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Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and/or oxidative events. Materials and methods: Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40 min, followed by 75 mL/kg/h) with Ringer&rsquo, s solution (n = 8/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. Results: Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 &plusmn, 420 vs. 724 &plusmn, 75 AU) and in liver (474 &plusmn, 57 vs. 261 &plusmn, 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p &lt, 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 &plusmn, 2 vs. 14 &plusmn, 0.5 RLU). Conclusion: Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and/or oxidative stress reactions.

Background Blood loss and resuscitation after trauma are associated with decreased hematocrit and hypoxia. Previously we showed that nitric oxide (NO) supplemented resuscitation (Sobhian et al., Am. J. Surg. (2011)), despite a transient decrease in mean arterial pressure, significantly enhanced perfusion in various organs with a strong trend to improve survival. Recently nitrite was identified as a potent NO-source under hypoxia. The aim of this study was to investigate the hemodynamic effects of nitrite under hypoxic conditions in a volume replacement model in rats. Methods Anesthetized rats were bled (0.5 min/ml) and Ringer’s solution was infused simultaneously (1.5 ml/min) to reduce hematocrit from 41 ± 2% to 20 ± 2%. Animals were randomly assigned to normoxia (NOX, PO2 > 80 mm Hg) or hypoxia (HOX, PO2 approx. 55 mm Hg). Hypoxia was induced by inhalation of nitrogen/air containing 15% O2. After 10 min of hypoxia or equal normoxic period, animals received a bolus dose of nitrite (15 μmol/kg). At given time points blood samples were taken for blood gas analysis and determination of NO–hemoglobin (NO–Hb) complexes. Hemodynamic parameters were determined by pulse wave analysis. Peripheral perfusion in the skin was analysed by laser Doppler imaging. Results Hypoxia led to a significant decrease in arterial pO2 (132.1 ± 7.0 vs. 58.9 ± 5.1 mm Hg) and SO2 (95.4 ± 0.4 vs. 69.1 ± 4.9%). Nitrite-derived NO assessed as NO–Hb complexes by electron paramagnetic resonance spectroscopy was 3.5 times higher in HOX compared to NOX group nitrite injection led to an immediate drop in mean arterial pressure (MAP) in both groups. While this was transient in the NOX group, in the HOX group MAP stayed significantly reduced until end ob observation (P Conclusion Similar to NO-supplemented resuscitation, nitrite under hypoxic conditions decreased MAP but increased peripheral perfusion. Additional studies will determine the impact on short-and long-term survival. Supported by FWF grant P21121. Disclosure Supported by FWF Grant P21121.

Nitric oxide (NO) released from nitrite under low oxygen tension may improve tissue perfusion and attenuate hypoxia induced injury due to its vasodilatory effect. We aimed to investigate the hemodynamic effects of nitrite under hypoxic and normoxic conditions in vivo. Anesthetized rats were bled and Ringer’s solution was infused simultaneously to reduce hematocrit to 20 ± 2%. Animals were randomly assigned to normoxia (NOX, pO2 >80 mmHg) or hypoxia (HOX, pO2 ∼55 mmHg). Hypoxia was induced by inhalation of nitrogen/air containing 15% O2. After 10 min of hypoxia or normoxia, animals received a bolus dose of nitrite (15 μmol/kg) resulting in an immediate drop in mean arterial blood pressure (MAP). Nitrite-derived NO assessed as NO–hemoglobin complex (NO–Hb) by electron paramagnetic resonance spectroscopy was 3.5 times higher in HOX compared to NOX group. Despite higher NO–Hb levels in HOX group, MAP response did not differ between groups (HOX 9.5 ± 1.9 vs. NOX 8.4 ± 3.3 mmHg). Similarly, vascular tone assessed by reflection index of pulse wave did not differ (HOX 71.5 ± 12.3 vs. NOX 82.1 ± 12.4). An increase in nitrite up to 50 μmol/kg resulted in further decrease in MAP suggesting that nitrite reduction had not reached a steady state level. Our results suggest that (i) nitrite mediated vasodilation is mediated by NO release from parenchymal rather than from red blood cells, (ii) oxygen tension in parenchymal cells under normoxic conditions is low enough to reduce nitrite to NO augmenting hemodynamic and vascular response similar to hypoxia. FWF grant P21121.