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Introduction: The mechanisms underlying the protective effects of atrial natriuretic peptide (ANP) on the gut barrier during traumatic hemorrhagic shock (THS) remain elusive. This study aimed to explore the potential role of ANP in safeguarding against gut barrier dysfunction after THS, focusing on the PLC-γ1/ROS feedback loop. Methods: In our THS rat model, we randomly allocated male Sprague-Dawley rats to receive intravenous ANP with or without a concurrent NADPH oxidase/p38 MAPK inhibitor during the shock phase. After 24 h, we assessed circulatory and jejunal ANP, ROS, intestinal tight junction proteins, and apoptosis to evaluate the effects of ANP on the gut barrier and its interplay with intestinal ANP and ROS. Rat small intestinal epithelial cells (IECs) were also treated with ANP and subjected to hypoxia/re-oxygenation injury, with or without PI3K/PLC inhibition, to elucidate the relationship between ANP/ROS signaling and PLC-γ1. Furthermore, we modulated PLC-γ1 expression in these IECs to examine its impact on ROS and ANP production. Results: Intravenous ANP administration at 0.025 μg/kg/min during THS significantly increased intestinal ANP and ROS levels at 24 h. ANP treatment enhanced the expression of intestinal tight junction proteins and reduced IEC apoptosis. Inhibition of circulatory ROS diminished intestinal ANP levels, while suppression of circulatory ANP led to a reduction in intestinal ROS. Decreasing PLC-γ1 expression in hypoxia/re-oxygenation-treated IECs resulted in lower ROS and ANP levels, whereas augmenting PLC-γ1 expression did not alter these levels. Additionally, PI3K inhibition markedly decreased PLC-γ1 expression in these cells. Conclusion: ANP-induced protection of the intestinal barrier in THS is mediated by an intrinsic PLC-γ1/ROS positive feedback loop. ANP preserves gut barrier integrity and reduces IEC apoptosis through this mechanism. Further studies are warranted to investigate the interaction between IECs and other cellular components within the PLC-γ1/ROS loop. [ABSTRACT FROM AUTHOR]

Introduction:Among major trauma patients in the emergency department, the leading cause of morbidity and mortality is a hemorrhagic shock. The low oxygen flow with hypovolemia in trauma patients is believed to play a significant role. Hence, oxygen supply is essential in severe trauma patients with massive hemorrhage. This study aimed to investigate the effect of oxygen supply in hypoxic condition and variable treatments such as pentoxifylline (PTX), glycerol, hypertonic saline (HTS), protease inhibitor, and dexamethasone (DEXA) in macrophage and T cells. Method:Nitric oxide synthase (iNOS) and macrophage migration inhibitory factor (MIF) were measured for macrophage. MIF, interleukin (IL)-2, and IL-8 were measured for T cells. T cell viability was measued by MTT assay. Results: Pentoxifylline decreased iNOS expression mostly followed by glycerol under hypoxia. Under the hyperoxia, PTX and other treatments decreased iNOS expressions in macrophage. MIF expression was lowered with PTX under hypoxia. PTX, glycerol, HTS, and protease inhibitor were effective under hyperoxia in macrophage. PTX increased T cell survival under hypoxia. Under the hyperoxia, IL-2 expressions were upregulated with PTX, glycerol, and HTS. PTX and other treatments were effective for IL-8. Our results indicate that the PTX and the other agents tested reversed the effects of stimulation of lipopolysaccharide, PGE2 in hypoxia or hypoxia. Conclusion:Our study demonstrated potential usefulness in improving immune systems during severe inflammatory conditions similar to septic shock possibly caused by massive hemorrhage. [ABSTRACT FROM AUTHOR]

