Intraperitoneal adipose tissue is strongly related to survival rate in a mouse cecal ligation and puncture model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

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PENGARUH CHLOROQUINE TERHADAP INTERLEUKIN-1β, AKTIVASI CASPASE-1 DAN SURVIVAL RATE PADA TIKUS MODEL SEPSIS

Biomedika ◽

10.23917/biomedika.v9i1.4347 ◽

2017 ◽

Vol 9 (1) ◽

Author(s):

Aryo Suseno ◽

Tatar Sumandjar ◽

HM Bambang Purwanto

Keyword(s):

Survival Rate ◽

Whole Blood ◽

Peripheral Blood ◽

Rattus Norvegicus ◽

Cecal Ligation ◽

Interleukin 1Β ◽

Cecal Ligation And Puncture ◽

Caspase 1

Sepsis masih merupakan salah satu penyebab kematian tertinggi di ruang rawat intensif. Mekanisme sepsis belum diketahui secara penuh. Perlunya metode-metode baru dalam penanganan sepsis. Penelitian-penelitian baru menemukan adanya peran dari Nod-like Receptor dan inflammasome. Chloroquine menunjukkan hasil yang cukup menjanjikan. Penelitian ini bertujuan untuk mengetahui pengaruh qloroquin terhadap interleukin-1β, aktivasi caspase-1 dan survival rate pada tikus model sepsis. Penelitian adalah eksperimen hewan coba (Rattus norvegicus) yang disepsiskan dengan Cecal Ligation and Puncture (CLP). Sampel 52 tikus, dibagi menjadi 2 kelompok; Kelompok 1 untuk IL-1β dan kelompok 2 aktivasi Caspase-1. Tiap kelompok dibagi 3 sub kelompok; kontrol tanpa CLP + placebo (NaCl 0.9% 2ml), perlakuan dengan CLP + placebo, dan kelompok terapi dengan CLP +Chloroquine (CHQ) 50mg/Kg BB personde. Terapi dan placebo diberikan 24, 48 dan 72 Jam setelah CLP. Tikus mati dan moribund dicatat sebagai mortalitas. Pada hari ke 6, tikus yang hidup diambil darahnya dan dikorbankan dengan dislokasi servikal. Kadar IL-1β dengan ELISA pada serum, Aktivasi Caspase-1 dengan Flowcytometry dengan pewarnaan FLICA 660 pada Peripheral Blood Mono-Nuclear Cells (PBMC) dan Whole Blood (WB). Analisis dengan SPSS 22. Beda rerata masing-masing subkelompok dianalisa dengan ANOVA bila distribusi normal dan atau uji Kruskal-Wallis dilanjutkan dengan Mann–Whitney.Hasil penelitian menunjukkan tidak adanya perbedaan survival rate yang bermakna antar sub-kelompok dan antar kelompok (mean 52 vs 62, CI: (-37.32) - 27.98, P=0.767). Didapatkan rerata kadar IL-1β yang lebih rendah pada kelompok terapi dibanding kelompok perlakuan (mean 0.08975 vs 0.09680 CI: (-0.024) – 0.0097, P=0,376), namun tidak bermakna secara statistik. Rerata tingkat aktivasi Caspase-1 pada PBMC (mean 9,46 vs 15.04 CI: (-6.72) – 24.82 , P=0.865) dan WB (mean 2,99 vs 10,99 CI: (-5.303) – 5.844, P=0.478) lebih rendah pada kelompok terapi dibanding perlakuan walaupun tidak bermakna secara statistik. Penelitian ini menunjukkan bahwa penghambatan kadar inflamasi tidak berhubungan langsung dengan survival rate. Mekanisme anti-inflamasi Chloroquine, salah satunya, tampak melewati jalur inflammasome. Kata kunci: Sepsis, Chloroquine, Inflammasome, Caspase-1, IL-1β, Survival rate.

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Can the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis?

Infection and Immunity ◽

10.1128/iai.00942-19 ◽

2020 ◽

Vol 88 (9) ◽

Cited By ~ 2

Author(s):

John C. Alverdy ◽

Robert Keskey ◽

Renee Thewissen

Keyword(s):

Cecal Ligation ◽

Human Microbiome ◽

Disease Process ◽

Underlying Disease ◽

Human Condition ◽

National Institutes Of Health ◽

Cecal Ligation And Puncture ◽

Human Sepsis ◽

Compare And Contrast ◽

Puncture Model

ABSTRACT A recent report by the National Institutes of Health on sepsis research has implied there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its therapeutic direction. As there have been many criticisms of the model, particularly regarding its relevance to human disease, how this model might be repurposed to be more reflective of the human condition begs discussion. In this piece, we compare and contrast the mouse microbiome of the CLP model to the emerging science of the microbiome of human sepsis and discuss the relevance for mice to harbor the specific pathogens present in the human microbiome during sepsis, as well as an underlying disease process to mimic the characteristics of those patients with undesirable outcomes. How to repurpose this model to incorporate these “human factors” is discussed in detail and suggestions offered.

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