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Hypertonic saline infusion suppresses apoptosis of hippocampal cells in a rat model of cardiopulmonary resuscitation.

ABSTRACT: Hypertonic saline (HS) attenuates cerebral edema, improves microcirculation perfusion and alleviates inflammation. However, whether the beneficial effect of HS on neurological function after cardiopulmonary resuscitation (CPR) in rat model of asphyxial cardiac arrest (CA) is mediated via attenuating apoptosis of neurons is not known. We studied the neuroprotective effect of HS in rats after CA and CPR, and explored the likely underlying mechanisms. Animals were randomly assigned to 4 equal groups (n?=?15 each) according to the different infusions administered during resuscitation: control (C), normal saline (NS), hypertonic saline (HS), and hydroxyethyl starch (HES) groups. NDS at 12, 24, 48 and 72?h post-ROSC in the HS group were significantly higher than those in the NS and HES groups. Western blot analysis demonstrated a significant increase in Bcl-2 expression in HS, as compared to that in the NS and HES groups. However, Bax and Caspase-3 expressions in HS were significantly lower than that in the NS and HES groups. The apoptosis rate in HS was significantly lower than that in the NS and HES groups, suggesting HS treatment during resuscitation could effectively suppress neuronal cell apoptosis in hippocampal CA1 post-ROSC and improve neuronal function.

SUBMITTER: Zhou X

PROVIDER: S-EPMC5517425 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Hypertonic saline infusion suppresses apoptosis of hippocampal cells in a rat model of cardiopulmonary resuscitation.

Zhou Xiang X Liu Yong Y Huang Yang Y Zhu ShuiBo S Zhu Jian J Wang RongPing R

Scientific reports 20170719 1

Hypertonic saline (HS) attenuates cerebral edema, improves microcirculation perfusion and alleviates inflammation. However, whether the beneficial effect of HS on neurological function after cardiopulmonary resuscitation (CPR) in rat model of asphyxial cardiac arrest (CA) is mediated via attenuating apoptosis of neurons is not known. We studied the neuroprotective effect of HS in rats after CA and CPR, and explored the likely underlying mechanisms. Animals were randomly assigned to 4 equal group ...[more]

PMID: 28724904

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Project description:Tonicity of saline (NaCl) is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET) formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus), and bacteria (Pseudomonas aeruginosa and Staphylococcus aureus). We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12), and P. aeruginosa. Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H2O2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic solutions do not suppress NOX2-independent NETosis. Although hypertonic saline partially suppresses ionomycin-induced NETosis, it enhances A23187-induced NETosis, and it does not alter S. aureus-induced NETosis. Overall, this study determined that hypertonic saline suppresses NOX2-dependent NETosis induced by several agonists; in contrast, it has variable effects on neutrophil death induced by NOX2-independent NETosis agonists. These findings are important in understanding the regulation of NETosis and apoptosis in neutrophils.

Project description:BackgroundOur objective was to establish the safety of 3% hypertonic saline (HTS) resuscitation for trauma and acute care surgery patients undergoing emergent laparotomy and temporary abdominal closure (TAC) with the hypothesis that HTS administration would be associated with hyperosmolar hypercholoremic acidosis, lower resuscitation volumes, and higher fascial closure rates, without adversely affecting renal function.MethodsWe performed a retrospective cohort analysis of 189 trauma and acute care surgery patients who underwent emergent laparotomy and TAC, comparing patients with normal baseline renal function who received 3% HTS at 30 mL/h (n = 36) to patients with standard resuscitation (n = 153) by baseline characteristics, resuscitation parameters, and outcomes including primary fascial closure and Kidney Disease: Improving Global Outcomes stages of acute kidney injury.ResultsThe HTS and standard resuscitation groups had similar baseline illness severity and organ dysfunction, though HTS patients had lower serum creatinine at initial laparotomy (1.2 mg/dL vs. 1.4 mg/dL; p = 0.078). Forty-eight hours after TAC, HTS patients had significantly higher serum sodium (145.8 mEq/L vs. 142.2 mEq/L, p < 0.001), chloride (111.8 mEq/L vs. 106.6 mEq/L, p < 0.001), and osmolarity (305.8 mOsm/kg vs. 299.4 mOsm/kg; p = 0.006), and significantly lower arterial pH (7.34 vs. 7.38; p = 0.011). The HTS patients had lower intravenous fluid (IVF) volumes within 48 hours of TAC (8.5 L vs. 11.8 L; p = 0.004). Serum creatinine, urine output, and kidney injury were similar between groups. Fascial closure was achieved for 92% of all HTS patients and 77% of all standard resuscitation patients (p = 0.063). Considering all 189 patients, higher IVF resuscitation volumes within 48 hours of TAC were associated with decreased odds of fascial closure (odds ratio, 0.90; 95% confidence interval, 0.83-0.97; p = 0.003).ConclusionHypertonic saline resuscitation was associated with the development of a hypernatremic, hyperchloremic, hyperosmolar acidosis, and lower total IVF resuscitation volumes, without adversely affecting renal function. These findings may not be generalizable to patients with baseline renal dysfunction and susceptibility to hyperchloremic acidosis-induced kidney injury.Level of evidencePrognostic study, level II.