Introduction:Among major trauma patients in the emergency department, the leading cause of morbidity and mortality is a hemorrhagic shock. The low oxygen flow with hypovolemia in trauma patients is believed to play a significant role. Hence, oxygen supply is essential in severe trauma patients with massive hemorrhage. This study aimed to investigate the effect of oxygen supply in hypoxic condition and variable treatments such as pentoxifylline (PTX), glycerol, hypertonic saline (HTS), protease inhibitor, and dexamethasone (DEXA) in macrophage and T cells. Method:Nitric oxide synthase (iNOS) and macrophage migration inhibitory factor (MIF) were measured for macrophage. MIF, interleukin (IL)-2, and IL-8 were measured for T cells. T cell viability was measued by MTT assay. Results: Pentoxifylline decreased iNOS expression mostly followed by glycerol under hypoxia. Under the hyperoxia, PTX and other treatments decreased iNOS expressions in macrophage. MIF expression was lowered with PTX under hypoxia. PTX, glycerol, HTS, and protease inhibitor were effective under hyperoxia in macrophage. PTX increased T cell survival under hypoxia. Under the hyperoxia, IL-2 expressions were upregulated with PTX, glycerol, and HTS. PTX and other treatments were effective for IL-8. Our results indicate that the PTX and the other agents tested reversed the effects of stimulation of lipopolysaccharide, PGE2 in hypoxia or hypoxia. Conclusion:Our study demonstrated potential usefulness in improving immune systems during severe inflammatory conditions similar to septic shock possibly caused by massive hemorrhage. [ABSTRACT FROM AUTHOR]

The biological effect of atrial natriuretic peptide (ANP) in traumatic hemorrhagic shock (THS) is unknown. This study was to evaluate whether ANP therapy can show organ protection in THS. Thirty male Sprague-Dawley rats were divided into three groups: ANP group, sham group, and control group. Pressure-controlled THS was induced in rats in ANP group and control group. ANP at a rate of 0.025 μg/kg/min was infused in ANP group during near-80 min of shock. After that, animals were resuscitated for 60 min and observed until 24 h. Hemodynamic parameters during shock and resuscitation were measured. Serum levels of ANP and lactate dehydrogenase, tissue oxidative stress and inflammatory factors, as well as liver and kidney function were determined. Tissue apoptosis was also assessed. There was no statistically significant difference between ANP group and control group in arterial pressure throughout the 150 min monitoring period. Blood urea nitrogen at 90 min and 24 h in ANP group was significantly lower than control group. Alanine transaminase and aspartate aminotransferase activity at 90 min in control group were significantly higher than that in sham group. However, hepatic enzyme activity at 90 min in ANP group was not significantly different compared with sham or control group. After 24 h, myocardial expression of caspase 3 protein in ANP group was significantly reduced compared with control group. Jejunal and hepatic Malondialdehyde was increased following ANP treatment. ANP therapy during early THS has no significant adverse effect on hemodynamics but can exert oxidative stress and certain protective effect on multiple organs. Our study may shed light on the novel therapy of THS with regard to organ protection. The mechanisms underlying the organ protection require further study. [ABSTRACT FROM AUTHOR]

The biological effect of atrial natriuretic peptide (ANP) in traumatic hemorrhagic shock (THS) is unknown. This study was to evaluate whether ANP therapy can show organ protection in THS. Thirty male Sprague-Dawley rats were divided into three groups: ANP group, sham group, and control group. Pressure-controlled THS was induced in rats in ANP group and control group. ANP at a rate of 0.025 μg/kg/min was infused in ANP group during near-80 min of shock. After that, animals were resuscitated for 60 min and observed until 24 h. Hemodynamic parameters during shock and resuscitation were measured. Serum levels of ANP and lactate dehydrogenase, tissue oxidative stress and inflammatory factors, as well as liver and kidney function were determined. Tissue apoptosis was also assessed. There was no statistically significant difference between ANP group and control group in arterial pressure throughout the 150 min monitoring period. Blood urea nitrogen at 90 min and 24 h in ANP group was significantly lower than control group. Alanine transaminase and aspartate aminotransferase activity at 90 min in control group were significantly higher than that in sham group. However, hepatic enzyme activity at 90 min in ANP group was not significantly different compared with sham or control group. After 24 h, myocardial expression of caspase 3 protein in ANP group was significantly reduced compared with control group. Jejunal and hepatic Malondialdehyde was increased following ANP treatment. ANP therapy during early THS has no significant adverse effect on hemodynamics but can exert oxidative stress and certain protective effect on multiple organs. Our study may shed light on the novel therapy of THS with regard to organ protection. The mechanisms underlying the organ protection require further study. [ABSTRACT FROM AUTHOR]

