in hemorrhagic swine. 28 anesthetized swine underwent a soft muscle crush and controlled hemorrhage of 55% blood volume, followed by resuscitation with HBOC containing 31%, 2%, or 0.4% low-MW Hb in four 10 ml/kg infusions at 20, 30, 45 and 60 minutes before hospital arrival at 75 minutes. IL-10, cell activation and adhesion markers and CD4:CD8 ratio remained unchanged in all 3 groups compared to baseline. Leukocyte apoptosis was equally elevated across all groups. Purification from 31% to 0.4% low-MW Hb in HBOC solution did not alter immune effects in a swine model of severe controlled hemorrhagic shock.

Original language	English
Pages (from-to)	507-517
Number of pages	11
Journal	Artificial Cells, Blood Substitutes, and Biotechnology
Volume	35
Issue number	5
DOIs	https://doi.org/10.1080/10731190701586228
State	Published - Sep 2007
Externally published	Yes

Keywords

HBOCs
Hemorrhagic shock
Innate immunity
Resuscitation
Swine

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10.1080/10731190701586228

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VanderMolen, C., Malkevich, N., Philbin, N., Rice, J., Collier, S., Hall, C., Ahlers, S., McCarron, R., Freilich, D., McGwin, G., & Pearce, L. B. (2007). Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock. Artificial Cells, Blood Substitutes, and Biotechnology, 35(5), 507-517. https://doi.org/10.1080/10731190701586228

@article{f508a52a7e75421685a635927fdeb521,

title = "Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock",

abstract = "Hemoglobin-based oxygen carriers (HBOCs) show potential as safe, efficacious, pre-hospital resuscitation fluids. The major criticism of HBOC-201 is its vasoactive property, attributed partially to low-molecular weight (low-MW) tetrameric/dimeric (TD) hemoglobin (Hb) in HBOC solution. Here we sought to determine whether resuscitation with decreasing concentrations of low-MW Hb component of HBOC affects immune responses in hemorrhagic swine. 28 anesthetized swine underwent a soft muscle crush and controlled hemorrhage of 55% blood volume, followed by resuscitation with HBOC containing 31%, 2%, or 0.4% low-MW Hb in four 10 ml/kg infusions at 20, 30, 45 and 60 minutes before hospital arrival at 75 minutes. IL-10, cell activation and adhesion markers and CD4:CD8 ratio remained unchanged in all 3 groups compared to baseline. Leukocyte apoptosis was equally elevated across all groups. Purification from 31% to 0.4% low-MW Hb in HBOC solution did not alter immune effects in a swine model of severe controlled hemorrhagic shock.",

keywords = "HBOCs, Hemorrhagic shock, Innate immunity, Resuscitation, Swine",

author = "C. VanderMolen and N. Malkevich and N. Philbin and J. Rice and S. Collier and C. Hall and S. Ahlers and R. McCarron and D. Freilich and G. McGwin and Pearce, {L. Bruce}",

note = "Funding Information: The authors thank HM1 Benjamin Esperat and Ms. Noemy Carballo for their excellent technical support. The studies described herein were entirely funded by the U.S. Government, Office of Naval Research, Work Unit Number 602236N.4426.W26.A0241. Dr. L. Bruce Pearce is an employee of Biopure Corp. and has financial interest in the subject material, HBOC-201. Dr. Pearce{\textquoteright}s contribution to the manuscript was limited to editing of the study design, protocol and manuscript. NMRC and Biopure Corp. have a Cooperative Research and Development Agreement for the evaluation of HBOC-201 in trauma clinical trials and a Materials Transfer Agreement for the supply of HBOC for pre-clinical studies. There are no funds transferred from Biopure to NMRC in either of these agreements.",

year = "2007",

month = sep,

doi = "10.1080/10731190701586228",

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VanderMolen, C, Malkevich, N, Philbin, N, Rice, J, Collier, S, Hall, C, Ahlers, S, McCarron, R, Freilich, D, McGwin, G & Pearce, LB 2007, 'Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock', Artificial Cells, Blood Substitutes, and Biotechnology, vol. 35, no. 5, pp. 507-517. https://doi.org/10.1080/10731190701586228

Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock. / VanderMolen, C.; Malkevich, N.; Philbin, N. et al.
In: Artificial Cells, Blood Substitutes, and Biotechnology, Vol. 35, No. 5, 09.2007, p. 507-517.

