Background/Aims: Cross-linked hemoglobin (XL-Hb), a hemoglobin-based oxygen
carrier, is currently under investigation as a blood substitute. In the pr
esent study we have evaluated its presser and renal effects in a rat model
of liver cirrhosis by bile duct ligation,
Methods: Experiments were performed 3 weeks after surgery in anesthetized r
ats. In the first protocol, the ability of XL-Hb to recover blood pressure
after a hypotensive hemorrhage (0.5 ml/min, 10 min) was analyzed. In the se
cond protocol, the presser-and renal effects produced by the administration
of XL-Hb were evaluated during a period of 3 h,
Results: After a hypotensive hemorrhage (0.5 ml/min, 10 min), resuscitation
with XL-Hb resulted in greater and faster recovery of blood pressure than
with the administration of blood. In non-hemorrhaged rats, administration o
f XL-Hb (5% of blood volume) reversibly increased blood pressure in bile du
ct ligation and in control rats, but this effect was of longer duration in
the control animals. XL-Hb also induced brisk increases in water and sodium
excretion in both groups of animals, but the response of the control anima
ls was more intense and sustained than that of the bile duct ligation rats.
Glomerular filtration rate and renal blood flow showed slight decreases, b
ut they were well maintained around the baseline levels, All the parameters
studied were normalized 3 h later. In additional experiments, the effect o
f a bolus of L-NAME (10 mg/kg), au inhibitor of nitric oxide synthase, 1 h
after the administration of XII-Hb was partially reduced, suggesting that t
he effect of XL-Hb may be secondary to the disappearance of circulating nit
ric oxide.
Conclusions: XL-Hb seems to be effective as a resuscitative solution in cas
e of hemorrhage in cirrhotic rats. Moreover, this blood substitute only mod
erately and reversibly elevates blood pressure and does not adversely affec
ts renal function.