Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits

Caron, Alexis; Menu, Patrick; Faivre-Fiorina, Béatrice; Labrude, Pierre; Alayash, Abdu I.; Vigneron, C.

doi:10.1152/jappl.1999.86.2.541

Cited by 33 publications

(22 citation statements)

References 24 publications

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“…Predictions of the effect of HBOC cooperativity on Pv O 2 for humans. Figure 6 shows the mixed Pv O 2 for a mixture of RBCs and HBOC for varying HBOC cooperativity and for three different values of P 50 .…”

Section: Equationmentioning

confidence: 99%

“…A quantitative understanding of oxygen transport parameters in the presence of HBOCs could guide the design of HBOCs to provide oxygen delivery to tissue for a desired clinical application. The oxygen transport parameters of HBOCs or RBCs are characterized by the oxygen-hemoglobin equilibrium dissociation curve (ODC) that describes the fractional hemoglobin saturation as a function of PO 2 .…”

mentioning

confidence: 99%

“…In vivo experimental studies on several species such as cat, hamster, and pig with a wide range of HBOC oxygen transport parameters have been performed (2,7,8,22). Experimental studies have demonstrated that HBOCs can improve tissue oxygenation.…”

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confidence: 99%

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Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport

Kavdia

Pittman

Popel

2002

Journal of Applied Physiology

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Kavdia, Mahendra, Roland N. Pittman, and Aleksander S. Popel. Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport. J Appl Physiol 93: 2122-2128, 2002. First published September 6, 2002 10.1152 10. /japplphysiol.00676.2002 O 2 carriers (HBOCs), which are developed as an alternative to blood transfusion, provide O 2 delivery. At present, there is no model to predict the O 2 transport for a red blood cell-HBOC mixture on a whole organ basis. On the basis of the first principles of mass balance, a model of O 2 transport for an organ was derived to calculate venous PO 2 (PvO 2 ) for a given inlet arterial PO 2 (PaO 2 ), blood flow, and oxygen consumption. The model was validated by using several in vivo animal studies on HBOC administration for a wide range of HBOC oxygen-binding parameters and predicted Pv O 2 for various Pa O 2 in the same species. The model was also used to predict the effect of HBOC affinity and cooperativity on Pv O 2 for humans. The results indicate that PvO 2 can be increased at a constant blood flow-to-oxygen consumption ratio by reducing the affinity of HBOC for normoxia and mild hypoxia; however, a high-affinity HBOC would be more efficient in maintaining higher Pv O 2 for severe hypoxia (PaO 2 Ͻ 40 Torr).hemoglobin based oxygen carrier; oxygen affinity; exchange transfusion; partial pressure of oxygen at 50% hemoglobin saturation; oxygen dissociation curve; cat; hamster

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Section: Equationmentioning

confidence: 99%

mentioning

confidence: 99%

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Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport

Kavdia

Pittman

Popel

2002

Journal of Applied Physiology

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“…Animal studies suggest that these effects are due to interference with NO 14 . Additional animal work suggests that HemoLink has hemodynamic effects similar to those associated with -cross-linked hemoglobin 15 . A glutaraldehyde-polymerized bovine Hb product (Hemopure or HBOC-201, Biopure Corporation, Cambridge, MA, USA) has a reduced O 2 affinity that promotes O 2 unloading in the tissues.…”

Section: Hemoglobin Solutionsmentioning

confidence: 99%

Transfusion Alternatives in Trauma

Biffl

Moore

1999

Transfus Alt Transfus Med

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SUMMARY Restoration of oxygen‐carrying capacity plays an essential role in the management of trauma patients. The potential risks associated with allogeneic blood, as well as the immunosuppressive potential of transfusions, have stimulated interest in alternatives to allogeneic blood transfusion. In the setting of trauma, the feasible alternatives are limited to autotransfusion and blood substitutes. Autotransfusion avoids infectious risks and obviates compatibility testing. However, coagulopathy remains a significant problem associated with autotransfusion. Hemoglobin substitutes offer many theoretical advantages over allogeneic transfusion. Several formulations have been investigated in clinical trials. Our experience has been exclusively with a polymerized, pyridoxylated stroma‐free human hemoglobin‐based solution (PolyHeme). In infusions up to 10 units (5 liters) PolyHeme has proved an adequate oxygen carrier without serious adverse effects, and has reduced the need for allogeneic blood. Given its safety, efficacy, and favorable immunomodulatory profile, PolyHeme appears to have tremendous potential as an alternative to transfusion.

