-transparent.png){kind=logo}
Aqueous human hemoglobin is being considered as an oxygen-transporting resuscitation solution. However, there are some indications that such solutions may be toxic. We report here that at a clinically significant dose (20% to 30% of the estimated blood volume) of hemoglobin solution (10 gm/dl), toxicity similar to that reported in humans is produced in rabbits. This toxicity is characterized by cardiac rhythm disturbances (25%) and coagulation abnormalities, manifested as intravascular thrombi. Hypoxia, tissue necrosis (brain 29%, liver 25%), and death (22%) were seen. Hypoxia appears to be the cause of death, because the arterial PO2 of rabbits that died was significantly lower (43 +/- 8 mm Hg) than that of rabbits that lived (80 +/- 12 mm Hg). We also report the effect of the method of preparation or degree of purity on the observed toxicity. Stroma-free red blood cell hemolysate, stroma-free hemoglobin, zinc-precipitated hemoglobin, and chromatographically purified hemoglobin were infused. Purification of these solutions ranged from removal of stroma to removal of all detectable nonhemoglobin protein components. In addition, the nonhemoglobin proteins were concentrated and infused into rabbits to compare their effects. All of these hemoglobin solutions induced similar toxicity for rabbits infused with stroma-free hemoglobin. The nonhemoglobin proteins, as well as human serum albumin, exhibited no toxicity. These results demonstrate that, at the clinically relevant dose, hemoglobin or something inherently associated with hemoglobin is toxic.
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
December 1990,
Anesthesia and analgesia,
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
March 1989,
Indian journal of experimental biology,
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
September 1974,
Canadian journal of surgery. Journal canadien de chirurgie,
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
March 1987,
Archives of surgery (Chicago, Ill. : 1960),
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
September 1973,
Polski tygodnik lekarski (Warsaw, Poland : 1960),
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
June 1968,
The Journal of biological chemistry,
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
January 1974,
Comptes rendus des seances de la Societe de biologie et de ses filiales,
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
November 1989,
The Journal of surgical research,
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
January 1984,
Hypertension (Dallas, Tex. : 1979),
C T White, and
A J Murray, and
J R Greene, and
D J Smith, and
F Medina, and
G T Makovec, and
E J Martin, and
R B Bolin
July 1985,
Thrombosis research,
