Damage control immunoregulation: is there a role for low-volume hypertonic saline resuscitation in patients managed with damage control surgery?

Hypertonic saline (HTS) is beneficial in the treatment of head-injured patients as a result of its potent cytoprotective effects on various cell lines. We hypothesize that low-volume resuscitation with 3 per cent HTS, when used after damage control surgery (DCS), improves outcomes compared with standard resuscitation with isotonic crystalloid solution (ICS). This is a 4-year retrospective review from two Level I trauma centers. Patients included had 10 units or more of packed red blood cells during initial DCS. On arrival to the trauma intensive care unit (TICU), patients were resuscitated with low-volume 3 per cent HTS or with conventional ICS. A cohort analysis was performed comparing resuscitation strategies. Univariate analysis of continuous data was done with Student t test followed by multivariate analysis. Of 188 patients included, 76 were in the low-volume HTS group and 112 in the ICS group. Demographics were similar between the groups. Over the next 48 hours after DCS in HTS versus ISC groups, intravenous fluids were given: 1920 ± 455 mL versus 8400 ± 1200 mL (P < 0.0001); urine output was 4320 ± 480 mL versus 1940 ± 480 mL(P < 0.0001); mean TICU length of stay was 10 ± 8 versus 16 ± 15 days (P < 0.01); prevalence of acute respiratory distress syndrome was 4.0 versus 13.4 per cent (P = 0.02); sepsis was 6.6 versus 15.2 per cent (P = 0.06); multisystem organ failure was: 2.6 versus 16.1 per cent (P < 0.01); and 30-day mortality was 5.3 versus 15.2 per cent (P = 0.03). There was no difference for prevalence of renal failure at 5.3 versus 3.6 per cent (P = 0.58). Low-volume resuscitation with HTS administered after DCS on arrival to the TICU may have a protective effect on the polytrauma patient. We believe that this study demonstrates a role for low-volume resuscitation with HTS to improve outcomes in patients undergoing DCS.

Modeling withdrawal syndrome in zebrafish.

The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscience research. Zebrafish behavior is robustly affected by environmental and pharmacological manipulations, and can be examined using exploration-based paradigms, paralleled by analysis of endocrine (cortisol) stress responses. Discontinuation of various psychotropic drugs evokes withdrawal in both humans and rodents, characterized by increased anxiety. Sensitivity of zebrafish to drugs of abuse has been recently reported in the literature. Here we examine the effects of ethanol, diazepam, morphine and caffeine withdrawal on zebrafish behavior. Overall, discontinuation of ethanol, diazepam and morphine produced anxiogenic-like behavioral or endocrine responses, demonstrating the utility of zebrafish in translational research of withdrawal syndrome.

Analyzing habituation responses to novelty in zebrafish (Danio rerio).

Analysis of habituation is widely used to characterize animal cognitive phenotypes and their modulation. Although zebrafish (Danio rerio) are increasingly utilized in neurobehavioral research, their habituation responses have not been extensively investigated. Utilizing the novel tank test, we examine intra- and inter-session habituation and demonstrate robust habituation responses in adult zebrafish. Analyzing the intra-session habituation to novelty further, we also show that selected anxiogenic drugs (caffeine, pentylenetetrazole), as well as stress-inducing alarm pheromone, attenuated zebrafish habituation. Some acute anxiolytic agents, such as morphine and ethanol, while predictably reducing zebrafish anxiety, had no effects on habituation. Chronic ethanol and fluoxetine treatments improved intra-session habituation in zebrafish. In general, our study parallels literature on rodent habituation responses to novelty, and reconfirms zebrafish as a promising model for cognitive neurobehavioral research.

Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish.

The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.