scholarly journals Dual One-Way Study of Sepsis Survivability Study in Rats Exposed to Cecal Ligation and Puncture with Propofol or Isoflurane

Author(s):  
Keita Ikeda ◽  
Hari Prasad Osuru ◽  
Robert H. Thiele

Abstract BACKGROUNDSeveral studies have also shown that short-term exposure to volatile anesthetic agents (VAA) affects proinflammatory pathways such as the cytokine response and provides a protective effect that improves the outcome of sepsis. In contrast, Propofol has been shown to have no protective effect on sepsis in murine and rat models and may increase morbidity and mortality. This study aimed to investigate the efficacy of longer-term exposure to anesthetics, isoflurane, and Propofol (72 hours).METHODSAnimals were randomized into four groups: Isoflurane during surgery followed by three days of 0.8% isoflurane (and Intralipid IV), Propofol during surgery and 314 ug/kg/hr Propofol for three days, isoflurane during surgery and Intralipid for three days, and Propofol during surgery and Intralipid for three days.After induction via Propofol or isoflurane, animals spontaneously ventilated via nose cone with 100% oxygen. Propofol or Intralipid was administered through a 22 gauge intravenous catheter inserted into the jugular vein. Sepsis was induced in the rats by performing cecal ligation and puncture (CLP) through a paramedian incision into the abdominal cavity. The surgical concentration of isoflurane was kept at 2%, Propofol was maintained at 800 ug/kg/hr maintenance. After the recovery and three days of exposure to Intralipid or anesthetic agents, the rats were allowed to roam free in an adequately vented, temperature and humidity-controlled cage with food and water ad libitum. Survival data were summarized using the Kaplan-Meier curve with Log-Rank test to determine significance.RESULTSLog-Rank test for postoperative anesthetic agent groups showed that rats that received isoflurane for three days survived longer than the 72-hour postoperative Propofol group (P = 0.0002). Within the postoperative, no anesthetic agent (control) group, the group that received isoflurane during surgery survived longer than the Propofol during surgery group (P = 0.0081). Within the postoperative Intralipid groups, the male rats did not perform well with Propofol against isoflurane (P = 0.2599).CONCLUSIONSExposure of rats to isoflurane may prolong survival in CLP as compared to exposure to Propofol. This was true for rats with limited exposure during surgery with no postoperative anesthetics and those receiving intraoperative isoflurane with postoperative isoflurane.

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  

Introduction: Abnormal levels of end-tidal carbon dioxide (ETCO 2 ) may reflect a derangement in perfusion, metabolism, or gas exchange. It is unclear if ETCO 2 can be used for fluid resuscitation (FR) compared with traditional mean arterial pressure (MAP) as an outcome predictor in sepsis. Hypothesis: Use of ETCO2 is better than MAP in guiding fluid resuscitation to improve lactate levels and microcirculatory blood flow in sepsis. Methods: Thirty-five male Sprague-Dawley rats weighing 350-400g were randomized to: 1) SHAM, n=5; 2) cecal ligation and puncture (CLP) Control group (with CLP, without FR, n=10); 3) ETCO 2 group (with CLP, FR began when ETCO 2 ≤25 mmHg, n=10) and 4) MAP group (with CLP, FR began when MAP≤100 mmHg, n=10). Lactate level, cardiac output (CO), perfused small vessel density (PSVD) and sublingual microvascular flow index (MFI) was assessed at baseline, 2 h, 4 h, 8 h, 10 h and 12 h post-CLP. Survival duration was recorded. Results: After FR,CO in the ETCO 2 group increased compared with the MAP group 12h after CLP while lactate levels decreased compared with the Control and MAP groups (p<0.05) (Figure-1). Both sublingual PSVD and MFI decreased after CLP in the control group and MAP group but significantly improved in the ETCO 2 group 8h post-CLP. The average survival time in the ETCO 2 group was significantly greater than MAP group (Figure-2). Conclusions: ETCO 2 guided FR was associated with improved CO, lactate, microcirculatory flow, and survival time compared to MAP guided FR in a CLP-induced rat model of sepsis.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qian-wei Li ◽  
Qin Yang ◽  
Hong-Yang Liu ◽  
Yu-ling Wu ◽  
Yu-Hua Hao ◽  
...  

