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.
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.
Valeri
C Robert
CR
Naval Blood Research Laboratory, 195 Bournehurst Drive, Plymouth, MA 02360, USA. navblood@nbrl.org
Ragno
Gina
G
Veech
Richard L
RL
D000818:Animals; D001802:Blood Substitutes / Q000009:adverse effects*; D005079:Excipients / Q000009:adverse effects*; D005440:Fluid Therapy; D006801:Humans; D007552:Isotonic Solutions / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D000077325:Ringer's Lactate; D000077331:Ringer's Solution
D001802:Blood Substitutes; D005079:Excipients; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D000077331:Ringer's Solution