May 1, 2005Critical Care Medicine

Tumor necrosis factor-α-induced caspase activation mediates endotoxin-related cardiac dysfunction*

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Why the study?

Does caspase inhibition prevent lipopolysaccharide-induced cardiac dysfunction in mice?

Population

Adult male wild-type and TNF receptor 1/receptor 2 knockout mice

Comparison

Intraperitoneal lipopolysaccharide with or… vs Wild-type vs TNFR-1/2 knockout mice; zVAD vs no…

Design

Preclinical

Follow-up

24 hours

Authors

DCDeborah CarlsonSouthwestern Medical Center MWMonte S. WillisHeart Failure & Transplant DWD. Jean WhiteUniversity of Cambridge

Discussion

Member takes

Implication

Caspase inhibition may attenuate endotoxin-mediated cardiac dysfunction in mice; hypothesis-generating for human septic cardiomyopathy.

Structured PICO

Does caspase inhibition prevent lipopolysaccharide-induced cardiac dysfunction in mice?

Population

Adult male wild-type (B6:129PF1/J) and TNF receptor 1/receptor 2 (TNFR-1/2) knockout mice (B6;129S-Tnfrsf1aTnfrsf1b)

Intervention

Intraperitoneal lipopolysaccharide (4 mg/kg) with or without broad-spectrum caspase inhibitor Z-Val-Ala-Asp (ome)-FMK (zVAD)

Comparator

Wild-type vs TNFR-1/2 knockout mice; zVAD vs no zVAD

Outcome

Cardiac apoptosis (measured by caspase-3 and -8 activity, Bax/Bcl-2 levels, TUNEL staining) and cardiac physiologic function (isolated beating hearts/Langendorff preparation) at 2, 4, 8, and 24 hrssurrogate

Endotoxin induces a TNF-alpha-dependent apoptotic cascade in the myocardium that contributes to cardiac dysfunction, which can be mitigated by caspase inhibition.

Cite This Study

Carlson et al. (2005) studied this question.

synapsesocial.com/papers/6a890202185d41e08f75fdb9 https://doi.org/10.1097/01.ccm.0000163398.79679.66

Topics

Bremelanotide

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Tumor necrosis factor-α-induced caspase activation mediates endotoxin-related cardiac dysfunction*

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Topics

Tumor necrosis factor-α-induced caspase activation mediates endotoxin-related cardiac dysfunction*

Discussion

Member takes

Implication

Structured PICO

Cite This Study

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Topics

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