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Microvascular and Systemic Impact of Resuscitation with Pegylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch In A Rat Model of transient hemorrhagic Shock.
Shock 2019S

Abstract

BACKGROUND

Hemorrhage is the leading cause of preventable, traumatic death. Currently, pre-hospital resuscitation fluids provide preload but not oxygen carrying capacity-a critical blood function that mitigates microvascular ischemia and tissue hypoxia during hemorrhagic shock. Solutions containing polymerized hemoglobin have been associated with vasoactive and hypertensive events. A novel hemoglobin-based oxygen carrier, modified with PEGylation and CO moieties (PEG-COHb) may overcome these limitations.

OBJECTIVES

To evaluate the systemic and microcirculatory effects of PEG-COHb as compared to the 6% hetastarch in a rat model of hemorrhagic shock.

METHODS

Male Sprague Dawley rats (N = 20) were subjected to severe, controlled, hemorrhagic shock. Animals were randomized to 20% estimated blood-volume resuscitation with either 6% hetastarch or PEG-COHb. Continuous, invasive, cardiovascular measurements and arterial blood gases were measured. Microcirculatory measurements of interstitial oxygenation (PISFO2) and vasoactivity helped model oxygen delivery in the spinotrapezius muscle using intravital and phosphorescence quenching microscopy.

RESULTS

Hemorrhage reduced mean arterial pressure (MAP), arteriolar diameter and PISFO2, and increased lactate 10-fold in both groups. Resuscitation with both PEG-COHb and hetastarch improved cardiovascular parameters. However, PEG-COHb treatment resulted in higher MAP (p < 0.001), improved PISFO2 (14 [PEG-COHb] vs 5 [hetastarch] mmHg; p < 0.0001), lower lactate post-resuscitation (p < 0.01) and extended survival from 90 min to 142 minutes (p < 0.001) as compared to the hetastarch group.

CONCLUSIONS

PEG-COHb improved MAP PISFO2, lactate and survival time as compared to 6% hetastarch resuscitation. Importantly, hypertension and vasoactivity were not detected in response to PEG-COHb resuscitation supporting further investigation of this resuscitation strategy.

Authors+Show Affiliations

Song Biotechnologies, Baltimore, MD.Department of Surgery, Maine Medical Center, Portland, ME.United States Army Institute of Surgical Research, Fort Sam Houston, TX.UT Health San Antonio, San Antonio, TX.United States Army Institute of Surgical Research, Fort Sam Houston, TX.Prolong Pharmaceuticals, South Plainfield, NJ.Prolong Pharmaceuticals, South Plainfield, NJ.Song Biotechnologies, Baltimore, MD.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31045989

Citation

Nugent, William H., et al. "Microvascular and Systemic Impact of Resuscitation With Pegylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch in a Rat Model of Transient Hemorrhagic Shock." Shock (Augusta, Ga.), 2019.
Nugent WH, Sheppard FR, Dubick MA, et al. Microvascular and Systemic Impact of Resuscitation with Pegylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch In A Rat Model of transient hemorrhagic Shock. Shock. 2019.
Nugent, W. H., Sheppard, F. R., Dubick, M. A., Cestero, R. F., Darlington, D. N., Jubin, R., ... Song, B. K. (2019). Microvascular and Systemic Impact of Resuscitation with Pegylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch In A Rat Model of transient hemorrhagic Shock. Shock (Augusta, Ga.), doi:10.1097/SHK.0000000000001370.
Nugent WH, et al. Microvascular and Systemic Impact of Resuscitation With Pegylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch in a Rat Model of Transient Hemorrhagic Shock. Shock. 2019 Apr 29; PubMed PMID: 31045989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microvascular and Systemic Impact of Resuscitation with Pegylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch In A Rat Model of transient hemorrhagic Shock. AU - Nugent,William H, AU - Sheppard,Forest R, AU - Dubick,Michael A, AU - Cestero,Ramon F, AU - Darlington,Daniel N, AU - Jubin,Ronald, AU - Abuchowski,Abe, AU - Song,Bjorn K, Y1 - 2019/04/29/ PY - 2019/5/3/entrez JF - Shock (Augusta, Ga.) JO - Shock N2 - BACKGROUND: Hemorrhage is the leading cause of preventable, traumatic death. Currently, pre-hospital resuscitation fluids provide preload but not oxygen carrying capacity-a critical blood function that mitigates microvascular ischemia and tissue hypoxia during hemorrhagic shock. Solutions containing polymerized hemoglobin have been associated with vasoactive and hypertensive events. A novel hemoglobin-based oxygen carrier, modified with PEGylation and CO moieties (PEG-COHb) may overcome these limitations. OBJECTIVES: To evaluate the systemic and microcirculatory effects of PEG-COHb as compared to the 6% hetastarch in a rat model of hemorrhagic shock. METHODS: Male Sprague Dawley rats (N = 20) were subjected to severe, controlled, hemorrhagic shock. Animals were randomized to 20% estimated blood-volume resuscitation with either 6% hetastarch or PEG-COHb. Continuous, invasive, cardiovascular measurements and arterial blood gases were measured. Microcirculatory measurements of interstitial oxygenation (PISFO2) and vasoactivity helped model oxygen delivery in the spinotrapezius muscle using intravital and phosphorescence quenching microscopy. RESULTS: Hemorrhage reduced mean arterial pressure (MAP), arteriolar diameter and PISFO2, and increased lactate 10-fold in both groups. Resuscitation with both PEG-COHb and hetastarch improved cardiovascular parameters. However, PEG-COHb treatment resulted in higher MAP (p < 0.001), improved PISFO2 (14 [PEG-COHb] vs 5 [hetastarch] mmHg; p < 0.0001), lower lactate post-resuscitation (p < 0.01) and extended survival from 90 min to 142 minutes (p < 0.001) as compared to the hetastarch group. CONCLUSIONS: PEG-COHb improved MAP PISFO2, lactate and survival time as compared to 6% hetastarch resuscitation. Importantly, hypertension and vasoactivity were not detected in response to PEG-COHb resuscitation supporting further investigation of this resuscitation strategy. SN - 1540-0514 UR - https://www.unboundmedicine.com/medline/citation/31045989/Microvascular_and_Systemic_Impact_of_Resuscitation_with_Pegylated_Carboxyhemoglobin-Based_Oxygen_Carrier_or_Hetastarch_In_A_Rat_Model_of_transient_hemorrhagic_Shock L2 - http://dx.doi.org/10.1097/SHK.0000000000001370 DB - PRIME DP - Unbound Medicine ER -