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis.


2011 ◽  
Vol 28 (7) ◽  
pp. 655-662 ◽  
Author(s):  
Mohamed Makni ◽  
Yassine Chtourou ◽  
Mohamed Barkallah ◽  
Hamadi Fetoui

This study investigated the protective effects of vanillin against acute brain damage induced by carbon tetrachloride (CCl4) in rats. The study was performed on 32 male rats divided into four groups: a control group, vanillin group ([Va] 150 mg/kg/day, intraperitoneally [i.p.]) and CCl4 toxication groups received a single injection of CCl4 (1 ml/kg, i.p.; CCl4 and Va + CCl4 groups). The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, glutathione transferase, glutathione peroxidase and nitric oxide (NO). Vanillin showed a significant brain-protective effect by decreasing the level of lipid peroxidation and NO2 and elevated the activities of antioxidative enzymes and level of GSH. Consequently vanillin blocked oxidative brain damage induced by CCl4 in rats.


2020 ◽  
Vol 19 (3) ◽  
pp. 270-276
Author(s):  
Jianying Wang ◽  
Xiaoting Yu

Acute kidney injury is a severe complication of sepsis. We have shown a protective effect of Platycodin D on sepsis induced acute kidney injury in an animal model that employs cecal ligation and puncture. Cecal ligation and puncture induced a series of degenerative changes in kidney, such as edema, hyperemia, and expansion in glomerular capillary, and inflammatory cells infiltration that were attenuated by Platycodin D. Also, rise in proinflammatory cytokine levels in septic rats was blunted by Platycodin D. Furthermore, Platycodin D administration reduced rise in serum levels of kidney injury markers-blood urea nitrogen and serum creatinine-in septic rats. Moreover, Platycodin D administration also suppressed the cell apoptosis in kidney that was associated with enhanced B-cell lymphoma 2 protein and reduced cleaved cysteine-aspartic protease-3 and BCL2-associated X protein. Lastly, Platycodin D administration attenuated sepsis-induced increase of phospho (p)-extracellular signal-regulated kinase, p-c-Jun NH2-terminal kinase, and p-p38. In conclusion, Platycodin D demonstrated protective effect against sepsis induced acute kidney injury through inactivation of mitogen activated protein kinase pathways, thus providing promising therapeutic strategy for the treatment of sepsis.


2005 ◽  
Vol 31 (6) ◽  
pp. 865-870 ◽  
Author(s):  
Hulya Babayigit ◽  
Can Kucuk ◽  
Erdogan Sozuer ◽  
Cevad Yazici ◽  
Kader Kose ◽  
...  

2020 ◽  
Vol 39 (7) ◽  
pp. 906-919 ◽  
Author(s):  
YF Ibrahim ◽  
RR Fadl ◽  
SAE Ibrahim ◽  
MF Gayyed ◽  
AMA Bayoumi ◽  
...  

Sepsis is one of the most common causes of death among hospitalized patients. Activity of xanthine oxidase (XO), a reactive oxygen species-producing enzyme, is known to be elevated in septic patients. Our aim was to investigate the possible protective role of XO inhibitor, febuxostat (FEB), in a rat model of sepsis-induced liver and kidney injures. Adult male albino rats were divided into four groups ( n = 12 each): sham control, sham + FEB, cecal ligation and puncture (CLP), and CLP + FEB groups. FEB (10 mg/kg per os (p.o.)) was given once daily for 2 days and 30 min prior to laparotomy with CLP. CLP was associated with a high mortality rate accompanied by significant liver and kidney injuries indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels and confirmed by histopathological tissue injury. Moreover, there was an increase in neutrophil gelatinase-associated lipocalin, uric acid, malondialdehyde, and nitric oxide levels and with decreased superoxide dismutase activity and total antioxidant capacity. In addition, CLP caused increased expression of the inflammatory markers tumor necrosis factor alpha, interleukin 1beta protein levels, and nuclear factor kappa B immunoexpression. Finally, CLP operated rats exhibited an upregulation in the apoptotic mediators, caspase 3, and P-C-Jun N-terminal kinases (JNK) proteins. FEB treatment of CLP rats caused a significant improvement and normalization in all measured parameters. Moreover, FEB amerliorates degenerative histopathological changes and improves the overall survival rate. In conclusion, FEB exhibited a protective effect in sepsis-induced liver and kidney injuries most probably through its anti-inflammatory, antioxidant, and antiapoptotic properties and attenuating JNK signaling pathway secondary to its XO enzyme inhibitory activity.


