Work

Effects of the Resuscitation Fluid and the Hemoglobin Based Oxygen Carrier (HBOC) Excipient on the Toxicity of the HBOC: Ringer's D,L -Lactate, Ringer's L -Lactate, and Ringer's Ketone Solutions

Year: 2006

Type: article

Abstract: Hemoglobin based oxygen carriers (HBOC) are resuspended in "excipients" consisting of Ringer's D,L-lactate containing antioxidants to prevent methemoglobin formation during storage. Investigators have reported cardiac arrhythmias following infusion of Ringer's D,L-lactate solution. Studies have shown that D-lactate stimulates human granulocytes to generate oxygen free radicals and L-lactate inhibits glycolysis. Patients receiving HBOC in Ringer's D,L-lactate excipient are also resuscitated or hemodiluted with Ringer's lactate solution. Oxygen-free radicals generated by Ringer's D,L-lactate and HBOC may oxidize nitric oxide in endothelial cells, causing the vasoconstrictor effects reported following HBOC infusion, and activate NF-kappab and the apoptotic cascade. The combination of Ringer's D,L-lactate and HBOC in Ringer's D,L-lactate excipient may be responsible for the severe adverse events observed in clinical studies of HBOC.Veech has recommended replacing the 27 mM of lactate in Ringer's with 27 mM D-betahydroxybutyrate (BHB). BHB reduces the generation of oxygen free radicals by mitochondria and human granulocytes.

Source: Artificial Cells Blood Substitutes and Biotechnology

DOI: 10.1080/10731190600974087

Authors: C. Robert Valeri, Gina Ragno, Richard L. Veech

Institution: National Institutes of Health

Language: English

Topic: Hemoglobin structure and function

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: U.S. Navy, Office of Naval Research