Bovine polymerized hemoglobin (hemoglobin-based oxygen carrier-201) resuscitation in three swine models of hemorrhagic shock with militarily relevant delayed evacuation—Effects on histopathology and organ function*

Johnson, Todd O.; Arnaud, Françoise; Dong, Feng; Philbin, Nora; Rice, Jennifer; Asher, Ludmila V.; Arrisueno, Martin; Warndorf, Matthew; Gurney, Jennifer M; McGwin, Gerald; Kaplan, Lewis J.; Flournoy, W. Shannon; Apple, Fred S.; Pearce, L. Bruce; Ahlers, Stephen; McCarron, Richard M.; Freilich, Daniel

doi:10.1097/01.ccm.0000215824.85190.89

Cited by 36 publications

(18 citation statements)

References 55 publications

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“…HBOC-201 improves tissue oxygenation, reverses anaerobic metabolism, and increases survival in HS animal models [8][9][10][11][12][13][14][15], but HBOCs' effects on host immune responses are not well described. In vitro, at high concentrations, HBOC-201 has immune activating potential, especially enhancement of neutrophilic b 2 integrin (CD11b) expression [16].…”

Section: Discussionmentioning

confidence: 94%

“…These data are important because improved outcome in animal models of HS [8][9][10][11][12][13][14][15] has prompted the U.S. Navy to propose a prehospital clinical trial in HS, comparing HBOC-201 and Lactated Ringer's (LR) solution. Thus, comprehensive understanding of potential secondary effects on vital physiologic functions is essential to optimize trial design and prediction of benefit: risk ratio in humans.…”

Section: Immune Responses In Swine After Hemorrhagic Shockmentioning

confidence: 98%

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Innate Immune Responses in Swine Resuscitated from Severe Traumatic Hemorrhagic Shock with Hemoglobin-Based Oxygen Carrier-201

Hall

Malkevich

Handrigan

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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Hemoglobin-based oxygen carrier-201 transports oxygen and improves survival in swine with hemorrhagic shock, but has potential to be immune activating. Herein, we evaluated HBOC-201's immune effects in swine with more severe hemorrhagic shock due to soft tissue injury and 55% blood volume catheter withdrawal over 15 minutes followed by fluid resuscitation at 20 minutes with HBOC-201, Hextend, or no treatment (NON) before hospital arrival. Survival rates were similar with HBOC-201 and Hextend (p > 0.05), but were higher than in (p = 0.007). There were no significant group differences in blood cell count, percentages of leukocyte sub-populations and immunophenotype (CD4:CD8 ratio), adhesion markers expression (neutrophil CD11b; monocyte or neutrophil CD49d) and apoptosis. There was a trend to higher plasma IL-10 in HBOC-201 and groups vs. Hextend. We conclude that in swine with severe controlled HS and soft tissue injury, immune responses are similar with resuscitation with HBOC-201 and Hextend.

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Section: Discussionmentioning

confidence: 94%

Section: Immune Responses In Swine After Hemorrhagic Shockmentioning

confidence: 98%

Innate Immune Responses in Swine Resuscitated from Severe Traumatic Hemorrhagic Shock with Hemoglobin-Based Oxygen Carrier-201

Hall

Malkevich

Handrigan

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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“…39 In swine HS models, HBOC-201 resuscitation resulted in less or similar myocardial necrosis, fibroplasia/ histiocytic infiltration, and troponin elevation versus standard fluid. 9,40 Thus, preclinical HS studies suggest that in comparison with asanguineous fluids, HBOC-201 resuscitation is unlikely be harmful to myocardium in HS. HBOC-201 was also myocardial protective in models of acute coronary occlusion.…”

Section: Hboc-201 Vasoactivity In a Phase III Clinical Trialmentioning

confidence: 97%

HBOC-201 Vasoactivity in a Phase III Clinical Trial in Orthopedic Surgery Subjects—Extrapolation of Potential Risk for Acute Trauma Trials