2018 ◽  
Vol 24 (3) ◽  
pp. 52-57
Author(s):  
V.M. Monastyrskyi

The evaluation of renal measurements such as length, width and thickness, volume is important in the diagnosis and treatment of many renal disorders, since there is a close relationship between the sizes of the kidneys and its function. The purpose of the study was to establish and compare during the postoperative period changes in the mass and sizes of the kidney left after nephrectomy in the sexually mature male rats. An experimental study was carried out on 84 sexually mature white male rats weighing 178-194 grams. Animals were divided into two groups: control (42 rats) and experimental (42 rats). In the control group, the animals under ketamine anesthesia were followed by an abdominal cavity dilution, after which the abdominal wall was applied in a row. All animals of the experimental group performed surgical intervention – nephrectomy of the left kidney. The animals were withdrawn from the trial by intra-pleural administration of thiopental-sodium 50 mg/kg after 7, 14, 21, 30, 90 days after nephrectomy. Macroscopic evaluation and description of the kidneys of animals was performed after their removal. Their weight was determined on the laboratory scale of HLR-200 up to 0.1 mg, and the length, width and thickness of the organ were measured with the help of a caliper to an accuracy of 0.05 mm. Calculated the volume of the kidney. The statistical analysis of the obtained results was carried out using the program STATISTICA 5.5 using parametric methods for evaluating the results. It was established that the mass, length, width, thickness and volume of the kidney of animals in the experimental group, as compared with the control group, were statistically significantly higher in all terms of observation. The fraction of the growth of the width and thickness of the single kidney of animals in the experimental group compared with the control animals in the animals was statistically significantly greater than the proportion of kidney growth during the postoperative period. It was found that the largest increase in the mass and thickness of the kidney, as compared with the control group, was observed after 30 days of the postoperative period, and the greatest increase in the length and width of the kidney, as compared with the control group, was observed after 14 days of the postoperative period.


2021 ◽  
Vol 18 (6) ◽  
pp. 1161-1166
Author(s):  
Zhiwen Zhou ◽  
Xiang Ren ◽  
Aiping Li ◽  
Wensheng Zhou ◽  
Li Huang

Purpose: To investigate the protective effect of floroindole against cecal ligation and puncture (CLP)- induced sepsis, as well as the underlying mechanism of action. Methods: Thirty-five 10–week-old male Wistar rats weighing 190 - 210 g (mean: 200.00 ± 10.10 g) were used for this study. The rats were randomly assigned to seven groups of five rats each, viz, normal control group, and six CLP groups. The CLP groups were those subjected to cecal ligation and puncture (CLP). The first 5 CLP groups received 2, 4, 6, 8 or 10 mg/kg floroindole, respectively, 1 h after CLP, via intraperitoneal route (i.p.) while the 6th CLP group served as untreated control. Western blotting, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) were used for the assessment of the expression levels of tumor necrosis factor-α (TNF- α), interleukn-6 (IL-6), nucleotide-binding oligomerization domain 2 (NOD2) and p-NF-κB p65. Results: Cecal ligation and puncture (CLP) significantly and time-dependently upregulated the expressions of TNF-α, IL-6 and NOD2 in intestinal tissues of rats (p < 0.05). However, treatment with floroindole significantly, and dose-dependently down-regulated CLP-induced expressions of these proteins (p < 0.05). Treatment of rats with floroindole also significantly and dose-dependently inhibited CLP-induced phosphorylation of NF-κB p65 in rat ileum (p < 0.05). Conclusion: The results obtained in this study demonstrate that floroindole confers some degree of protection against CLP-induced sepsis via inhibition of NF-κB p65 phosphorylation.


