A Sustained Rat Model for Studying the Long-Lasting Catabolic State of Sepsis

Breuillé, Denis; Voisin, Laure; Contrepois, M.; Arnal, M.; Rose, F.; Obled, Christiane

doi:10.1128/iai.67.3.1079-1085.1999

Cited by 51 publications

(29 citation statements)

References 35 publications

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“…We standardized 4 mg/kg for the subsequent treatments, since that dose reduced blood pressure and body mass 3 days after treatment, indicating cardiovascular and metabolic alterations. These complications are typical from endotoxemia, since they are triggered by disturbances of hemodynamic, substrate turnover, hormonal pattern, and protein catabolism (6).…”

Section: Discussionmentioning

confidence: 99%

Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia

Rosa

Colucci

Yokota

et al. 2016

American Journal of Physiology-Renal Physiology

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Sepsis is an uncontrolled systemic inflammatory response against an infection and a major public health issue worldwide. This condition affects several organs, and, when caused by Gram-negative bacteria, kidneys are particularly damaged. Due to the importance of renin-angiotensin system (RAS) in regulating renal function, in the present study, we aimed to investigate the effects of endotoxemia over the renal RAS. Wistar rats were injected with Escherichia coli lipopolysaccharide (LPS) (4 mg/kg), mimicking the endotoxemia induced by Gram-negative bacteria. Three days after treatment, body mass, blood pressure, and plasma nitric oxide (NO) were reduced, indicating that endotoxemia triggered cardiovascular and metabolic consequences and that hypotension was maintained by NO-independent mechanisms. Regarding the effects in renal tissue, inducible NO synthase (iNOS) was diminished, but no changes in the renal level of NO were detected. RAS was also highly affected by endotoxemia, since renin, angiotensin-converting enzyme (ACE), and ACE2 activities were altered in renal tissue. Although these enzymes were modulated, only angiotensin (ANG) II was augmented in kidneys; ANG I and ANG 1-7 levels were not influenced by LPS. Cathepsin G and chymase activities were increased in the endotoxemia group, suggesting alternative pathways for ANG II formation. Taken together, our data suggest the activation of noncanonical pathways for ANG II production and the presence of renal vasoconstriction and tissue damage in our animal model. In summary, the systemic administration of LPS affects renal RAS, what may contribute for several deleterious effects of endotoxemia over kidneys.

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Section: Discussionmentioning

confidence: 99%

Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia

Rosa

Colucci

Yokota

et al. 2016

American Journal of Physiology-Renal Physiology

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“…Through several metabolic alterations, sepsis independently promotes skeletal muscle breakdown and impairs skeletal muscle synthesis. [34][35][36] Inflammation associated with sepsis also increases oxidant burden, further leading to muscle dysfunction and dysregulation. 7,31,37,38…”

Section: Pathophysiology Of Disability Following Hospitalization For mentioning

confidence: 99%

Mobilization in severe sepsis: An integrative review

et al. 2014

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Severe sepsis is a leading cause of long-term morbidity in the United States. Up to half of severe sepsis is treated in non-intensive care unit (ICU) settings, making it applicable to hospitalist practice. Evidence has demonstrated benefits from physical therapy (PT) in myriad conditions; whether PT may benefit severe sepsis patients either within or outside the ICU is unknown. Therefore, we conduct a review of the literature to understand whether early mobilization improves outcomes in patients with severe sepsis in non-ICU settings. We summarize the pathophysiology of functional decline in severe sepsis, the efficacy of PT in other patient populations, and the potential rationale for PT interventions in patients with severe sepsis. Multiple databases were searched for keywords including length of stay, mortality, costs, mobilization and PT. Two authors (SG and VC) independently determined the eligibility of each study. A secondary review including studies of any infectious pathology with PT interventions or sepsis patients within the ICU was also conducted. Our search did not yield any primary literature regarding the impact of mobilization on severe sepsis outcomes in non-ICU settings. Only one retrospective study showed potential benefit of therapy in sepsis patients in the ICU. Similarly, in non-ICU settings, only one study that included patients with bacterial pneumonia reported outcomes after implementing an intervention consisting of early mobilization. These findings suggest that scant data regarding the efficacy of early mobilization following severe sepsis exists. Since hospitalists often care for this patient population, an opportunity for research in this area exists.

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“…After an acclimatization period of 6 days, rats were divided into four groups. Rats in groups 1 and 3 were infected with live Escherichia coli injected into a lateral tail vein (INF rats), as described previously (6). The other groups, groups 2 and 4, were injected with the same volume of saline.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis in sepsis

Ruot

Breuillé

Rambourdin

et al. 2000

American Journal of Physiology-Endocrinology and Metabolism

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Plasma albumin is well known to decrease in response to inflammation. The rate of albumin synthesis from both liver and plasma was measured in vivo by use of a large dose of L-[(2)H(3)-(14)C]valine in rats injected intravenously with live Escherichia coli and in pair-fed control rats during the acute-phase period (2 days postinfection). The plasma albumin concentration was reduced by 50% in infected rats compared with pair-fed animals. Infection induced a fall in both liver albumin mRNA levels and albumin synthesis relative to total liver protein synthesis. However, absolute liver albumin synthesis rate (ASR) was not affected by infection. In plasma, albumin fractional synthesis rate was increased by 50% in infected animals compared with pair-fed animals. The albumin ASR estimated in the plasma was similar in the two groups. These results suggest that hypoalbuminemia is not due to reduced albumin synthesis during sepsis. Moreover, liver and plasma albumin ASR were similar. Therefore, albumin synthesis measured in the plasma is a good indicator of liver albumin synthesis.

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A Sustained Rat Model for Studying the Long-Lasting Catabolic State of Sepsis

Cited by 51 publications

References 35 publications

Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia

Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia

Mobilization in severe sepsis: An integrative review

Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis in sepsis

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