Pressor and renal effects of cross-linked hemoglobin in anesthetized cirrhotic rats

Background/Aims: Cross-linked hemoglobin (XL-Hb), a hemoglobin-based oxygen carrier, is currently under investigation as a blood substitute. In the present study we have evaluated its pressor and renal effects in a rat model of liver cirrhosis by bile duct ligation. Methods: Experiments were performed 3 weeks after surgery in anesthetized rats. 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 second protocol, the pressor 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 of XL-Hb (5% of blood volume) reversibly increased blood pressure in bile duct 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 animals was more intense and sustained than that of the bile duct ligation rats. Glomerular filtration rate and renal blood flow showed slight decreases, but they were well maintained around the baseline levels. All the parameters studied were normalized 3 h later. In additional experiments, the effect of a bolus of L-NAME (10 mg/kg), an inhibitor of nitric oxide synthase, 1 h after the administration of XL-Hb was partially reduced, suggesting that the effect of XL-Hb may be secondary to the disappearance of circulating nitric oxide. Conclusions: XL-Hb seems to be effective as a resuscitative solution in case of hemorrhage in cirrhotic rats. Moreover, this blood substitute only moderately and reversibly elevates blood pressure and does not adversely affects renal function.