Novel high molecular weight polymerized hemoglobin in a non-obese model of cardiovascular and metabolic dysfunction

Cynthia R. Muller; Alexander T. Williams; Allyn M. Eaker; Cynthia Walser; Fernando Dos Santos; Clayton T. Cuddington; Savannah R. Wolfe; Andre F. Palmer; Pedro Cabrales

Biomedicine & Pharmacotherapy (Jul 2024)

Novel high molecular weight polymerized hemoglobin in a non-obese model of cardiovascular and metabolic dysfunction

Cynthia R. Muller,
Alexander T. Williams,
Allyn M. Eaker,
Cynthia Walser,
Fernando Dos Santos,
Clayton T. Cuddington,
Savannah R. Wolfe,
Andre F. Palmer,
Pedro Cabrales

Affiliations

Cynthia R. Muller: Department of Bioengineering, University of California, San Diego, CA, USA
Alexander T. Williams: Department of Bioengineering, University of California, San Diego, CA, USA
Allyn M. Eaker: Department of Bioengineering, University of California, San Diego, CA, USA
Cynthia Walser: Department of Bioengineering, University of California, San Diego, CA, USA
Fernando Dos Santos: Department of Anesthesiology & Critical Care, University of California, San Diego, CA, USA
Clayton T. Cuddington: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA
Savannah R. Wolfe: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA
Andre F. Palmer: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA
Pedro Cabrales: Department of Bioengineering, University of California, San Diego, CA, USA; Correspondence to: University of California, San Diego, Department of Bioengineering, 9500 Gilman Dr. La Jolla, San Diego, CA 92093-0412, USA.

Journal volume & issue: Vol. 176
p. 116789

Abstract

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The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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