scholarly journals Quick model of septic shock in rats

2016 ◽  
Vol 15 (1) ◽  
pp. 73-77
Author(s):  
D. V. Stroukov ◽  
A. G. Vasilev ◽  
Yu. S. Alexandrovich
Keyword(s):  
Septic Shock ◽  
Intravenous Infusion ◽  
Direct Method ◽  
Adequate Model ◽  
Fundamental Research ◽  
Few Data ◽  
Endothelial Growth Factor ◽  
Increased Activity ◽  
15Th Minute ◽  
Convenient Model

Modeling septic shock by means of administration of living bacteria is a minimum invasive adequate model for reproduction of this pathologic process, however there is a few data on effectiveness of this model in rats on the basis of direct measurement of hemodynamic parameters. The goal of the study was to elaborate a simple and convenient model of septic shock by intravenous infusion of living bifidobacteria. Indexes of central hemodynamics evaluated by direct method were analyzed in the study as well as endothelial function of blood vessels assessed by measuring concentration of NO, vessels' endothelial growth factor-A and tissue plasminogen activator. Dysfunction of hemostasis was also estimated by measuring fibrinogen level and soluble complexes of fibrin monomer. Intravenous infusion of living bifidobacteria caused development of severe septic shock by 15th minute after administration with valid decrease of all systemic hemodynamics' parameters. Marked hemodynamic disturbancies combined with development of endothelial dysfunction and hemostatic mechanisms' increased activity. The present model is absolutely safe; it can be easily reproduced in a research or training laboratory and it can be used for fundamental research of septic shock, for pre-clinical tests of drugs as well as for educational purposes.

No inducible synthase inhibitors produce a positive effect on indexes of central hemodynamics in rats with septic shock

2015 ◽  
Vol 6 (4) ◽  
pp. 45-50
Author(s):  
Danila Viktorovich Strukov ◽  
Andrey Glebovich Vasiliev ◽  
Yuriy Stanislavovich Alexandrovich
Keyword(s):  
Septic Shock ◽  
Intravenous Administration ◽  
Positive Impact ◽  
Direct Method ◽  
Laboratory Animals ◽  
Vascular Endothelial ◽  
Central Hemodynamics ◽  
Inos Inhibitors ◽  
Endothelial Growth Factor

The purpose of the study was to evaluate the efficacy of NO inducible synthase (iNOS) inhibitors involved in simulation of septic shock in rats. Model of septic shock (SS) was obtained in rats by intravenous administration of live Bifidobacteria culture. Aminoguanidine was used as a selective inhibitor of iNOS. Indexes of central hemodynamics measured by direct method where analyzed. Vascular endothelial function was rated by determination of nitric oxide (II) (NO), vascular endothelial growth factor A (VEGF-A) and tissue plasminogen activator (tPA) in plasma. Hemostatic parameters were evaluated by the level of soluble fibrin monomer complexes (RKMF). Intravenous administration of live Bifidobacteria culture in rats proved to cause an adequate and effective septic shock model with characteristic changes of hemodynamics in laboratory animals, development of endothelial dysfunction and hemostasis system activation in response to bacteremia. INOS inhibitors have a positive impact on hemodynamics in septic shock. NO is not the only factor in the development of hypotension in septic shock. INOS inhibitors appear to affect the extent of vasopressor dose utilized in the therapy of septic shock contributing to improvement of microcirculation and tissue oxygenation.

scholarly journals Ulinastatin as an Adjuvant Therapy to Restricting Volumes of Resuscitation Fluid Strategy for Patients with Septic Shock after Initial Management

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rensong Dong ◽  
Xi Zhang ◽  
Zhi Zhao
Keyword(s):  
Septic Shock ◽  
Adjuvant Therapy ◽  
Vascular Permeability ◽  
Fluid Resuscitation ◽  
Intravenous Infusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Thrombin Time ◽  
Pulmonary Vascular Permeability ◽  
Resuscitation Fluid

