Hemorrhage Activates Myocardial NFκB and Increases TNF-α in the Heart

Meldrum, Daniel R.; Shenkar, Robert; Sheridan, Brett C.; Cain, Brian S.; Abraham, Edward; Harken, Alden H.

doi:10.1006/jmcc.1997.0506

Cited by 135 publications

(77 citation statements)

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“…Simultaneous with improvement in cardiac function, RSV treatment resulted in decreased systemic TNF-α level and elevated cardiac ATP content (Figures 3 and 5). An exacerbated proinflammatory response following T-H is well documented (39)(40)(41). Our experiments clearly show improved cardiac function in RSV recipients, although the salutary effect of RSV is likely due to its effect on multiple organs and systemic inflammatory pathways.…”

Section: Discussionsupporting

confidence: 60%

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

Jian

Yang

Chaudry

et al. 2011

Mol Med

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Mitochondria play a critical role in metabolic homeostasis of a cell. Our recent studies, based on the reported interrelationship between c-Myc and Sirt1 (mammalian orthologue of yeast sir2 [silent information regulator 2]) expression and their role in mitochondrial biogenesis and function, demonstrated a significant downregulation of Sirt1 protein expression and an upregulation of c-Myc following trauma-hemorrhage (T-H). Activators of Sirt1 are known to improve mitochondrial function and the naturally occurring polyphenol resveratrol (RSV) has been shown to significantly increase Sirt1 activity by increasing its affinity to both NAD+ and the acetylated substrate. In this study we tested the salutary effect of RSV following T-H and its influence on Sirt1 expression. Rats were subjected to T-H or sham operation. RSV (8 mg/kg body weight, intravenously) or vehicle was administered 10 min after the onset of resuscitation, and the rats were killed 2 h following resuscitation. Sirtinol, a Sirt1 inhibitor, was administered 5 min prior to RSV administration. Cardiac contractility (±dP/dt) was measured and heart tissue was tested for Sirt1, Pgc-1α, c-Myc, cytosolic cytochrome C expression and ATP level. Left ventricular function, after T-H, was improved (P < 0.05) following RSV treatment, with significantly elevated expression of Sirt1 (P < 0.05) and Pgc-1α (P < 0.05), and decreased c-Myc (P < 0.05). We also observed significantly higher cardiac ATP content, declined cytosolic cytochrome C and decreased plasma tumor necrosis factor-α in the T-H-RSV group. The salutary effect due to RSV was abolished by sirtinol, indicating a Sirt1-mediated effect. We conclude that RSV may be a useful adjunct to resuscitation fluid following T-H.

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Section: Discussionsupporting

confidence: 60%

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

Jian

Yang

Chaudry

et al. 2011

Mol Med

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“…[40][41][42] Numerous studies have shown that leukocytes are activated early during HS and are responsible for cytokine production and tissue injury. 43,44 Moreover, in rats, bacterial translocation has also been involved in the development of organ failure. 45 Indeed, several attempts in down-modulating HS-associated inflammation by using various compounds have been promising, supporting the inflammatory hypothesis of HS-induced organ failure.…”

Section: Trem-1 Structure and Functionmentioning

confidence: 99%

Triggering receptor expressed on myeloid cells -1 as a new therapeutic target during inflammatory diseases

Derive¹,

Massin

Gibot³

2010

Self/Nonself

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“…Many studies have demonstrated that trauma-hemorrhage induces marked alterations in various immune functions (Meldrum et al, 1997;Murphy et al, 2005;Murphy et al, 2004;Noel et al, 2005;Shukla et al, 2004;Zuckerbraun et al, 2005). Severe hemorrhage followed by adequate resuscitation with blood and crystalloid solutions is known to produce depression of immune system, such as lymphocyte functions and macrophage functions (Chaudry and Ayala, 1993).…”

Section: Introductionmentioning

confidence: 99%

17β-Estradiol's salutary effects on splenic dendritic cell functions following trauma–hemorrhage are mediated via estrogen receptor-α

Kawasaki

Choudhry

Suzuki

et al. 2008

Molecular Immunology

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Although 17β-estradiol administration following trauma-hemorrhage attenuates Kupffer cell, splenic and peritoneal macrophage functions, it remains unknown whether 17β-estradiol has any salutary effects on splenic dendritic cell (DC) functions and if so, whether such effects are mediated via the estrogen receptors (ER). We hypothesized that 17β-estradiol administration following traumahemorrhage has salutary effects on splenic DC functions. Male C3H/HeN (6-8 weeks) mice were randomly assigned to sham operation or trauma-hemorrhage. Trauma-hemorrhage was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure [BP] 35 mmHg), followed by fluid resuscitation (4 × the shed blood volume in the form of Ringer's lactate). Estrogen receptor (ER)-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropionitrile (DPN; 5μg/ kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Two hrs later, the mice were sacrificed, splenic DCs were isolated and the changes in their apoptosis, co-stimulating factors and MHC class II expression, ability to produce cytokines, and antigen presentation capacity were measured. Apoptosis of splenic DC increased following trauma-hemorrhage; however, 17β-estradiol administration after trauma-hemorrhage normalized the rate of apoptosis. Moreover, splenic DC cytokines production, co-stimulating factors and MHC class II expression, and antigen presentation capacity were significantly decreased following traumahemorrhage; however, 17β-estradiol as well as PPT also prevented these depressions. In contrast, DPN did not attenuate splenic DC functions following trauma-hemorrhage. Since PPT administration following trauma-hemorrhage was more effective in normalizing splenic DC functions than DPN, the salutary effects of 17β-estradiol on splenic DC functions are mediated predominantly via ER-α.

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Hemorrhage Activates Myocardial NFκB and Increases TNF-α in the Heart

Cited by 135 publications

References 0 publications

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

Triggering receptor expressed on myeloid cells -1 as a new therapeutic target during inflammatory diseases

17β-Estradiol's salutary effects on splenic dendritic cell functions following trauma–hemorrhage are mediated via estrogen receptor-α

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