Freilich

Pearce

Pitman

et al. 2009

Journal of Trauma: Injury, Infection &Amp; Critical Care

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Our limited HEM-0115 safety analysis shows that key potentially vasoactivity-related adverse safety signals were more frequent with HBOC-201 than RBC in older patients undergoing orthopedic surgery with rapid access to safe blood transfusions. That incidences of these safety signals were generally lower and group differences narrowed in subpopulations with stable trauma, hypotension, and younger age, suggests an acceptable safety profile in younger acute trauma populations, especially in settings where rapid access to safe blood transfusions is unavailable; confirmation in controlled clinical trials is urgently warranted.

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“…Pigs were euthanized for necropsy and histological analysis at the end of the experiment. Methods and results of the histopathologic data have been previously published (9).…”

Section: Simulated Hospital Phase: Recovery and Long Term Survivalmentioning

confidence: 99%

Bovine Polymerized Hemoglobin Versus Hextend Resuscitation in a Swine Model of Severe Controlled Hemorrhagic Shock With Delay to Definitive Care

Rice

Philbin²,

McGwin

et al. 2006

Shock

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To compare the efficacy of low-volume resuscitation with bovine polymerized hemoglobin (HBOC-201) versus hetastarch (HEX) in an intermediate severity combat-relevant hemorrhagic shock swine model with a simulated delay to hospital care. Twenty-four anesthetized pigs were hemorrhaged 55% estimated blood volume in conjunction with a 5-min rectus abdominus crush. At 20 min, pigs were resuscitated with 10 mL/kg of HBOC-201 or HEX or nothing (NON); resuscitated pigs received additional infusions (5 mL/kg) at 30, 60, 120, or 180 min if hypotension or tachycardia persisted. Pigs were monitored for a 4-h "prehospital" period. At 4-h, hospital arrival was simulated: surgical sites were repaired, blood, or saline provided, and pigs were recovered from anesthesia. Pigs were monitored for 72 h and then killed for histological evaluation. One hundred percent (8/8) of HBOC-201-, 75% (6/8) of HEX-, and 25% (2/8) of NON-resuscitated pigs survived to 72 h (P = 0.007 overall, HBOC vs. HEX P > 0.05). Mean arterial pressure and mean pulmonary arterial pressure were highest in the HBOC-201 group (P < 0.001), and HR was lowest (P < 0.001). HBOC-201- and HEX-resuscitated pigs had comparable cardiac index and prehospital fluid requirements. HBOC-201 pigs had higher transcutaneous tissue oxygen tension, P < 0.001) and lower urine output (P < 0.001). At simulated hospital arrival, no HBOC-201 pigs required additional fluids or blood transfusion. In contrast, 100% of HEX pigs required blood transfusions (P < 0.01). In this swine model of controlled hemorrhage with low-volume resuscitation and delayed definitive care, HBOC-201 pigs had improved hemodynamics, transcutaneous tissue oxygen tension, and transfusion avoidance compared with HEX.

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Bovine polymerized hemoglobin (hemoglobin-based oxygen carrier-201) resuscitation in three swine models of hemorrhagic shock with militarily relevant delayed evacuation—Effects on histopathology and organ function*

Cited by 36 publications

References 55 publications

Innate Immune Responses in Swine Resuscitated from Severe Traumatic Hemorrhagic Shock with Hemoglobin-Based Oxygen Carrier-201

Innate Immune Responses in Swine Resuscitated from Severe Traumatic Hemorrhagic Shock with Hemoglobin-Based Oxygen Carrier-201

HBOC-201 Vasoactivity in a Phase III Clinical Trial in Orthopedic Surgery Subjects—Extrapolation of Potential Risk for Acute Trauma Trials

Bovine Polymerized Hemoglobin Versus Hextend Resuscitation in a Swine Model of Severe Controlled Hemorrhagic Shock With Delay to Definitive Care

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