Septic shock is the most serious complication of sepsis, leading to unacceptably high morbidity and mortality worldwide. Fluid resuscitation using crystalloids has become the mainstay of early and aggressive treatment of severe sepsis and septic shock, while increased daily fluid balances from day 2 until day 7 have been related with increased mortality. Recently, pharmacological management has been recommended to combine with appropriate fluid resuscitation for the treatment of septic shock. In this study, we compared the clinical efficacy of restricting volumes of resuscitation fluid strategy with or without intravenous infusion of ulinastatin (UTI) in treating patients with septic shock and additionally examined the patient’s changes of the extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), systemic vascular resistance index (SVRI), cardiac function, lactic acid (LA) level, coagulation function, and renal function. The study included 182 patients with septic shock, among which 89 patients had undergone restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI and 93 patients had undergone restricting volumes of resuscitation fluid strategy alone. It was found that patients with septic shock after restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI showed an increased SVRI concomitant with declined PVPI and EVLWI, increased mean artery pressure (MAP), cardiac output (CO), left ventricular ejection fraction (LVEF), stroke volume (SV), and heart rate (HR), declined levels of cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP), reduced LA level along with shortened prothrombin time (PT) and partially activated thrombin time (PATT), and decreased levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) when comparable to those after restricting volumes of resuscitation fluid strategy alone ( P < 0.05 ). We also observed fewer scores of the Acute Physiology and Chronic Health Evaluation (APACHE II) and the sequential organ failure assessment (SOFA) in patients undergoing restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI than those undergoing restricting volumes of resuscitation fluid strategy alone ( P < 0.05 ). According to the above data, it is concluded that UTI as an adjuvant therapy for restricting volumes of resuscitation fluid strategy in treating septic shock may decrease the LA level, attenuate the inflammatory response, reduce vascular permeability, prevent pulmonary edema, and restore cardiac and renal functions.

scholarly journals Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients

2020 ◽  
Vol 21 (10) ◽  
pp. 3532 ◽  
Author(s):  
Francesca Pirini ◽  
Luigi Pasini ◽  
Gianluca Tedaldi ◽  
Emanuela Scarpi ◽  
Giorgia Marisi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Free Survival ◽  
Antiangiogenic Treatment ◽  
Tetranucleotide Repeats ◽  
Few Data ◽  
Colorectal Cancer Patients ◽  
Endothelial Growth Factor

Very few data are reported in the literature on the association between elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and prognosis in advanced colorectal cancer. Moreover, there is no information available in relation to the response to antiangiogenic treatment. We analyzed EMAST and vascular endothelial growth factor-B (VEGF-B) microsatellite status, together with standard microsatellite instability (MSI), in relation to prognosis in 141 patients with metastatic colorectal cancer (mCRC) treated with chemotherapy (CT) alone (n = 51) or chemotherapy with bevacizumab (B) (CT + B; n = 90). High MSI (MSI-H) was detected in 3% of patients and was associated with progression-free survival (PFS; p = 0.005) and overall survival (OS; p < 0.0001). A total of 8% of cases showed EMAST instability, which was associated with worse PFS (p = 0.0006) and OS (p < 0.0001) in patients treated with CT + B. A total of 24.2% of patients showed VEGF-B instability associated with poorer outcome in (p = 0.005) in the CT arm. In conclusion, our analysis indicated that EMAST instability is associated with worse prognosis, particularly evident in patients receiving CT + B.

scholarly journals Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock

2004 ◽  
Vol 72 (3) ◽  
pp. 1820-1823 ◽  
Author(s):  
Toshio Toyosawa ◽  
Mamoru Suzuki ◽  
Kohtarou Kodama ◽  
Seiichi Araki
Keyword(s):  
Septic Shock ◽  
Bacterial Infection ◽  
Intravenous Infusion ◽  
Sodium Phosphate ◽  
Therapeutic Strategy ◽  
Therapeutic Effects ◽  
Vitamin B2 ◽  
Gram Positive ◽  
Gram Negative ◽  
Sepsis And Septic Shock

