Pressor and renal effects of cross-linked hemoglobin in anesthetized cirrhotic rats
Section snippets
Materials and Methods
All the experiments were conducted following the European Union guidelines for the ethical treatment of animals. Male Sprague-Dawley rats, born and raised in the Animalario of the Universidad de Murcia, were used in the present study. Bile duct ligation (BDL) was performed in rats weighing 225–275 g, following a method previously described 19., 20., 21.. In brief, the animals were anesthetized with ethylic ether and, under aseptic techniques, subjected to BDL and excision or simulated operation
Protocol 1. Comparison of pressor effects of XL-Hb and blood
Fig. 1 shows the MAP response to the reinfusion of blood or XL-Hb in control and cirrhotic rats. MAP was always lower in the BDL animals (96.1±2.5 mmHg) than in the controls (116.5±3.6). In the control animals, the hemorrhage decreased MAP to 59.3±2.9 and the reinfusion of blood slowly returned it to the control values, reaching a maximum of 121.3±5.0 8 min later. In contrast, the infusion of XL-Hb elevated MAP faster and to higher values, reaching a maximum of 138.0±9.4 at the third minute.
Discussion
In the present study, we have evaluated the effects of a blood substitute, the cross-linked hemoglobin, in a rat model of liver cirrhosis to assess its efficacy in restoring blood pressure after a hypotensive hemorrhage. Replacing lost blood with hemoglobin has the advantage of simultaneous scavenging of nitric oxide (22), which is implicated in the induction of endotoxic shock. In the first series of experiments, XL-Hb proved useful as a tool to recover blood pressure after an important acute
Acknowledgements
This study was supported by Spanish Government grants SAF95-1549-C02-02 and SAF97-0176 from the Comisión Interministerial de Ciencia y Tecnología. During the period of this study, M.C.O. (FP94-29000129) and L.A.F. (PN95-42849602) were recipients of a predoctoral fellowship from the Ministerio de Educación y Cultura of Spain.
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Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment
2010, Toxicology and Applied PharmacologyCitation Excerpt :Recently, Zapletal et al. showed that acellular type hemoglobin-based oxygen carrier (HBOC-201) attenuated the microvascular dysfunction and improved the tissue oxygenation following the ischemic reperfusion injury in liver (Zapletal et al., 2009). Furthermore, it was reported that acellular type HBOC was useful for prehospital resuscitation with uncontrolled hemorrhage due to liver injury and hepatic cirrhosis (Ortiz et al., 2000; Arnaud et al., 2008). These results suggest that HbV and acellular type HBOC are potential candidates for alternative treatment of RBCs during liver transplantation, hepatic injury and bleeding induced by hepatic cirrhosis.
Vitamin E prevents renal dysfunction induced by experimental chronic bile duct ligation
2003, Kidney InternationalCitation Excerpt :While this degree of renal vasoconstriction is well known to occur during cirrhosis (even before renal dysfunction becomes apparent) [2,56-58], it is more variable in the CBDL rats. Some studies have found decreases in RVR [32,34,44], while others have found either no change or an increase in RVR, both of which suggest renal vasoconstriction or impaired autoregulatory vasodilation [6-10,45,59,60]. The reasons for these discrepancies are not clear but may be related to subtle differences in the rat (e.g., strain, breeder, etc.), anesthesia, or the severity of the disease.
Pharmacokinetics of diaspirin cross-linked haemoglobin in a rat model of hepatic cirrhosis
2001, Journal of Pharmacy and Pharmacology