Inhaled nitric oxide prevents systemic and pulmonary vasoconstriction due to hemoglobin-based oxygen carrier infusion: A case report

Marrazzo, Francesco; Larson, Grant; Lama, Tenzing T.; Droghi, Maddalena Teggia; Joyce, Maurice F.; Ichinose, Fumito; Watkins, Michael T.; Stowell, Christopher P.; Crowley, Jerome

doi:10.1016/j.jcrc.2018.04.008

Cited by 11 publications

(9 citation statements)

References 13 publications

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“…Furthermore, other researchers have noted similar airway irritation and irregular breathing in guinea pigs under isoflurane, so these findings are expected. While not statistically significant, both PolyHb groups ended the experimental protocol with lower pO 2 than control groups, possibly due to pulmonary vasoconstriction, a known consequence of HBOC transfusion that can be alleviated with inhaled NO, or due to the enhanced lung neutrophil activity observed (Figure F,G).…”

Section: Discussionmentioning

confidence: 88%

Polymerized Hemoglobin With Increased Molecular Size Reduces Toxicity in Healthy Guinea Pigs

Williams

Muller

Eaker

et al. 2020

ACS Appl. Bio Mater.

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Hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have been developed as an alternative to red blood cells (RBCs) for use in transfusion medicine. HBOCs have many benefits over RBCs; however, previous generations of HBOCs failed in clinical trials due to unanticipated cardiotoxicity. These problems likely originated from vasoconstriction, hypertension, oxidative stress, and the presence of low-molecular-weight (MW) Hb species in the HBOC formulation. Therefore, the objective of this study is to compare the toxicity of small-MW Polymerized bovine Hb (SPolyHb) to large-MW Polymerized bovine Hb (LPolyHb) in guinea pigs, since they lack the ability to synthesize vitamin C and are more sensitive to oxidative stress than other preclinical animal models. The two PolyHbs used in this study have similar molecular diameters (72 and 69 nm, respectively), but the SPolyHb included approximately 15% Hb polymers with MW below 256 kDa, which were significantly removed from LPolyHb. Solutions were injected as a hypervolemic (topload) infusion of 10% of the blood volume into animals. SPolyHb caused a 50% elevation in mean arterial pressure (MAP) from the baseline, while LPolyHb caused only a small increase in MAP. Both PolyHbs also increased markers of organ damage and tissue and systemic inflammation compared to controls. SPolyHb caused significant changes in tissue function and vital organ toxicity markers compared to LPolyHb, specifically markers related to kidney, liver, and lung injury and systemic inflammation and iron transport by the reticuloendothelial system. LPolyHb had a longer half-life than SPolyHb, which correlates with observations made in the reticuloendothelial and iron transport systems. These studies indicate that the molecular size of PolyHb determines vasoactivity, circulation time, mechanism of elimination, toxicity, and inflammation induced by its infusion.

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Section: Discussionmentioning

confidence: 88%

Polymerized Hemoglobin With Increased Molecular Size Reduces Toxicity in Healthy Guinea Pigs

Williams

Muller

Eaker

et al. 2020

ACS Appl. Bio Mater.

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“…Inhaled NO can prevent the systemic vasoconstriction induced by infusion of HBOCs in these mice with endothelial dysfunction. In a case report, Marrazzo and colleagues described an 87‐year‐old patient with acute life‐threatening anaemia (Hb level at 40 g·L −1 ) (Marrazzo et al ., 2018). This patient had a history of an anti‐Jk3 alloantibody and could only receive packed red blood cells lacking the Jk3 antigen, which is an extremely rare phenotype in most populations.…”

Section: Inhaled No In Haemolysismentioning

confidence: 99%

Inhaled nitric oxide

Ichinose

Bloch

et al. 2018

British J Pharmacology

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Nitric oxide (NO) is a gas that induces relaxation of smooth muscle cells in the vasculature. Because NO reacts with oxyhaemoglobin with high affinity, the gas is rapidly scavenged by oxyhaemoglobin in red blood cells and the vasodilating effects of inhaled NO are limited to ventilated regions in the lung. NO therefore has the unique ability to induce pulmonary vasodilatation specifically in the portions of the lung with adequate ventilation, thereby improving oxygenation of blood and decreasing intrapulmonary right to left shunting. Inhaled NO is used to treat a spectrum of cardiopulmonary conditions, including pulmonary hypertension in children and adults. However, the widespread use of inhaled NO is limited by logistical and financial barriers. We have designed, developed and tested a simple and economic NO generation device, which uses pulsed electrical discharges in air to produce therapeutic levels of NO that can be used for inhalation therapy. Linked Articles This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc

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“… 120 To mitigate this effect, a variety of strategies have been clinically suggested, for instance, employing inhaled NO during HBOCs infusion, and antihypertensive therapies have been suggested to mitigate this effect. 121 …”

Section: Discussionmentioning

confidence: 99%

Tracking Research on Hemoglobin-Based Oxygen Carriers: A Scientometric Analysis and In-Depth Review

Zhang,

Ma,

Dai

et al. 2023

DDDT

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Numerous studies on the formulation and clinical applications of novel hemoglobin-based oxygen carriers (HBOCs) are reported in the scientific literature. However, there are fewer scientometric analysis related to HBOCs. Here, we illustrate recent studies on HBOCs using both a scientometric analysis approach and a scope review method. We used the former to investigate research on HBOCs from 1991 to 2022, exploring the current hotspots and research trends, and then we comprehensively analyzed the relationship between concepts based on the keyword analysis. The evolution of research fields, knowledge structures, and research topics in which HBOCs located are revealed by scientometric analysis. The elucidation of type, acting mechanism, potential clinical practice, and adverse effects of HBOCs helps to clarify the prospects of this biological agent. Scientometrics analyzed 1034 publications in this research field, and these findings provide a promising roadmap for further study.

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Inhaled nitric oxide prevents systemic and pulmonary vasoconstriction due to hemoglobin-based oxygen carrier infusion: A case report

Cited by 11 publications

References 13 publications

Polymerized Hemoglobin With Increased Molecular Size Reduces Toxicity in Healthy Guinea Pigs

Polymerized Hemoglobin With Increased Molecular Size Reduces Toxicity in Healthy Guinea Pigs

Inhaled nitric oxide

Tracking Research on Hemoglobin-Based Oxygen Carriers: A Scientometric Analysis and In-Depth Review

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