ABSTRACT Highly purified vitamin B2 (riboflavin 5′-sodium phosphate; purity > 97%) treatment by intravenous infusion at doses above those used clinically to treat vitamin B2 deficiency showed therapeutic effects in mice not only in cases of endotoxin- and exotoxin-induced shock but also in cases of gram-negative and gram-positive bacterial infection even after the toxemia had already begun.

scholarly journals The Diagnostic and Prognostic Role of Vascular Endothelial Growth Factor C in Sepsis and Septic Shock

2020 ◽  
Vol 6 (3) ◽  
pp. 152-158
Author(s):  
Emoke Almasy ◽  
Janos Szederjesi ◽  
Bianca Liana Grigorescu ◽  
Iudita Badea ◽  
Marius Petrisor ◽  
...  
Keyword(s):  
Septic Shock ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Apache Ii ◽  
Vascular Endothelial ◽  
Severity Scores ◽  
The Mean ◽  
Factor C ◽  
Sepsis And Septic Shock ◽  
Endothelial Growth Factor

AbstractIntroductionVariations in the expression of vascular endothelial growth factor (VEGF) could be used as a biomarker in critically ill patients with sepsis and septic shock. Inflammation potently upregulates VEGF-C expression via macrophages with an unpredictable response. This study aimed to assess one of the newer biomarkers (VEGF-C) in patients with sepsis or septic shock and its clinical value as a diagnostic and prognostic tool.Material and methodsThe study involved 142 persons divided into three groups. Group A consisted of fifty-eight patients with sepsis; Group B consisted of forty-nine patients diagnosed as having septic shock according to the Sepsis -3 criteria. A control group of thirty-five healthy volunteers comprised Group C. Severity scores, prognostic score and organ dysfunction score, were recorded at the time of enrolment in the study. The analysis included specificity and sensitivity of plasma VEGF-C for diagnosis of septic shock. Circulating plasma VEGF-C levels were correlated with the APACHE II, MODS and severity scores and mortality.ResultsThe mean (SD) plasma VEGF-C levels in septic shock patients (1374(789) pg./m), on vasopressors at the time of admission to the ICU, were significantly higher 1374(789)pg./mL, compared the mean (SD) plasma VEGF-C levels in sepsis patients (934(468) pg./mL); (p = 0.0005, Student’s t-test.) Plasma VEGF-C levels in groups A and B were shown to be significantly correlated with the APACHE II (r = 0.21, p = 0.02; r = 0.45, p = 0.0009) and MODS score (r = 0.29, p = 0.03; r = 0.4, p = 0.003). There was no association between plasma VEGF-C levels and mortality [p = 0.1]. The cut-off value for septic shock was 1010 pg./ml.ConclusionsVEGF-C may be used as a prognostic marker in sepsis and septic shock due to its correlation with APACHE II values and as an early marker to determine the likelihood of developing MODS. It could be used as an early biomarker for diagnosing patients with septic shock.

scholarly journals Acetate Ringer's solution versus 0.9% saline for septic patients: study protocol for a randomized controlled multicenter crossover trial

2020 ◽  
Author(s):  
Fang Liu ◽  
Jing Zhang ◽  
Yuan Zhu ◽  
Lianjiu Su ◽  
Yiming Li ◽  
...  
Keyword(s):  
Septic Shock ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Intravenous Infusion ◽  
Crossover Trial ◽  
Kidney Injury ◽  
Hospital Death ◽  
Ringer’S Solution

