The Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers in Swine With Hemorrhagic Shock

Rice, Jennifer; Philbin, Nora; Light, Rick; Arnaud, Françoise; Steinbach, Thomas; McGwin, G.; Collier, Sarah; Malkevich, Nina; Moon-Massatt, Paula; Rentko, Virginia T.; Pearce, L. Bruce; Ahlers, Stephen; McCarron, Richard M.; Handrigan, Michael; Freilich, Daniel

doi:10.1097/ta.0b013e318058245e

Cited by 32 publications

(21 citation statements)

References 38 publications

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“…We confirmed that reduction of tetrameric/dimeric haemoglobin from 32% to <3% reduced HBOC-induced systemic and pulmonary hypertension and vascular resistance but further reduction to 0.4% had no additive effect. 25 Then, based on NO scavenging as the basis for HBOC vasoconstriction, we hypothesized that pharmacologic replenishment of blood NO could attenuate HBOCinduced hypertension and vascular resistance elevation. Clinically used vasodilators, NaNO 2 (for cyanide toxicity), SNP (for malignant hypertension), and NTG (for acute coronary syndromes) were investigated.…”

Section: Discussionmentioning

confidence: 99%

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: An exploratory study in a swine controlled haemorrhage model

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: An exploratory study in a swine controlled haemorrhage model

et al. 2012

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“…KCN (potassium cyanide), KFe(CN) 6 (potassium ferricyanide), and all other chemicals were purchased from Fisher Scientific (Pittsburgh, PA). HF cartridges were obtained from Spectrum Labs (Rancho Dominguez, CA).…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3][4] Although the exact mechanism of vasoconstriction upon HBOC transfusion is not known, there are two major hypotheses in the literature, namely, nitric oxide (NO) scavenging (by far the most popular one of the two) and oxygen oversupply. [5][6][7] To limit/prevent vasoconstriction by either mechanism, the size (i.e., molecular weight, MW) of the HBOC should be increased and free hemoglobin (Hb) and low-MW components should be removed from solution to reduce the interaction of the HBOC with the endothelium. 6,8,9 Therefore, strategies targeted toward increasing the size of HBOCs should be able to reduce these unwanted side effects.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7] To limit/prevent vasoconstriction by either mechanism, the size (i.e., molecular weight, MW) of the HBOC should be increased and free hemoglobin (Hb) and low-MW components should be removed from solution to reduce the interaction of the HBOC with the endothelium. 6,8,9 Therefore, strategies targeted toward increasing the size of HBOCs should be able to reduce these unwanted side effects. Polymerization of Hb represents such an approach.…”

Section: Introductionmentioning

confidence: 99%

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Biophysical Properties and Oxygenation Potential of High-Molecular-Weight Glutaraldehyde-Polymerized Human Hemoglobins Maintained in the Tense and Relaxed Quaternary States

Zhang

Jia²,

Guo³

et al. 2011

Tissue Engineering Part A

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Recent clinical evaluation of commercial glutaraldehyde-polymerized hemoglobins (PolyHbs) as transfusion solutions has demonstrated several adverse side effects. Chief among these is the hypertensive effect. Fortunately, previous studies have shown that the hypertensive effect can be attenuated by removing free hemoglobin (Hb) and low-molecular-weight (low-MW) PolyHbs from the PolyHb mixture. In this work, polymerized human Hb (PolyhHb) solutions were synthesized in two distinct quaternary states with high MW and subjected to extensive diafiltration to remove free Hb and low-MW PolyhHb components (<500 kDa). The resultant PolyhHb solutions possessed high MW, distinct quaternary state, distinct reactivities with O 2 and CO, similar NO deoxygenating rate constants, distinct autoxidation rate constants, high viscosity, and low colloid osmotic pressure. To preliminarily assess the ability of PolyhHb solutions to oxygenate surrounding tissues fed by a blood vessel, we evaluated the ability of PolyhHbs to transport O 2 to cultured hepatocytes in a mathematical model of a hollow fiber bioreactor. The structure of individual hollow fibers in the bioreactor is similar to that of a blood vessel and provides an easy way to assess the oxygenation potential of PolyhHbs without the need for expensive and time-consuming animal studies. It was observed that PolyhHbs with low O 2 affinities were more effective in oxygenating cultured hepatocytes inside the bioreactor than high O 2 affinity PolyhHbs. Taken together, our results show that it is possible to synthesize high-MW PolyhHbs with no free Hb and low-MW PolyhHb components that are capable of transporting O 2 to cultured cells/tissues.

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“…Their affinity for oxygen is lower than that of PRBC. Larger, heavier, highly polymerized HBOCs are less vasoactive than smaller molecules [47,48].…”

Section: Blood Substitutesmentioning

confidence: 99%

The treatment of traumatic shock: recent advances and unresolved questions

Sisák

Dewar

Butcher

et al. 2011

Eur J Trauma Emerg Surg

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Uncontrolled bleeding remains a leading cause of potentially preventable death after trauma. Timely, adequate resuscitation in traumatic shock is an essential, lifesaving aspect of polytrauma care. Whilst basic principles in the treatment of traumatic shock remain the same-achieving hemorrhage control and replacing lost volume, the way this is achieved has changed significantly in the last five years. The abandonment of blood pressure driven uncontrolled fluid resuscitation, the introduction of the concept of hemostatic resuscitation, and the increasing use of massive transfusion protocols have all contributed to an improvement in timely access to various blood products. The increase in knowledge regarding the pathophysiology of trauma, the availability of adjuncts, and the array of resuscitation monitoring options available have all contributed to a potentially improved approach to resuscitation. The purpose of this report is to review the most important advances in traumatic shock therapy in the last five years.

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The Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers in Swine With Hemorrhagic Shock

Cited by 32 publications

References 38 publications

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: An exploratory study in a swine controlled haemorrhage model

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: An exploratory study in a swine controlled haemorrhage model

Biophysical Properties and Oxygenation Potential of High-Molecular-Weight Glutaraldehyde-Polymerized Human Hemoglobins Maintained in the Tense and Relaxed Quaternary States

The treatment of traumatic shock: recent advances and unresolved questions

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