Hepatic microcirculatory failure

Ramalho, Fernando Silva; Fernandez-Monteiro, Izabel; Roselló‐Catafau, Joan; Peralta, Carmen

doi:10.1590/s0102-86502006000700012

Cited by 53 publications

(49 citation statements)

References 39 publications

(46 reference statements)

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“…Hepatocellular and sinusoidal endothelial cell dysfunction occur early during hemorrhage (HEM) and persist despite adequate fluid RES (3,35,39). End-organ damage is initiated and driven by a cascade of events involving multiple mediators and pathways (i.e., proinflammatory cytokines, reactive oxygen radicals, lipoxygenase derivatives, complement, intracellular Ca 2ϩ signaling, and hypoxia).…”

Section: Discussionmentioning

confidence: 99%

Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Hurt

Matheson²,

Smith

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hurt RT, Matheson PJ, Smith JW, Zakaria ER, Shaheen SP, McClain CJ, Garrison RN. Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 303: G1144 -G1152, 2012. First published September 17, 2012 doi:10.1152/ajpgi.00278.2011.-Conventional resuscitation (CR) from hemorrhagic shock (HS) results in gut and liver hypoperfusion, organ and cellular edema, and vital organ injury. Adjunct direct peritoneal resuscitation (DPR) with dialysate prevents gut vasoconstriction, hypoperfusion, and injury. We hypothesized that DPR might also improve hepatocellular edema, inflammation, and injury. Anesthetized male SD rats were assigned to groups (n ϭ 8/group): 1) sham (no HS); 2) HS (40% MAP/60 min) ϩ intravenous fluid conventional resuscitation [CR; shed blood ϩ 2 vol saline (SAL)/30 min]; 3) HSϩCRϩDPR (30 ml ip 2.5% glucose dialysate); or 4) HSϩCRϩSAL (30 ml ip saline). Histopathology showed lung and liver injury in HSϩCR and HSϩCRϩSAL up to 24-h postresuscitation (post-RES) that was not in shams and which was prevented by adjunct DPR. Wet-to-dry weight ratios in HSϩCR revealed organ edema formation that was prevented by adjunct DPR. HSϩCR and HSϩCRϩSAL had 34% mortality by 24-h post-RES, which was absent with DPR (0%). Liver IFN-␥ and IL-6 levels were elevated in CR compared with DPR or shams. TNF-␣ mRNA was upregulated in CR/sham and DPR/sham. IL-17 was downregulated in DPR/sham. CXCL10 mRNA was upregulated in CR/sham but downregulated in DPR/sham. Despite restored central hemodynamic performance after CR of HS, liver blood flow was compromised up to 24 h post-RES, and the addition of DPR restores and maintains liver perfusion at 24-h post-RES. DPR prevented liver injury, histological damage, and edema formation compared with CR alone. DPR provided a mitigating anti-inflammatory dampening of the systemic inflammatory response. In all, these effects likely account for improved survivorship in the DPR-treated group. hemorrhagic shock; liver blood flow; liver injury DESPITE ADVANCES IN TREATMENT and therapies, hemorrhagic shock (HS) remains a major cause of morbidity and mortality following trauma in the United States (18). The clinical role the liver plays during HS and in subsequent multiple organ failure (MOF) is unclear. The largest and most recent clinical study followed 1,962 trauma patients with injury severity score Ͼ 14 (ISS Ͼ14) during a 3-year period (17). Of the patients who met the study's inclusion criteria, 154 (7.9%) exhibited signs of liver dysfunction during their hospital course. In general, these patients with liver dysfunction were older and had higher injury severity scores and lower prehospital blood pressure (17). Patients who developed high serum levels of bilirubin, a serum marker of liver injury, had longer stays in the intensive care unit and higher mortality (16.2% vs. 2.5%) compared with patients with normal or slightly elevated bilirubin. While these observational...

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Section: Discussionmentioning

confidence: 99%

Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Hurt

Matheson²,

Smith

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It has been suggested that sinusoidal perfusion alterations in steatosis lead to compression of the sinusoidal spaces and consequent disturbances of the hepatic microcirculation [21]. Accordingly, increased production or release of the vasoactive modulator nitric oxide (NO) could provide an effective novel strategy for the prevention and treatment of NAFLD [22].…”

Section: Nitric Oxidementioning

confidence: 99%

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Butterworth

Canbay

2018

Dig Dis

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Background: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited. Summary: L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with non-alcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties. Key Messages: (1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.

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“…For instance, various degrees of thrombocytopenia are commonly observed after liver transplantation, especially during the first postoperative week, and some clinical studies have demonstrated that thrombocytopenia was significantly associated with poor prognosis [69]. The imbalance between endothelin and nitric oxide produced by the SEC may lead to active vasoconstriction, narrowing of the sinusoidal lumen, and subsequent sinusoidal microcirculatory disturbance [70]. During the past decade, the measurement of plasma ADAMTS13:AC was utilized as a differential diagnostic tool for TMAs [68], but its relevance to organ transplantation itself was not well evaluated.…”

Section: Liver Transplantationmentioning

confidence: 99%

Pivotal role of ADAMTS13 function in liver diseases

Uemura

Fujimura

et al. 2010

Int J Hematol

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The liver is a major source of clotting and fibrinolytic proteins, and plays a central role in thrombo-regulation. Patients with advanced liver diseases tend to bleed because of reduced plasma levels of several clotting factors and thrombocytopenia, but they do also exhibit thrombotic complications. ADAMTS13 is a metalloproteinase, produced exclusively in hepatic stellate cells, and specifically cleaves highly multimeric von Willebrand factor (VWF). VWF plays a pivotal role in hemostasis and thrombosis, and its function is dependent on its multimeric state. Deficiency of ADAMTS13 results in accumulation of unusually large VWF multimers (UL-VWFM) in plasma, in turn induces platelet clumping or thrombi under high shear stress, followed by microcirculatory disturbances. Considering that UL-VWFM, the substrate of ADAMTS13, is produced in transformed vascular endothelial cells at sites of liver injury, decreased ADAMTS13 activity may be involved in not only sinusoidal microcirculatory disturbances, but also subsequent progression of liver injuries, eventually leading to multiorgan failure. This concept can be applied to the development or aggravation of liver diseases, including liver cirrhosis, alcoholic hepatitis, veno-occlusive disease, and adverse events after liver transplantation. These results promise to bring further understanding of the pathophysiology of liver diseases, and offer new insight for development of therapeutic strategies.

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Hepatic microcirculatory failure

Cited by 53 publications

References 39 publications

Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Pivotal role of ADAMTS13 function in liver diseases

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