Gut and Liver

Smaïl, Nadia; Catania, Robert A.; Wang, Ping; Cioffi, William G.; Bland, Kirby I.; Chaudry, Irshad H.

doi:10.1001/archsurg.133.4.399

Cited by 35 publications

(2 citation statements)

References 35 publications

(41 reference statements)

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“…This well-described iNOS induction following trauma has been shown in the liver [8, 31], lung [6], spleen [11], gut [32], thymus and vascular system [7]. Here we confirm that iNOS mRNA and protein are upregulated early in the spleen.…”

Section: Discussionsupporting

confidence: 86%

Inducible Nitric Oxide Synthase Contributes to Immune Dysfunction Following Trauma

Darwiche¹,

Pfeifer²,

Menzel³

et al. 2012

Shock

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Trauma results in a persistent depression in adaptive immunity which contributes to patient morbidity and mortality. This state of immune paralysis following trauma is characterized by a change in cell-mediated immunity, specifically a depression in T-cell function and a shift towards Th2 T-cell phenotype. Upregulation of iNOS is well-recognized after injury and contributes to the inflammatory response and organ damage early after trauma. However, it is unknown whether iNOS plays a role in adaptive immune dysfunction after trauma. This study utilized a murine model of severe peripheral tissue injury to show that iNOS is rapidly upregulated in macrophages and a (Gr-1hi-CD11bhi) MDSC subpopulation in the spleen. Through the use of iNOS knockout mice, a specific iNOS inhibitor and an NO scavenger this study demostrates that iNOS-derived NO is required for the depression in T lymphocyte proliferation, interferon-gamma and interleukin-2 production within the spleen at 48hr after trauma. These findings support the hypothesis that iNOS regulates immune suppression following trauma, and suggest that targeting the sustained production of NO by iNOS may attenuate post-traumatic immune depression.

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Section: Discussionsupporting

confidence: 86%

Inducible Nitric Oxide Synthase Contributes to Immune Dysfunction Following Trauma

Darwiche¹,

Pfeifer²,

Menzel³

et al. 2012

Shock

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“…The reperfusion phase of haemorrhagic shock is associated with an inflammatory response, including increased NF-κB activation [1], increased inflammatory cytokine production [2], increased nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression [3,4], and increased activation of vascular K + ATP channels. These inflammatory responses are associated with hypotension, vasodilation and hyporesponsiveness to vasopressor agents and lead to ischaemia-reperfusion (I/R) organ injury [5].…”

Section: Introductionmentioning

confidence: 99%

Compared effects of inhibition and exogenous administration of hydrogen sulphide in ischaemia-reperfusion injury

et al. 2013

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IntroductionHaemorrhagic shock is associated with an inflammatory response consecutive to ischaemia-reperfusion (I/R) that leads to cardiovascular failure and organ injury. The role of and the timing of administration of hydrogen sulphide (H2S) remain uncertain. Vascular effects of H2S are mainly mediated through K+ATP-channel activation. Herein, we compared the effects of D,L-propargylglycine (PAG), an inhibitor of H2S production, as well as sodium hydrosulphide (NaHS), an H2S donor, on haemodynamics, vascular reactivity and cellular pathways in a rat model of I/R. We also compared the haemodynamic effects of NaHS administered before and 10 minutes after reperfusion.MethodsMechanically ventilated and instrumented rats were bled during 60 minutes in order to maintain mean arterial pressure at 40 ± 2 mmHg. Ten minutes prior to retransfusion, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl) or PAG (50 mg/kg). PNU, a pore-forming receptor inhibitor of K+ATP channels, was used to assess the role of K+ATP channels.ResultsShock and I/R induced a decrease in mean arterial pressure, lactic acidosis and ex vivo vascular hyporeactivity, which were attenuated by NaHS administered before reperfusion and PNU but not by PAG and NaHS administered 10 minutes after reperfusion. NaHS also prevented aortic inducible nitric oxide synthase expression and nitric oxide production while increasing Akt and endothelial nitric oxide synthase phosphorylation. NaHS reduced JNK activity and p-P38/P38 activation, suggesting a decrease in endothelial cell activation without variation in ERK phosphorylation. PNU + NaHS increased mean arterial pressure when compared with NaHS or PNU alone, suggesting a dual effect of NaHS on vascular reactivity.ConclusionNaHS when given before reperfusion protects against the effects of haemorrhage-induced I/R by acting primarily through a decrease in both proinflammatory cytokines and inducible nitric oxide synthase expression and an upregulation of the Akt/endothelial nitric oxide synthase pathway.Keywords: hydrogen sulphide, inflammation mediators, therapeutic use, shock, hemorrhagic/drug therapy, haemodynamics/drug effects

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Intravital intestinal videomicroscopy: Techniques and experiences

Matheson

2005

Microsurgery

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Intravital videomicroscopy (IVM) of the gastrointestinal (GI) tract is a sophisticated and powerful technique to directly observe the neurologically intact microvasculature of rats in naive and pathological conditions. We combine IVM with other techniques (i.e., vascular ring tension analysis and colorimetric microsphere determination of whole organ blood flow) to develop a strategy for the systematic analysis of the regulation of GI blood flow in healthy animals and in models of systemic sepsis and resuscitated hemorrhagic shock. We also study the molecular biology of the GI tract (enzyme- or radio-linked immunosorbent assays, fluorescent Greiss assay, and immunoblots) to correlate expression and levels of vascular mediators in tissue and arterial, venous, and portal blood with functional activity of the GI microvascular tree. When combined, these techniques develop a picture of gut pathophysiology at the level of the endothelium, vascular smooth muscle cells, and blood cells in the microcirculation. Our work led us to the general hypothesis that altered microcirculatory function in disease states lies primarily at the level of the interface between vascular and tissue physiology, i.e., the endothelial cell. This review focuses on methods and techniques for studying microvascular function, and concludes with focused reviews of pertinent findings.

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Gut and Liver

Cited by 35 publications

References 35 publications

Inducible Nitric Oxide Synthase Contributes to Immune Dysfunction Following Trauma

Inducible Nitric Oxide Synthase Contributes to Immune Dysfunction Following Trauma

Compared effects of inhibition and exogenous administration of hydrogen sulphide in ischaemia-reperfusion injury

Intravital intestinal videomicroscopy: Techniques and experiences

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