2009 ◽  
Vol 2 (1) ◽  
pp. 39-44
Author(s):  
Dragica Stojanović ◽  
Ružica Ašanin ◽  
Milica Ninković ◽  
Živorad Malićević ◽  
Igor Stojanov

We induced clinical form of sepsis in rats by cecal ligation and perforation (CLP) with mixed and pure culture of bacteria, with the aim to monitor glucose concentration in sepsis. The trial was carried out on 104 male rats, Wistar strain, body mass 190 to 240 g. The rats were divided in four groups consisting of 28 animals, and a control group of 20 animals. The period of observations were 12, 24, 72 and 120 hours after surgical intervention. In the examined sepsis model, a significant hypoglycemic activity was noticed in early sepsis (12 and 24 hours), but in the group with mixed bacteria culture only after 72 hours. Hyperglycemia was registered in late sepsis (72 hours) in the group of rats where sepsis was caused by pure bacterial culture of Escherichia coli and Staphylococcus aureus, without statistic significance compared to the findings in the control group.


Author(s):  
E.Yu. Shapovalova ◽  
G.A. Demyashkin ◽  
M.Yu. Malanichev ◽  
D.A. Pogosyan ◽  
I.A. Zorin ◽  
...  

Currently, the problem of treating sepsis is acute. To study these morphological and functional changes, animal models are used, for example, a model of experimental peritonitis, cecal ligation and puncture (CLP). However, there is only insufficient research on the description of internal organ rearrangements, in particular, skin morphological picture. The aim of the study was to assess of changes in mice internal organs in case of sepsis modeling. Materials and Methods. The authors performed cecal ligation and puncture in mice (n=40) to form experimental peritonitis and severe sepsis. In the control group (n=10), a sham surgery was conducted: a midline laparotomy was followed by layer-by-layer deaf suturing of the surgical wound. Results. The authors observed CLP-induced disorders in all vital organs, especially in the liver (violation of the beam structure of the hepatic lobules with signs of balloon dystrophy and necrosis areas, leukocyte infiltration, plethora of sinusoids), kidneys (thinning of the visceral layer of the Bowman’s capsule, narrowing of the afferent arteriole lumen, balloon dystrophy of proximal and distal tubules, widespread disappearance of the brush border in nephrocytes) and the spleen (hyperplasia of the white pulp with a large number of apoptotic lymphocytes). Moreover, signs of mild inflammatory infiltration were observed in the skin. Conclusion. The morphological changes found during the study corresponded to the reaction of the test organs in sepsis. The proposed CLP method for experimental peritonitis can be used as a sepsis model. Keywords: sepsis, cecal ligation and puncture (CLP), skin, inflammation. В настоящий момент остро стоит проблема лечения сепсиса. Для изучения данных морфофункциональных изменений используют модели на животных, например модель экспериментального перитонита – лигирование и пункцию слепой кишки (cecal ligation and puncture, CLP). Однако исследований, касающихся описания перестроек внутренних органов, в частности морфологической картины кожного покрова, проведено явно недостаточно. Цель исследования. Морфологическая оценка изменений внутренних органов мышей в условиях моделирования сепсиса. Материалы и методы. У мышей (n=40) проводили лигирование и пункцию слепой кишки для формирования экспериментального перитонита (CLP) и тяжелого сепсиса. В контрольной группе (n=10) осуществляли «фиктивную» операцию – срединную лапаротомию с последующим послойным глухим ушиванием операционной раны. Результаты. Во всех жизненно важных органах наблюдали нарушения, индуцированные CLP, особенно в печени (нарушение балочного строения печеночных долек с признаками баллонной дистрофии и зонами некроза, лейкоцитарная инфильтрация, полнокровие синусоидов), почках (истончение висцерального листка капсулы Боумена–Шумлянского, сужение просвета приносящих артериол, баллонная дистрофия проксимальных и дистальных канальцев, повсеместное исчезновение щеточной каемки в нефроцитах) и селезенке (гиперплазия белой пульпы с наличием большого количества апоптотических лимфоцитов), а также отмечали признаки слабой воспалительной инфильтрации в коже. Заключение. Обнаруженные в ходе исследования морфологические изменения соответствуют реакции исследуемых органов при сепсисе. Предложенный метод CLP для создания экспериментального перитонита можно использовать в качестве модели сепсиса. Ключевые слова: сепсис, cecal ligation and puncture (CLP), кожа, воспаление.


Sign in / Sign up

Export Citation Format

Share Document