Project description:Abstract Objectives Mild and moderate dehydration adversely affect mood and cognitive function. During dehydration, hypertonic hypovolemia activates both osmo- and baro-receptors but it is not known which physiological pathway is associated with degraded mood state. This study examined the acute effect of osmoreceptor stimulation on mood. Methods Sixty healthy adults (50% females, 30 ± 1 y; BMI: 26.9 ± 4.0 kg·m−2) were infused intravenously with 3.0% (HYPER) or 0.9% (ISO) NaCl for 2 h (0.1 ml·kg−1·min−1) using a counterbalanced, crossover design. Blood samples were collected every 30 minutes to measure plasma osmolality (POsm), copeptin (a surrogate marker of vasopressin), and renin-angiotensin-aldosterone system (RAAS) hormones. Mood was assessed with the short version of Profile of Mood State (POMS) questionnaire before and after the infusion. Results POsm and copeptin increased from 286 ± 3 mmol·kg−1 to 305 ± 4 mmol·kg−1 and from 4.5 ± 3.7 pmol·L−1 to 20.4 ± 12.8 pmol·L−1, respectively in HYPER (P < 0.05), and were unchanged in ISO (P > 0.05). No hormonal differences were observed between trials for RAAS hormones (P > 0.05). During HYPER copeptin, following the 2-h infusion, was greater in females than in males (female: 23.4 ± 13.9 pmol·L−1, male: 17.4 ± 10.9 pmol·L−1; P < 0.05). The POMS total mood disturbance (TMD) score increased from 10.5 ± 0.9 to 16.5 ± 1.6 in HYPER (P < 0.05), but not in ISO (P > 0.05). Among POMS subscales, depression-dejection and fatigue-inertia increased in HYPER compared to ISO (P < 0.05). When TMD responses in the HYPER trial were analyzed with sex as a between-subjects factor, the increase was significant in females (pre: 10.2 ± 1.0, post: 18.6 ± 2.3; P < 0.001) but not in males (pre: 10.8 ± 1.4, post: 14.0 ± 2.0; P > 0.05). The confusion-bewilderment subscales and fatigue-inertia of the POMS were also elevated post HYPER in females (P < 0.05), but not in ISO (P > 0.05) in either sex. Conclusions Hypertonic saline infusion acutely degrades mood state, and women appear to have a more pronounced response. The underlying mechanisms remain to be determined but may be related to higher copeptin levels in women. The study was registered at ClinicalTrials.gov as NCT02761434. Funding Sources Danone Research. Supporting Tables, Images and/or Graphs

Project description:IntroductionIn series of cases and animal models suffering hemorrhagic shock, the use of vasopressors has shown potential benefits regarding hemodynamics and tissue perfusion. Terlipressin is an analogue of vasopressin with a longer half-life that can be administered by bolus injection. We have previously observed that hypertonic albumin improves resuscitation following controlled hemorrhage in piglets. The aim of the present study was to analyze whether the treatment with the combination of terlipressin and hypertonic albumin can produce better hemodynamic and tissular perfusion parameters than normal saline or hypertonic albumin alone at early stages of hemorrhagic shock in an infant animal model.MethodsExperimental, randomized animal study including 39 2-to-3-month-old piglets. Thirty minutes after controlled 30 ml/kg bleed, pigs were randomized to receive either normal saline (NS) 30 ml/kg (n = 13), 5% albumin plus 3% hypertonic saline (AHS) 15 ml/kg (n = 13) or single bolus of terlipressin 15 μg/kg i.v. plus 5% albumin plus 3% hypertonic saline 15 ml/kg (TAHS) (n = 13) over 30 minutes. Global hemodynamic and tissular perfusion parameters were compared.ResultsAfter controlled bleed a significant decrease of blood pressure, cardiac index, central venous saturation, carotid and peripheral blood flow, brain saturation and an increase of heart rate, gastric PCO2 and lactate was observed. After treatment no significant differences in most hemodynamic (cardiac index, mean arterial pressure) and perfusion parameters (lactate, gastric PCO2, brain saturation, cutaneous blood flow) were observed between the three therapeutic groups. AHS and TAHS produced higher increase in stroke volume index and carotid blood flow than NS.ConclusionsIn this pediatric animal model of hypovolemic shock, albumin plus hypertonic saline with or without terlipressin achieved similar hemodynamics and perfusion parameters than twice the volume of NS. Addition of terlipressin did not produce better results than AHS.

