Induced Hypothermia Attenuates the Acute Lung Injury in Hemorrhagic Shock

Kim, Kyuseok; Kim, Woojeong; Rhee, Joong Eui; Jo, You Hwan; Lee, Jae Hyuk; Kim, Kyung Soo; Kwon, Woon Yong; Suh, Gil Joon; Lee, Christopher C.; Singer, Adam J.

doi:10.1097/ta.0b013e3181a73eea

Cited by 36 publications

(24 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our experiments confirmed that AIH was able to significantly inhibit the NF-κB pathway. This result was consistent with other studies [10,35,36]. In LPS-stimulated inflammatory pathways, JNK signaling is key for cytokine production [37].…”

Section: Discussionsupporting

confidence: 94%

Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Wang

Zhang

et al. 2014

International Immunopharmacology

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 94%

Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Wang

Zhang

et al. 2014

International Immunopharmacology

View full text Add to dashboard Cite

“…The method for objective quantification of the injury has been described previously (14). In brief, ALI was classified into four categories based on the severity of alveolar congestion and hemorrhage, infiltration of neutrophils in the air spaces or vessel walls, and the thickness of alveolar wall.…”

Section: Methodsmentioning

confidence: 99%

Creating a Prosurvival Phenotype Through a Histone Deacetylase Inhibitor in a Lethal Two-Hit Model

Liu¹,

Li²,

Wang³

et al. 2014

Shock

View full text Add to dashboard Cite

Objectives Hemorrhagic shock (HS) can initiate an exaggerated systemic inflammatory response and multiple organ failure, especially if followed by a subsequent inflammatory insult (“second hit”). We have recently shown that histone deacetylase inhibitors can improve survival in rodent models of HS or septic shock, individually. In the present study, we examined whether valproic acid (VPA), a histone deacetylase inhibitor, could prolong survival in a rodent “two-hit” model: HS followed by septic shock from cecal ligation and puncture (CLP). Methods Male Sprague-Dawley rats (250–300 g) were subjected to sublethal HS (40% blood loss) and then randomly divided into two groups (n = 7/group): VPA and control. The VPA group was treated intraperitoneally with VPA (300 mg/kg in normal saline [NS], volume = 750 μL/kg). The control group was injected with 750 μL/kg NS. After 24 h, all rats received CLP followed immediately by injection of the same dose of VPA (VPA group) or NS (vehicle group). Survival was monitored for 10 days. In a parallel study, serum and peritoneal irrigation fluid from VPA- or vehicle-treated rats were collected 3, 6, and 24 h after CLP, and enzyme-linked immunosorbent assay was performed to analyze myeloperoxidase activity and determine tumor necrosis factor α and interleukin 6 concentrations. Hematoxylin-eosin staining of lungs at 24-h time point was performed to investigate the grade of acute lung injury. Results Rats treated with VPA (300 mg/kg) showed significantly higher survival rates (85.7%) compared with the control (14.3%). Moreover, VPA significantly suppressed myeloperoxidase activity (marker of neutrophil-mediated oxidative damage) and inhibited levels of proinflammatory cytokine tumor necrosis factor α and interleukin 6 in the serum and peritoneal cavity. Meanwhile, the severity of acute lung injury was significantly reduced in VPA-treated animals. Conclusions We have demonstrated that VPA treatment improves survival and attenuates inflammation in a rodent two-hit model.

show abstract

“…The method for objective quantification of the injury has been described previously. 23 In each animal, three separate lung sections were graded to generate the mean score.…”

Section: Methodsmentioning

confidence: 99%

Synergistic effects of hypertonic saline and valproic acid in a lethal rat two-hit model

Liu

et al. 2013

Journal of Trauma and Acute Care Surgery

View full text Add to dashboard Cite

BACKGROUND Hemorrhagic shock (HS) followed by an infection (“second hit”) can lead to severe systemic inflammatory response and multiple-organ failure. Studies have shown that resuscitation with hypertonic saline (HTS) can blunt the inflammatory response. We demonstrated that large doses of valproic acid (VPA, 300 mg/kg), a histone deacetylase inhibitor, improves survival in a rodent two-hit model (HS followed by cecal ligation and puncture [CLP]). In the present study, we examined whether combination of HTS with VPA would allow us to achieve survival advantage at a lower dose of VPA (200 mg/kg). METHODS Male Sprague-Dawley rats were subjected to HS (50% blood loss) and randomized into five groups (n = 7–8 per group) as follows: (1) isotonic sodium chloride solution (ISCS), (2) 7.5% saline, (3) VPA, (4) ISCS + VPA, and (5) HTS + VPA. After 24 hours, they underwent CLP, followed by the same doses of ISCS, HTS, and/or VPA and were monitored for 10 days. In a parallel experiment, blood, peritoneal irrigation fluid and lung homogenate were subjected to enzyme-linked immunosorbent assay 3 hours and 24 hours after CLP to measure myeloperoxidase activity and proinflammatory cytokines tumor necrosis factor α and interleukin 1β levels. Western blotting was performed to investigate the expression of pentraxin 3 protein in the lung homogenate at 24 hours after CLP. Hematoxylin and eosin staining of lungs at the 24 hours were performed to quantify the degree of acute lung injury. RESULTS HTS + VPA treatment significantly improved survival (87.5%), compared with the other groups (14.3%; p < 0.05), while attenuating peritoneal myeloperoxidase levels and proinflammatory cytokine tumor necrosis factor α and interleukin 1β levels in the serum, peritoneal cavity, and lung. The degree of acute lung injury and expression of pentraxin 3 in the lung were significantly reduced in the HTS + VPA group. CONCLUSION This is the first study to show that VPA and HTS can work synergistically to attenuate inflammation and improve survival in a lethal two-hit model.

show abstract

Induced Hypothermia Attenuates the Acute Lung Injury in Hemorrhagic Shock

Abstract: HT attenuates HS-induced ALI in rats by the modulation of GSK, HSP 72, iNOS, and NF-kappaB.

Cited by 36 publications

References 59 publications

Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Creating a Prosurvival Phenotype Through a Histone Deacetylase Inhibitor in a Lethal Two-Hit Model

Synergistic effects of hypertonic saline and valproic acid in a lethal rat two-hit model

Contact Info

Product

Resources

About