Abstract 330: LDK378 Attenuates Macro and Microcirculation in a Sepsis Rat Model Induced by Cecal Ligation and Puncture

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Weiwei Ge ◽  
Zhengfei Yang ◽  
Qiaohua Hu ◽  
Xuefen Liu ◽  
Qin Ling ◽  
...  
Keyword(s):  
Rat Model ◽  
Inflammatory Mediator ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Male Rats ◽  
Flow Index ◽  
Cecal Ligation And Puncture ◽  
Sublingual Microcirculation ◽  
Sepsis Model ◽  
Severe Infections

Background: Sepsis is a systemic inflammatory response syndrome caused by severe infections. Myocardial dysfunction has been associated with increased mortality in septic patients. Previous studies have demonstrated that LDK378, a second-generation ALK inhibitor, is a potential anti-inflammatory mediator. We investigated the effects of LDK378 on macro and microcirculation in a rat model of cecal ligation and puncture (CLP) induced sepsis. Hypothesis: LDK378 attenuates the deleterious effects of sepsis on macro- and micro- circulation in CLP induced septic rats. Method: Fifteen male rats weighing between 450-550g were randomized into three groups: Sham, CLP, and CLP+LDK378. Our rat sepsis model was induced by 50% cecum ligation and two punctures with a 20-gauge needle. LDK378 (20mg/kg) was administered intraperitoneal (IP) to animals at 0h, 24h and 48 hours after CLP operation in the CLP+LDK378 group. Cardiac output (CO), mean arterial pressure (MAP); sublingual microcirculation including perfused small vessel density (PVD) and microcirculatory flow index (MFI) were measured at 6h, 30h and 54h after CLP. Results: Significant reduction in CO, MAP, MFI and PVD were observed in both CLP and CLP+LDK378 groups at 6h, 30h and 54h. However, the levels of CO, MAP, MFI and PVD reduction were significantly better in the CLP+LDK378 group when compared with the CLP group at 30h and 54h after CLP. Conclusion: LDK378 attenuates macro and microcirculation parameters in our rat model of sepsis.

Abstract 320: End-Tidal Carbon Dioxide Can Guide Fluid Resuscitation in a Cecal Ligation and Puncture Induced Rat Model of Sepsis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Survival Time ◽  
Fluid Resuscitation ◽  
Rat Model ◽  
Cecal Ligation ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
End Tidal Carbon Dioxide ◽  
Lactate Levels ◽  
End Tidal

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.

Carbon monoxide improves haemodynamics during extracorporeal resuscitation in pigs

2019 ◽  
Vol 116 (1) ◽  
pp. 158-170 ◽  
Author(s):  
Jakob Wollborn ◽  
Christoph Steiger ◽  
Eva Ruetten ◽  
Christoph Benk ◽  
Fabian A Kari ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Myocardial Dysfunction ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Flow Index ◽  
Protective Effects ◽  
Ventricular Ejection Fraction ◽  
Sublingual Microcirculation ◽  
Extracorporeal Resuscitation

Abstract Aims Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism. Methods and results In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P &lt; 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P &lt; 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P &lt; 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response. Conclusions CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs.

Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats

Shock ◽  
2009 ◽  
pp. 1 ◽  
Author(s):  
Elif Cadirci ◽  
Berrin Zuhal Altunkaynak ◽  
Zekai Halici ◽  
Fehmi Odabasoglu ◽  
M. Hamidullah Uyanik ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lipoic Acid ◽  
Cecal Ligation ◽  
Alpha Lipoic Acid ◽  
Cecal Ligation And Puncture ◽  
Potential Target ◽  
Sepsis Model

scholarly journals EXAMINATION OF GLUCOSES CONCENTRATION IN CHRONIC SEPSIS MODEL IN RATS

2009 ◽  
Vol 2 (1) ◽  
pp. 39-44
Author(s):  
Dragica Stojanović ◽  
Ružica Ašanin ◽  
Milica Ninković ◽  
Živorad Malićević ◽  
Igor Stojanov
Keyword(s):  
Cecal Ligation ◽  
Male Rats ◽  
Control Group ◽  
Clinical Form ◽  
Sepsis Model ◽  
Wistar Strain ◽  
Pure Bacterial Culture ◽  
Mixed Bacteria ◽  
Bacteria Culture ◽  
And Staphylococcus Aureus

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.

scholarly journals Volatile Anesthetics Improve Survival after Cecal Ligation and Puncture

2013 ◽  
Vol 119 (4) ◽  
pp. 901-906 ◽  
Author(s):  
Inge K. Herrmann ◽  
Maricela Castellon ◽  
David E. Schwartz ◽  
Melanie Hasler ◽  
Martin Urner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cecal Ligation ◽  
Volatile Anesthetics ◽  
Study Data ◽  
Cecal Ligation And Puncture ◽  
Immunomodulatory Effects ◽  
Organ Function ◽  
Minimal Alveolar Concentration ◽  
Sepsis Model ◽  
Sepsis Induction

Abstract Background: Sepsis remains a leading cause of death in intensive care units. There is growing evidence that volatile anesthetics have beneficial immunomodulatory effects on complex inflammation-mediated conditions. The authors investigated the effect of volatile anesthetics on the overall survival of mice in a sepsis model of cecal ligation and puncture (CLP). Methods: Mice (N = 12 per treatment group) were exposed to anesthetic concentrations of desflurane, isoflurane, and sevoflurane either during induction of sepsis or when the mice showed pronounced symptoms of inflammation. Overall survival, as well as organ function and inflammation was compared with the CLP group without intervention. Results: With desflurane and sevoflurane conditioning (1.2 minimal alveolar concentration for 2 h immediately after induction of CLP) overall survival was improved to 58% and 83%, respectively, compared with 17% in the untreated CLP group. Isoflurane did not significantly affect outcome. Application of sevoflurane 24 h after sepsis induction significantly improved overall survival to 66%. Conclusions: Administration of the volatile anesthetics desflurane and sevoflurane reduced CLP-induced mortality. Anesthesia may be a critical confounder when comparing study data where different anesthesia protocols were used.

CD123 thioaptamer protects against sepsis via the blockade between IL-3/CD123 in a cecal ligation and puncture rat model

2020 ◽  
Vol 40 (1) ◽  
pp. 16-31
Author(s):  
Jiangang Zhao ◽  
Meng Wang ◽  
Ying Yang ◽  
Guoxia Wang ◽  
Fengyu Che ◽  
...  
Keyword(s):  
Rat Model ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture
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