Project description:To investigate the effect of the occurrence of early hyperchloremia on death or severe disability at 180 days in patients with severe traumatic brain injury (TBI).DesignPost hoc analysis of Resuscitation Outcomes Consortium Hypertonic Saline (ROC HS)-TBI trial.SettingA total of 114 North American emergency medical services agencies in the ROC.PatientsA total of 991 patients with severe TBI and Glasgow Coma Scale score of less than or equal to 8.InterventionsPrehospital resuscitation with single IV dose (250 cc) of 7.5% saline in 6% dextran-70, 7.5% saline (no dextran), or crystalloid.Measurements and main resultsPatients with increased serum chloride concentrations (110 mmol/L or greater) 24 hours after randomization were identified. Hyperchloremia was graded into one or greater than or equal to 2 occurrences in the first 24 hours. Logistic regression analyses were performed to determine the effects of hyperchloremia on: 1) death or severe disability at 180 days and 2) death within 180 days after adjusting for confounders. Compared with patients without hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death or severe disability at 180 days (odds ratio [OR], 1.81; 95% CI, 1.19-2.75) and death within 180 days (OR, 1.89; 95% CI, 1.14-3.08) after adjustment for confounders. However, the total volume of fluids administered during the first 24 hours was an independent predictor of death within 180 days; therefore, after adding an interaction term between the total volume of fluids administered during the first 24 hours and greater than or equal to 2 occurrences of hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death within 180 days (OR, 2.35; 95% CI, 1.21-4.61 d) but not of composite outcome of death or severe disability at 180 days.ConclusionsAfter modifying for the effect of the total volume of fluids administered during the first 24 hours, multiple occurrences of hyperchloremia in the first 24 hours were associated with higher odds of death within 180 days in patients with severe TBI.

Project description:BackgroundIntraoperative and postoperative management of cardiac surgery patients is complex, involving the application of differential vasopressors and volume therapy. It has been shown that a positive fluid balance has a major impact on postoperative outcome. Today, the advantages and disadvantages of buffered crystalloid solutes are a topic of controversy, with no consensus being reached so far. The use of hypertonic saline (HS) has shown promising results with respect to lower total fluid balance and postoperative weight gain in critically ill patients in preliminary studies. However, collection of more data on HS in critically ill patients seems warranted. This preliminary study aims to investigate whether fluid resuscitation using HS in patients following cardiac surgery results in less total fluid volume being administered.MethodsIn a prospective double-blind randomised controlled clinical trial, we aim to recruit 96 patients undergoing elective cardiac surgery for ischaemic and/or valvular heart disease. After postoperative admission to the intensive care unit (ICU), patients will be randomly assigned to receive 5 ml/kg ideal body weight HS (7.3% NaCl) or normal saline (NS, 0.9% NaCl) infused within 60 min. Blood and urine samples will be collected preoperatively and postoperatively up to day 6 to assess changes in renal, cardiac, inflammatory, acid-base, and electrolyte parameters. Additionally, we will perform renal ultrasonography studies to assess renal blood flow before, during, and after infusion, and we will measure total body water using preoperative and postoperative body composition analysis (bioimpedance). Patients will be followed up for 90 days.DiscussionThe key objective of this study is to assess the cumulative amount of fluid administered in the intervention (HS) group versus control (NS) group during the ICU stay. In this preliminary, prospective, randomised controlled clinical trial we will test the hypothesis that use of HS results in less total fluids infused and less postoperative weight gain when compared to the standard of intensive care in cardiac surgery patients.Trial registrationClinicalTrials.gov, NCT03280745 . Registered on 12 September 2017.

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Hypertonic saline infusion suppresses apoptosis of hippocampal cells in a rat model of cardiopulmonary resuscitation.

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Hypertonic saline infusion suppresses apoptosis of hippocampal cells in a rat model of cardiopulmonary resuscitation.

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