Comparison of Melatonin, Hypertonic Saline, and Hydroxyethyl Starch for Resuscitation of Secondary Intra-Abdominal Hypertension in an Animal Model

Abstract

A variety of agents may have a beneficial effect in reducing injury-induced intestinal edema of fluid, but studies confirming the efficacy and mechanisms of these agents in secondary intra-abdominal hypertension (IAH) are lacking. This study was to compare the effectiveness of melatonin, 7.5% hypertonic saline (HS), and hydroxyethyl starch 130/0.4 (HES) on the resuscitation of secondary IAH in a rat model. Female SD rats were divided into: sham group, shock group, lactated Ringer solution (LR) group, melatonin group, HS group, and HES group. Except for the sham group, all rats underwent a combination of inducing portal hypertension, hemorrhaging to a MAP of 40 mmHg for 2 hr, and using an abdominal restraint device. The collected blood was reinfused and the rats were treated with LR (30ml/h), melatonin (50 mg/kg) + LR, HS (6 ml/kg) + LR, and HES (30 ml/kg) + LR, respectively. The shock group received no fluids. LR was continuously infused for 6hr. The intestinal permeability, immunofluorescence of tight junction proteins, transmission electron microscopy, level of inflammatory mediators (TNF-a, IL-1β, IL-6) and of biochemical markers of oxidative stress (malondialdehyde, myeloperoxidase activity, and glutathione peroxidase) were assessed. Expressions of the protein kinase B (Akt) and of tight junction proteins were detected by Western blot. Compared with LR, HS, and HES, melatonin was associated with less inflammatory and oxidative injury, less intestinal permeability and injury, and lower incidence of secondary IAH in this model. The salutary effect of melatonin in this model was associated with the upregulation of intestinal Akt phosphorylation.

Effects of Hypertonic Saline and Hydroxyethyl Starch on Myeloid-Derived Suppressor Cells in Hemorrhagic Shock Mice under Secondary Bacterial Attack

“…The other studies based on different animal models present that HTS and HES both could block the increase of TNF-α, IL-1β, IL-6, or GM-CSF. Research on burn mouse model shows that resuscitation with HTS could augment NF-κB, TLR4, MyD88, and pp38 expressions, decrease the apoptosis of inflammatory cells, and enhance bacterial clearance and bacterial killing activities [5,9,30,33,35,36,[40][41][42][43][44]. Resuscitation with HES also exhibits an anti-inflammatory effect in the intestinal injury after hemorrhagic shock, by dropping TNF-α, IL-6 expressions, and NF-κB activation in ileum.…”

“…The pharmacokinetics also shows that HES would be no residual 24 hours after resuscitation. Except the hemodynamic properties, HTS and HES both have other effects [5,11,32]. HTS can reduce endothelial and tissue edema, improve microcirculation, inhibit the expression of adhesion molecule in endothelial cells, suppress the activation of neutrophil, alter inflammatory cytokine production, and attenuate oxidative stress [33][34][35].…”

“…In the hemorrhagic shock therapy, fluid resuscitation is a core stone. The crystalloid solutions like normal saline (NS), hypertonic saline (HTS), and the colloidal solution hydroxyethyl starch (HES) are the most commonly used in clinic and research [5,6]. Besides the improvement in hemodynamic parameters, studies have also found the regulating effect of HTS and HES in systemic inflammation responses after hemorrhagic shock [7][8][9][10][11].…”

An Ingestible Electronics for Continuous and Real-Time Intraabdominal Pressure Monitoring

“…The PDT addresses the major shortcomings of the current intravesical monitoring system, including the inability to archive continuous data, wasted manpower, and the induced vulnerability to urinary tract infection. Several animal models were developed to create intrabdominal hypertension [ 36 , 37 , 38 , 39 , 40 ]. In order to develop the adjustable intraabdominal pressure environment, we used a porcine model with inducing pneumoperitoneum with a carbon dioxide insufflator.…”

Distribution and differentiation of myeloid-derived suppressor cells after fluid resuscitation in mice with hemorrhagic shock

“…Studies based on different animal models suggest that HTS and HES could either directly or indirectly alter the expression of cytokines and activation of signaling pathways, including those above (Coimbra et al, 1996;Loomis et al, 2001;Ke et al, 2006;Wang et al, 2009;Chen et al, 2013;Esnault et al, 2013;Liu et al, 2013;Choi et al, 2014;Dong et al, 2014;Huang et al, 2014;Igarashi et al, 2014;Wright et al, 2014;Öztürk et al, 2015;Chang et al, 2016). Thus, the MDSC-related cytokines and signaling pathways in hemorrhagic shock resuscitation with different kinds of fluids need further research.…”