Sepsis

Chaudry, Irshad H.

doi:10.1001/archsurg.134.9.922

Cited by 43 publications

(2 citation statements)

References 83 publications

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“…No less important for modeling/translational purposes are variations within populations of human patients themselves. Trauma/sepsis patients typically receive allogeneic blood transfusion ( versus shed blood in animals), different doses of morphine-based products ( versus lack of and/or set doses of non-/morphine substances), inotropic agents and others, a majority of which produce strong immune-inflammatory effects that are very difficult to account for and match experimentally (93). Thus, patient studies are fraught with numerous small and large differences in the manner in which clinical care and standard procedures are carried out at different institutions.…”

Section: The Good and The Bad: The Role Of Mouse Models In Critical Imentioning

confidence: 99%

Abandon the Mouse Research Ship? Not Just Yet!

Osuchowski¹,

Remick

Lederer

et al. 2014

Shock

Self Cite

128

123

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Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiological alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly-publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without over-interpretation. Hopefully a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

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Section: The Good and The Bad: The Role Of Mouse Models In Critical Imentioning

confidence: 99%

Abandon the Mouse Research Ship? Not Just Yet!

Osuchowski¹,

Remick

Lederer

et al. 2014

Shock

Self Cite

128

123

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show abstract

“…Septic shock remains the most common cause of death in intensive care units despite extensive research into both the basic mechanisms and clinical aspects of this syndrome [5,9,27]. Although the pathogenic sequence of events in septic shock has been extensively examined [for reviews, see refs.…”

Section: Introductionmentioning

confidence: 99%

Sepsis Correlated with Increased Erythrocyte Na+ Content and Na+-K+ Pump Activity

Hsieh¹,

Hwang²,

Chen³

et al. 2003

J Biomed Sci

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The aims of the present study were twofold: (1) simultaneous determinations of Na⁺ transport parameters of erythrocytes from 40 healthy donors and 28 septic patients as assessed by a score of severity of sepsis (SSS), and (2) examination of the correlation between the SSS and specific Na⁺ transport abnormalities. Erythrocytes were obtained and loaded with different ionic compositions and cellular Na⁺ contents before determination of the near-maximal Na⁺ pump rate (Vmax), the physiological extrusion rate of Na⁺ (v) and the number of ouabain-binding sites (Bmax). In erythrocytes from septic patients, the cellular Na⁺ content was 28% higher (p < 0.001), with no differences in water content compared to erythrocytes from healthy donors. This elevated Na⁺ content was accompanied by significantly higher values for Vmax (43%), v (24%) and Bmax (48%) of the Na⁺ pump in septic erythrocytes. Moreover, significant positive correlations existed between Vmax and SSS (p = 0.028) and between cellular Na⁺ content and SSS (p = 0.005). These data suggest that during sepsis, membrane alterations occur and result in an increased cellular Na⁺ content. Active Na⁺ transport (Vmax and v) was significantly stimulated, possibly as a consequence of a secondary response to the elevated Na⁺ of cells. Both cellular Na⁺ and Vmax correlated well with the severity of sepsis, suggesting that these altered transport parameters may reflect the progress of sepsis.