Abstract P551: Platelet Activation is Associated with Pulmonary Edema and Renal Injury in a Rat Model of Polymicrobial Sepsis

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Jeanne Ishimwe ◽  
Maggie L McCalmon ◽  
Corbin A Shields ◽  
Ashley Gnam ◽  
Jan M Williams ◽  
...  
Keyword(s):  
Renal Function ◽  
Pulmonary Edema ◽  
Organ Dysfunction ◽  
Platelet Activation ◽  
Rat Model ◽  
Renal Injury ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Activated Platelets ◽  
Underlying Mechanisms

Sepsis, life-threatening organ dysfunction due to a dysregulated host response to infection, is positively correlated with platelet activation. Furthermore, clinical studies have also shown that platelet activation is associated with sepsis severity, suggesting a role for platelets in sepsis pathophysiology. Despite this correlation, the underlying mechanisms by which activated platelets contribute to sepsis are under investigated. In preliminary studies, we set out to determine if platelet activation is associated with multi-organ dysfunction and injury in a rat model of chronic polymicrobial abdominal sepsis. Sepsis was induced via cecal ligation and puncture (CLP) followed by cecum removal 24 hours post-CLP. At 72 hours post-CLP, blood, urine, and tissues were collected for analysis. Platelet activation was measured via flow cytometry. Lung wet/dry ratio and plasma creatinine were measured to assess lung edema and renal injury, respectively. Platelet activation doubled in CLP rats versus Sham rats. Activated platelets increased from 3.8±1.7% of the gated population in Sham animals (n=5) to 9.2±1.9% of the gated population in CLP animals (n=5; p=0.07). Lung wet/dry ratio significantly increased from 3.9±0.2 in Sham (n=8) to 6.7±1 in CLP rats (n=8; p<0.05). Furthermore, plasma creatinine increased by 33% from 0.55±0.3 mg/dL in Sham animals (n=6) to 0.73±0.06 mg/dL in CLP rats (n=8; p<0.05), indicating a decrease in renal function. These data demonstrate, for the first time, an increase in platelet activation in response to CLP, and identifies an association of activated platelets with pulmonary edema and reduced renal function in the cecal ligation and puncture rat model of abdominal polymicrobial sepsis. Future studies will investigate the underlying mechanisms by which activated platelets contribute to multi-organ dysfunction and injury in sepsis.

scholarly journals Platelet Inhibition Prevents NLRP3 Inflammasome Activation and Sepsis-Induced Kidney Injury

2021 ◽  
Vol 22 (19) ◽  
pp. 10330
Author(s):  
Marivee Borges-Rodriguez ◽  
Corbin A. Shields ◽  
Olivia K. Travis ◽  
Robert W. Tramel ◽  
Cedar H. Baik ◽  
...  
Keyword(s):  
Renal Function ◽  
Platelet Activation ◽  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Cecal Ligation ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Glomerular Injury ◽  
Activated Platelets ◽  
Nlrp3 Inflammasome Activation

Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to sepsis pathophysiology remains unclear. We previously demonstrated NOD-like receptor protein 3 inflammasome (NLRP3) inflammasome activation in sepsis-induced platelets from cecal-ligation puncture (CLP) rats. Activated platelets were associated with increased pulmonary edema and glomerular injury in CLP vs. SHAM controls. In this study, we investigated whether inhibition of platelet activation would attenuate NLRP3 activation and renal and pulmonary injury in response to CLP. CLP was performed in male and female Sprague Dawley (SD) rats (n = 10/group) to induce abdominal sepsis and SHAM rats served as controls. A subset of CLP animals was treated with Clopidogrel (10 mg/kg/day, CLP + CLOP) to inhibit platelet activation. At 72 h post-CLP, platelet activation and NLRP3 inflammasome assembly were evaluated, IL-1β and IL-18 were measured in plasma, and tissues, renal and pulmonary pathology, and renal function were assessed. Activated platelets were 7.8 ± 3.6% in Sham, 22 ± 6% in CLP and significantly decreased to 14.5 ± 0.6% in CLP + CLOP (n = 8–10/group, p < 0.05). NLRP3 inflammasome assembly was inhibited in platelets of CLP + CLOP animals vs. CLP. Significant increases in plasma and kidney IL-1β and IL-18 in response to CLP were decreased with Clopidogrel treatment. Renal injury, but not lung histology or renal function was improved in CLP + CLOP vs. CLP. These data provide evidence that activated platelets may contribute to sepsis-induced renal injury, possibly via NLRP3 activation in platelets. Platelets may be a therapeutic target to decrease renal injury in septic patients.

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.

scholarly journals Ramipril pretreatment worsened renal injury and survival despite a reduction in renal inflammation in experimentally induced sepsis in mice

2020 ◽  
Vol 21 (2) ◽  
pp. 147032032092397
Author(s):  
Tzvetanka Bondeva ◽  
Katrin Schindler ◽  
Claudia Schindler ◽  
Gunter Wolf
Keyword(s):  
Renal Function ◽  
Enzyme Inhibitor ◽  
Clinical Status ◽  
Cecal Ligation ◽  
Clinical Severity ◽  
Sham Operation ◽  
Cecal Ligation And Puncture ◽  
Renal Inflammation ◽  
Gene And Protein Expression ◽  
Experimentally Induced

Introduction: The angiotensin converting enzyme inhibitor ramipril is a standard antihypertensive therapy for many patients. Because angiotensin II may promote inflammation, we were interested in whether basal pretreatment with ramipril may modify renal function and inflammation as well as systemic outcome in experimentally induced sepsis in mice. Material and methods: Ramipril (10 mg/kg/day) pretreatment or placebo (NaCl) was given intraperitoneally for 5 days to C57BL6/J mice, followed by either sham operation or cecal ligation and puncture sepsis induction. Real-time polymerase chain reaction and immunological stains were used to evaluate renal gene and protein expression, respectively. Plasma creatinine, neutrophil-gelatinase associated lipocalin, and blood urea nitrogen were used as markers for renal function. A clinical severity score was determined. Results: Administration of ramipril before cecal ligation and puncture surgery was associated with reduced renal inflammation but did not improved renal function and structure and even worsened the clinical status of septic mice. Conclusions: The data suggest that the effects of ramipril pretreatment are complex. Additional studies including monitoring of hemodynamic parameters are necessary to elucidate the exact mechanism(s) of this observation. In addition, the timing of the ramipril administration could be of importance.

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

Changes of lymph metabolites in a rat model of sepsis induced by cecal ligation and puncture

2012 ◽  
Vol 73 (6) ◽  
pp. 1545-1552 ◽  
Author(s):  
Yan Li ◽  
Ming Hou ◽  
Jian-guang Wang ◽  
Tao Wang ◽  
Jian Wan ◽  
...  
Keyword(s):  
Rat Model ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture

scholarly journals Autonomic control in a rat model of sepsis induced by cecal ligation and puncture

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Glaucia Raquel Luciano Veiga ◽  
Lila Missay Oyama ◽  
Rubens Fazan ◽  
Roberto Pontes ◽  
Ruy Campos ◽  
...  
Keyword(s):  
Rat Model ◽  
Cecal Ligation ◽  
Autonomic Control ◽  
Cecal Ligation And Puncture

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.

Effects of End-Tidal Carbon Dioxide-Guided Fluid Resuscitation on Outcomes in a Cecal Ligation and Puncture Induced Rat Model of Sepsis

Shock ◽  
2019 ◽  
Vol 51 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Fluid Resuscitation ◽  
Rat Model ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
End Tidal Carbon Dioxide ◽  
End Tidal
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