Ideal concentrations of inhaled oxygen with regard to lung protection during early traumatic hemorrhagic shock (THS) remain unknown especially in the era of targeted temperature management (TTM). We speculated that a significant increase in oxygen supply in early stage of THS would magnify the protecting role of hypothermia in acute lung injury. Forty male New Zealand rabbits were randomly divided into four groups (n = 10): sham group, control group, group 1, and group 2. Except for sham group, all other animals were submitted to 30 min of uncontrolled THS and received limited fluid resuscitation for 60 min. During resuscitation, in addition to 34°C of TTM, animals in group 1 inhaled 21% oxygen while animals in group 2 inhaled 50% oxygen. Animals in control group inhaled room air and were kept normothermia. Oxidative stress, inflammation, and apoptosis parameters in the lung tissues were determined. THS induced higher expression of malondialdehyde, surfactant protein A, nuclear factor kappa B, and caspase 3 as well as lower expression of Bcl-2 mRNA and superoxide dismutase activity. Compared with inhalation of 21% oxygen, inhalation of 50% oxygen during TTM significantly improves oxidative stress, inflammation, apoptosis, and acute lung injury. Oxygen supplement during TTM therapy alleviated acute lung injury in the early stage of THS. Further studies are required to explore the ideal combination forms of TTM and oxygen supplement with the purpose of maximizing therapeutic effect while minimizing adverse effects. [ABSTRACT FROM AUTHOR]

Ideal concentrations of inhaled oxygen with regard to lung protection during early traumatic hemorrhagic shock (THS) remain unknown especially in the era of targeted temperature management (TTM). We speculated that a significant increase in oxygen supply in early stage of THS would magnify the protecting role of hypothermia in acute lung injury. Forty male New Zealand rabbits were randomly divided into four groups (n = 10): sham group, control group, group 1, and group 2. Except for sham group, all other animals were submitted to 30 min of uncontrolled THS and received limited fluid resuscitation for 60 min. During resuscitation, in addition to 34°C of TTM, animals in group 1 inhaled 21% oxygen while animals in group 2 inhaled 50% oxygen. Animals in control group inhaled room air and were kept normothermia. Oxidative stress, inflammation, and apoptosis parameters in the lung tissues were determined. THS induced higher expression of malondialdehyde, surfactant protein A, nuclear factor kappa B, and caspase 3 as well as lower expression of Bcl-2 mRNA and superoxide dismutase activity. Compared with inhalation of 21% oxygen, inhalation of 50% oxygen during TTM significantly improves oxidative stress, inflammation, apoptosis, and acute lung injury. Oxygen supplement during TTM therapy alleviated acute lung injury in the early stage of THS. Further studies are required to explore the ideal combination forms of TTM and oxygen supplement with the purpose of maximizing therapeutic effect while minimizing adverse effects. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock (HS) induces a compensatory endocrine and cytokine response which aims to restore homeostasis. This response can be modulated by general anesthetics. To our knowledge, no studies have evaluated if etomidate modulates this response in experimental HS. After being premedicated with buprenorphine (0.05 mg/kg subcutaneously), male Wistar rats were anaesthetized with 5% isoflurane and divided into three groups: G1 (control, n = 16), G2 (n = 13), and G3 (n = 14). G2 and G3 were subjected to HS by collecting 30% of their blood volume and resuscitated 90 min later with the collected blood and normal saline, in a 1:3 ratio, respectively. G3 received etomidate (1 mg/kg IV) before HS. Blood gas analysis, adrenocorticotropic hormone (ACTH), corticosterone, and plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and of TNF-α, IL-6, and IL-10 mRNA obtained through real-time polymerase chain reaction (RT-PCR) were measured at 0, 90, 150, and 240 min after HS induction. Compared with G2, etomidate-treated animals had significantly lower corticosterone, PO2, PO2/FiO2, base excess and HCO3, and higher TNF-α, IL-6, IL-10, and TNF-α mRNA levels (P <0.05). Etomidate-treated rats showed impaired adrenal and increased cytokine response to HS and evidence of worse tissue oxygenation and lung dysfunction. Based on these results, and until further studies are performed to confirm if these findings occur in clinical patients, we suggest that etomidate should be used cautiously in HS. [ABSTRACT FROM AUTHOR]