The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine

Moon-Massat, Paula F.; Scultetus, Anke; Arnaud, Françoise; Brown, Ammon; Haque, Ashraful; Saha, Banani; Kim, Bobby; Sagini, Eileen; McGwin, Gerald; Auker, Charles R.; McCarron, Richard M.; Freilich, Daniel

doi:10.1016/j.injury.2010.10.013

Cited by 30 publications

(26 citation statements)

References 25 publications

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“…17 One benefit of SNP over NaNO 2 in these short studies was the absence of petechiae and pulmonary congestion at the experimental endpoint. 17,18 This observation, and the fact that MetHb was lower with SNP, may reflect different mechanisms of action between these NO donors. SNP is a peripheral vasodilator that breaks down in the circulation to release NO.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18][19][20][21] HBOC-201 modifications and larginine co-infusion were ineffective and high-dose NaNO 2 caused unexpected adverse events. [15][16][17][18][19] NTG is efficacious in HS in swine and INO is efficacious in topload studies in mice and awake sheep. 9,22 SNP, used clinically to treat hypertensive crisis, has potent arterial vasodilatory properties.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…Studies using HBOC nitrite reductase activity to generate NO and N 2 O 3 to offset the NO scavenging in swine found an increase in the risk of pulmonary complications in a dosedependent fashion (101). In this study the swine underwent uncontrolled liver hemorrhage before receiving up to three 10 min 10 ml/kg infusions of HBOC with or without concurrent NaNO 2 .…”

Section: Strategies For the Design Of Hboc Formulationsmentioning

confidence: 93%

“…There was no significant effect between groups in indices of tissue oxygenation or survival. In this model, the transient nature of nitrite in offsetting HBOC-induced vasoconstriction makes it less clinically promising than anticipated and the combination of nitrite and HBOC appear to be more harmful than beneficial (101).…”

Section: Strategies For the Design Of Hboc Formulationsmentioning

confidence: 99%

HBOC Vasoactivity: Interplay Between Nitric Oxide Scavenging and Capacity to Generate Bioactive Nitric Oxide Species

Cabrales¹,

Friedman²

2013

Antioxidants & Redox Signaling

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Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature.

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“…Similarly, sodium nitrite has been used in a similar fluid resuscitation from hemorrhagic shock with HBOCs, and vasoconstriction was attenuated at high doses of nitrite (10). In addition to increased metHb levels, nitrite supplementations reduced platelet function and increased the risk of pulmonary complications (edema and congestion) (10,114). Pure NO inhalation has been used to treat NO depletion (174,175).…”

Section: No Supplementationmentioning

confidence: 99%

Examining and Mitigating Acellular Hemoglobin Vasoactivity

Cabrales

2013

Antioxidants & Redox Signaling

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Significance: There has been a striking advancement in our understanding of red cell substitutes over the past decade. Although regulatory oversight has influenced many aspects of product development in this period, those who have approached the demonstration of efficacy of red cell substitutes have failed to understand their implication at the level of the microcirculation, where blood interacts closely with tissue. Recent Advances: The understanding of the adverse effects of acellular hemoglobin (Hb)-based oxygen carriers (HBOCs) has fortunately expanded from Hb-induced renal toxicity to a more complete list of biochemical mechanism. In addition, various unexpected adverse reactions were seen in early clinical studies. The effects of the presence of acellular Hb in plasma are relatively unique because of the convergence of mechanical and biochemical natures. Critical Issues: Controlling the variables using genetic engineering and chemical modification to change specific characteristics of the Hb molecule may allow for solving the complex multivariate problems of acellular Hb vasoactivity. HBOCs may never be rendered free of negative effects; however, quantifying the nature and extent of microvascular complications establishes a platform for designing new ameliorative therapies. Future Directions: It is time to leave behind the study of vasoactivity and toxicity based on bench-top measurements of biochemical changes and those based solely on systemic parameters in vivo, and move to a more holistic analysis of the mechanisms creating the problems, complemented with meaningful studies of efficacy. Antioxid. Redox Signal. 18, 2329-2341.

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The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine

Cited by 30 publications

References 25 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

HBOC Vasoactivity: Interplay Between Nitric Oxide Scavenging and Capacity to Generate Bioactive Nitric Oxide Species

Examining and Mitigating Acellular Hemoglobin Vasoactivity

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