The effects of antioxidants on a porcine model of liver hemorrhage.

PURPOSE: The aim of this study is to assess the efficacy of the combination of N-acetylcysteine (NAC) and deferoxamine (DFO) in the resuscitation from hemorrhagic shock in a porcine model of bleeding during hepatectomy. METHODS: Twenty-one pigs were divided randomly to three groups: Sham (S) group, n = 5; fluid (F) resuscitation group, n = 8; and fluid plus NAC plus DFO (NAC&DFO) resuscitation group, n = 8. The animals of groups F and NAC&DFO were subjected to left hepatectomy and controlled hemorrhage from the traumatic liver surface. Shock was established within 10 minutes and maintained for 30 minutes at mean arterial pressure (MAP) of 30 to 40 mm Hg. Resuscitation followed the shock period with crystalloids and colloids. Group NAC&DFO received additionally NAC and DFO in doses of 200 mg/kg and 65 mg/kg, respectively. The total time of the experiment was 6 hours. RESULTS: Animal weight, blood loss, excised liver mass, and MAP at the end of the shock period were comparable between experimental groups. Group NAC&DFO received significantly lower volume of both crystalloids and colloids (35% and 42% less, respectively) compared to group F. Hepatocellular proliferation (proliferating cell nuclear antigen) was higher in the antioxidant group. Apoptosis, measured by caspase-3, was restored to sham group levels when NAC and DFO were administered. CONCLUSIONS: Our experimental study showed that coadministration of NAC and DFO during liver hemorrhage can decrease the amounts of fluids needed for resuscitation. Moreover, the antioxidant combination restores the energy dependent apoptosis and proliferation of the hepatocytes.

The effects of hemorrhagic shock secondary to hepatectomy in a swine model.

BACKGROUND: Ischemia-reperfusion injury caused by severe hemorrhagic shock and subsequent resuscitation leads to deterioration of hepatic homeostasis and possibly to liver failure. The present study focuses on determining whether there is a different biological response to hemorrhagic shock by different sources of hemorrhage, hepatic hemorrhage (HH) versus peripheral hemorrhage. METHODS: Twenty-one male swine (Sus scrofa domesticus) were randomly allocated in three groups as follows: sham group (S, n = 5), central venous hemorrhage group, (CVH) (n = 8), and HH group (n = 8). Hepatectomy of the left liver lobe was carried out in groups CVH and HH, and the animals were subjected to controlled bleeding from the internal jugular vein and the traumatic liver surface, respectively. After 10 min of hemorrhage, shock was maintained for 30 min at mean arterial pressure levels of 30 mm Hg-40 mm Hg and resuscitation was initiated with crystalloids and colloids. Hemodynamic parameters and fluid balance were monitored throughout the 6 h of total duration of the experiment. Blood samples were collected at 0-, 40-, and 360-min time points for transaminases, albumin, and interleukin-6 measurement. Hepatic tissue was harvested at the end of the experiment for oxidative marker and proliferation analysis. RESULTS: Although blood loss was comparable between the two groups, the amount of fluids needed for resuscitation was higher for the HH group. Inflammatory response, measured by interleukin-6, was found higher in HH group. Oxidative stress markers did not reveal statistically significant difference between the two groups. Liver hemorrhage decreased hepatocellular proliferation measured by proliferating cell nuclear antigen. CONCLUSIONS: Our study provides evidence that HH entails worse consequences for the hepatocytes than systemic hemorrhage. Higher needs for resuscitation fluids, decreased proliferation, and augmented inflammatory response when HH takes place are findings with possible clinical importance in liver surgery and trauma.

Resuscitation after hemorrhagic shock: the effect on the liver--a review of experimental data.

The liver is currently considered to be one of the first organs to be subjected to the hypoxic insult inflicted by hemorrhagic shock. The oxidative injury caused by resuscitation also targets the liver and can lead to malfunction and the eventual failure of this organ. Each of the various fluids, vasoactive drugs, and pharmacologic substances used for resuscitation has its own distinct effect(s) on the liver, and the anesthetic agents used during surgical resuscitation also have an impact on hepatocytes. The aim of our study was to identify the specific effect of these substances on the liver. To this end, we conducted a literature search of MEDLINE for all types of articles published in English, with a focus on articles published in the last 12 years. Our search terms were "hemorrhagic shock," "liver," "resuscitation," "vasopressors," and "anesthesia." Experimental studies form the majority of articles found in bibliographic databases. The effect of a specific resuscitation agent on the liver is assessed mainly by measuring apoptotic pathway regulators and inflammation-induced indicators. Apart from a wide range of pharmacological substances, modifications of Ringer's Lactate, colloids, and pyruvate provide protection to the liver after hemorrhage and resuscitation. In this setting, it is of paramount importance that the treating physician recognize those agents that may attenuate liver injury and avoid using those which inflict additional damage.