Research output: Contribution to journal › Article › peer-review

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AU - VanderMolen, C.

AU - Malkevich, N.

AU - Philbin, N.

AU - Rice, J.

AU - Collier, S.

AU - Hall, C.

AU - Ahlers, S.

AU - McCarron, R.

AU - Freilich, D.

AU - McGwin, G.

AU - Pearce, L. Bruce

N1 - Funding Information: The authors thank HM1 Benjamin Esperat and Ms. Noemy Carballo for their excellent technical support. The studies described herein were entirely funded by the U.S. Government, Office of Naval Research, Work Unit Number 602236N.4426.W26.A0241. Dr. L. Bruce Pearce is an employee of Biopure Corp. and has financial interest in the subject material, HBOC-201. Dr. Pearce’s contribution to the manuscript was limited to editing of the study design, protocol and manuscript. NMRC and Biopure Corp. have a Cooperative Research and Development Agreement for the evaluation of HBOC-201 in trauma clinical trials and a Materials Transfer Agreement for the supply of HBOC for pre-clinical studies. There are no funds transferred from Biopure to NMRC in either of these agreements.

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N2 - Hemoglobin-based oxygen carriers (HBOCs) show potential as safe, efficacious, pre-hospital resuscitation fluids. The major criticism of HBOC-201 is its vasoactive property, attributed partially to low-molecular weight (low-MW) tetrameric/dimeric (TD) hemoglobin (Hb) in HBOC solution. Here we sought to determine whether resuscitation with decreasing concentrations of low-MW Hb component of HBOC affects immune responses in hemorrhagic swine. 28 anesthetized swine underwent a soft muscle crush and controlled hemorrhage of 55% blood volume, followed by resuscitation with HBOC containing 31%, 2%, or 0.4% low-MW Hb in four 10 ml/kg infusions at 20, 30, 45 and 60 minutes before hospital arrival at 75 minutes. IL-10, cell activation and adhesion markers and CD4:CD8 ratio remained unchanged in all 3 groups compared to baseline. Leukocyte apoptosis was equally elevated across all groups. Purification from 31% to 0.4% low-MW Hb in HBOC solution did not alter immune effects in a swine model of severe controlled hemorrhagic shock.

AB - Hemoglobin-based oxygen carriers (HBOCs) show potential as safe, efficacious, pre-hospital resuscitation fluids. The major criticism of HBOC-201 is its vasoactive property, attributed partially to low-molecular weight (low-MW) tetrameric/dimeric (TD) hemoglobin (Hb) in HBOC solution. Here we sought to determine whether resuscitation with decreasing concentrations of low-MW Hb component of HBOC affects immune responses in hemorrhagic swine. 28 anesthetized swine underwent a soft muscle crush and controlled hemorrhage of 55% blood volume, followed by resuscitation with HBOC containing 31%, 2%, or 0.4% low-MW Hb in four 10 ml/kg infusions at 20, 30, 45 and 60 minutes before hospital arrival at 75 minutes. IL-10, cell activation and adhesion markers and CD4:CD8 ratio remained unchanged in all 3 groups compared to baseline. Leukocyte apoptosis was equally elevated across all groups. Purification from 31% to 0.4% low-MW Hb in HBOC solution did not alter immune effects in a swine model of severe controlled hemorrhagic shock.

KW - HBOCs

KW - Hemorrhagic shock

KW - Innate immunity

KW - Resuscitation

KW - Swine

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IS - 5

ER -

Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock

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Keywords

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