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.
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