Abstract Background: The previous study demonstrated that there were no significant differences between saline and balanced crystalloid solution infused in critical illness. However, the sepsis subgroup analysis showed the statistical difference. Thus, we will specifically focus on septic patients in this study to compare the effects of saline and balanced solution. We hypothesize that effects of saline on acute kidney injury (AKI) are related to the underline AKI severity and total volumes of infusion. Methods/design: The investigators designed a pragmatic, multi-centered crossover trial recruiting 312 patients who are diagnosed as sepsis/septic shock in the intensive care unit (ICU) and will be assigned with either acetate Ringer's solution or saline in the corresponding month. Patients with an end-stage renal disease (ESRD) or who need renal replacement therapy (RRT) prior to or at the time of enrollment are excluded. Enrolled patients will be regarded as with mild, moderate or severe sepsis on the basis of the severity of their illness, and will be divided into subgroups according to their initial renal function and various intravenous infusion volumes when being analyzed. The primary outcome is major adverse kidney events (MAKE), including the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction. Secondary outcomes include 28 days-mortality, internal environment disturbance, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, duration of RRT and ICU and hospital length of stay. Results and Conclusions: To our knowledge, this study will be the first to focus on septic patients and provide credible and evident data on the comparison of outcome between acetate Ringer’s solution and saline for intravenous infusion in adult septic patients on the basis of baseline renal function and infusion volumes taken into consideration. Trial registration: ClinicalTrials.gov, identifiers: NCT03685214. Registered on August 15, 2018. https://clinicaltrials.gov/ct2/show/NCT03685214 Keywords: sepsis; septic shock; acute kidney injury; saline; acetate Ringer's solution.

Vascular Endothelial Growth Factor in Severe Sepsis and Septic Shock

2008 ◽  
Vol 106 (6) ◽  
pp. 1820-1826 ◽  
Author(s):  
Sari Karlsson ◽  
Ville Pettilä ◽  
Jyrki Tenhunen ◽  
Vesa Lund ◽  
Seppo Hovilehto ◽  
...  
Keyword(s):  
Septic Shock ◽  
Vascular Endothelial Growth Factor ◽  
Severe Sepsis ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Sepsis And Septic Shock ◽  
Endothelial Growth Factor

Nitric oxide, VEGF, and VEGFR-2: interactions in activity-induced angiogenesis in rat skeletal muscle

2005 ◽  
Vol 289 (1) ◽  
pp. H336-H343 ◽  
Author(s):  
Malgorzata Milkiewicz ◽  
Olga Hudlicka ◽  
Margaret D. Brown ◽  
Haley Silgram
Keyword(s):  
Nitric Oxide ◽  
Nuclear Antigen ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Capillary Growth ◽  
Capillary Bed ◽  
Endothelial Growth Factor ◽  
Proliferating Cell ◽  
Increased Activity ◽  
Increased Blood Flow

Vascular endothelial growth factor (VEGF) is considered to be important in promotion of capillary growth in skeletal muscles exposed to increased activity. We studied its interactions with nitric oxide (NO) by examining the expression of endothelial NO synthase (NOS), VEGF, and VEGF receptor-2 (VEGFR-2) proteins in relation to capillary growth in rat extensor digitorum longus muscles electrically stimulated for 2, 4, or 7 days with and without NOS inhibition by Nω-nitro-l-arginine (l-NNA, 3 mg/day). Stimulation increased all proteins from 2 days onward, concomitantly with capillary proliferation (labeling for proliferating cell nuclear antigen). Capillary-to-fiber ratio was elevated by 25% after 7 days. Concurrent oral administration of l-NNA did not affect the increase in endothelial NOS but depressed its activity, as shown by increased blood pressure and decreased arteriolar diameters in 2-day-stimulated muscles. NOS inhibition eliminated the increased expression of VEGFR-2 and VEGF proteins in muscles stimulated for 2 and 4 days but not for 7 days. However, it depressed capillary proliferation and the increase in C/F at all time points. We conclude that, in stimulated muscles, NO, generated by activation of neuronal NOS by muscle activity or endothelial NOS by increased blood flow and capillary shear stress, may increase capillary proliferation in the early stages of stimulation through upregulation of VEGFR-2 and VEGF. With longer stimulation, capillary growth appears to require NO, and high levels of VEGF and VEGFR-2 may be contributing to maintenance of the increased capillary bed.

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