Hypotensive effects of stroma-free haemoglobin solutions attributable to adenine nucleotides.
Aqueous solutions of stroma-free human haemoglobin are being evaluated as potential oxygen-carrying resuscitation fluids. There are indications, however, that such solutions may produce toxic side-effects in vivo. Stroma-free haemoglobin solution produced a 50% fall in mean arterial pressure when infused into a small animal model despite containing very low levels of non-haem protein and phospholipid contaminants. This effect was not produced by haemoglobin solutions after extensive dialysis. Red cell-derived adenine nucleotides were found to be present in concentrations high enough to cause such a response (80-85 micrograms/ml). We have developed a chromatographic assay capable of predicting hypotension in our animal model and consider that the complete absence of adenine nucleotides must be confirmed in all studies concerning the possible toxic side-effects of stroma-free haemoglobin solutions.
MacDonald
S L
SL
Scottish National Blood Transfusion Service, Headquarters Unit Laboratory, Edinburgh, UK.
McLaughlin
L F
LF
MacGregor
I R
IR
Pepper
D S
DS
D000227:Adenine Nucleotides / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002853:Chromatography, Liquid; D004340:Drug Contamination; D004731:Endotoxins / Q000032:analysis; D005260:Female; D006454:Hemoglobins / Q000633:toxicity*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D008033:Limulus Test; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions
D000227:Adenine Nucleotides; D004731:Endotoxins; D006454:Hemoglobins; D010743:Phospholipids; D012996:Solutions; D000255:Adenosine Triphosphate