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“…A number of published studies have modeled the complex interrelationship of HBOCs on O 2 delivery (6,18,21), wall shear stress (22), NO scavenging (23), and altered plasma rheology (7). It is clear from these studies that a precise quantitative assessment of Hb extravasation and HBOC-induced changes in vascular permeability is fundamentally important toward understanding their intravascular behavior and oxygen delivery potential.…”

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confidence: 99%

Quantitative assessment of hemoglobin-induced endothelial barrier dysfunction

Dull

DeWitt

Dinavahi

et al. 2004

Journal of Applied Physiology

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ticelli. Quantitative assessment of hemoglobin-induced endothelial barrier dysfunction. J Appl Physiol 97: 1930 -1937, 2004. First published July 23, 2004 doi:10.1152/japplphysiol.00102.2004.-Hemoglobin (Hb)-based O 2 carriers (HBOC) are undergoing extensive development as potential "blood substitutes." A major problem associated with these molecules is an increase in microvascular permeability and peripheral vascular resistance. In this paper, we utilized bovine lung microvascular endothelial cell monolayers and simultaneously measured Hb-induced changes in transendothelial electrical resistance, diffusive albumin permeability, and diffusive Hb permeability (P DH) for three forms of Hb: natural tetrameric human Hb-A and two polymerized recombinant HBOCs containing ␣-human and ␤-bovine chains designated Hb-Polytaur (molecular mass: 500 kDa) and Hb-(Polytaur) n (molecular mass: ϳ1,000,000 Da), respectively. Hb-Polytaur and Hb-(Polytaur)n are being evaluated for clinical use as HBOCs. All three Hb molecules induce a rapid decline of transendothelial electrical resistance to 30% of baseline. Diffusive albumin permeabiltiy increases, on average, approximately ninefold (2.78 ϫ 10 Ϫ7 vs. 2.47 ϫ 10 Ϫ6 cm/s) in response to Hb exposure. All three Hb molecules induce an increase in their own permeability, a process that we have called Hb-induced Hb permeability. The magnitude of change of P DH is also related to Hb size. When PDH is corrected for the diffusive coefficient for each Hb species, no evidence of restricted diffusion is found. Immunofluorescent images demonstrate Hb-induced actin stress fiber formation and large intercellular gaps. These data provide the first quantitative assessment of the effect of polymerized HBOC on their own diffusion rates over time. We discuss the importance of these findings in terms of Hb extravasation rates, molecular sieving, and clinical consequences of HBOC use.albumin; blood substitutes; restricted diffusion HEMOGLOBIN (HB)-BASED O 2 carriers (HBOC) have received considerable attention as blood substitutes, and interest in developing these therapeutic macromolecules remains high, given the shortage and limited shelf-life of banked red blood cells, infection concerns, and, at times, unacceptable delays in crossmatching banked blood (1,24,26,33). Unfortunately, a number of unexpected problems have been associated with the use of HBOC, including extravasation, vasospasm, renal toxicity, and patient death (1,24,33). The ultimate utility of HBOC is to provide adequate oxygen delivery to patients requiring immediate resuscitation, as may occur following major trauma or surgical procedures associated with large-volume blood losses. Two untoward consequences of HBOC are extravasation of the HBOC itself, which is no longer able to participate in oxygen delivery, and the associated vasoconstriction due, at least in part, to local nitric oxide (NO) scavenging. The decrease in plasma Hb and localized vasospasms in the setting of anemia may create regional hypoxia. Overcoming these issues will...

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Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits

Cited by 33 publications

References 24 publications

Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport

Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport

Transfusion Alternatives in Trauma

Quantitative assessment of hemoglobin-induced endothelial barrier dysfunction

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