standardized-colon-ascendens-stent-peritonitis-rats-simple-feasible

Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury

AKI in septic patients is associated with increased mortality and poor outcome despite major efforts to refine the understanding of its pathophysiology. ...

University of Würzburg

Breakdown of microvascular endothelial barrier functions contributes to disturbed microcirculation, organ failure, and death in sepsis. Increased endothelial cAMP levels by systemic application of phosphodiesterase 4 inhibitors (PD-4-I) have previously been demonstrated to protect microvascular barrier properties in a model of systemic inflammation (systemic inflammatory response syndrome) suggesting a novel therapeutic option to overcome this problem. However, in a clinically relevant model of polymicrobial sepsis long-term effects, immunomodulatory effects and effectivity of PD-4-I to stabilize microvascular barrier functions and microcirculation remained unexplored.

Phosphodiesterase 4 inhibition dose dependently stabilizes microvascular barrier functions and microcirculation in a rodent model of polymicrobial sepsis.

To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation.

Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression.

Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring.

Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model.

Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6 h. After 24 h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1-4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion.

Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation.

Endothelial barrier dysfunction is a hallmark in the pathogenesis of sepsis. Sphingosine-1-phosphate (S1P) has been proposed to be critically involved in the maintenance of endothelial barrier function predominately by activating S1P receptor-1 (S1P1). Previous studies have shown that the specific S1P1 agonist SEW2871 improves endothelial barrier function under inflammatory conditions. However, the effectiveness of SEW2871 and potential side effects remained largely unexplored in a clinically relevant model of sepsis. Therefore, this study aimed to evaluate the effects of SEW2871 in the Colon ascendens stent peritonitis (CASP) model.

Sphingosine-1-Phosphate Receptor-1 Agonist Sew2871 Causes Severe Cardiac Side Effects and Does Not Improve Microvascular Barrier Breakdown in Sepsis.

In the surgical treatment of adrenocortical carcinoma (ACC), lymphadenectomy may improve oncologic outcome. However, patterns of metastatic lymphatic spread in ACC are unknown.

Patterns of Lymph Node Recurrence in Adrenocortical Carcinoma: Possible Implications for Primary Surgical Treatment.

Despite a growing body of evidence from randomized controlled studies, register data and meta-analyses, there is an ongoing controversy about decontamination of the digestive tract before elective colorectal surgery. Currently, mechanical bowel preparation alone can no longer be recommended as there is a lack of evidence for an advantage in terms of risk reduction for infectious complications, anastomotic leakage, morbidity and mortality. In contrast, the administration of oral antibiotics in addition to the obligatory intravenous single shot antibiotic prophylaxis has shown an additive reduction of the risk of up to 50% for the occurrence of postoperative infectious complications; however, due to a lack of data it is unclear if mechanical bowel preparation could even improve the positive effects of combined intravenous and oral antibiotics. Therefore, further studies are necessary. At the current time the occurrence of anastomotic leakage cannot be prevented, independent of whether preoperative bowel decontamination is performed.

[Oral antibiotic prophylaxis for bowel decontamination before elective colorectal surgery : Current body of evidence and recommendations].

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeons have had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards.

Surgery in times of COVID-19-recommendations for hospital and patient management.

Despite the development and introduction of new pharmaceutical approaches for Crohn's disease, the treatment of these patients still remains a major clinical challenge due to the heterogeneity in the course, degree of inflammation and localization. Over the last decade surgery was mainly reserved for the treatment of complications during the long course of Crohn's disease; however, due to new evidence-based knowledge, primary surgical resection in patients suffering from isolated Crohn's disease of the terminal ileum represents an equally effective alternative to medicinal antibody-based treatment. Even if further randomized and controlled trials are necessary, the currently available follow-up studies show promising data regarding disease progression with a significant reduction in the need for immunosuppression, which is usually necessary in these patients primarily treated by medication. Therefore, in the interdisciplinary decision on treatment early/primary surgical treatment should be considered as an equally effective alternative for a suitable patient collective.

[Terminal ileitis in Crohn's disease-Is primary surgery the better treatment?]

Gastric pull-up (GPU) procedures may be complicated by leaks, fistulas, or stenoses. These complications are usually managed by endoscopy, but in extreme cases multidisciplinary management including reoperation may be necessary. Here, we report a combined endoscopic and surgical approach to manage a failed secondary GPU procedure.

Managing esophagocutaneous fistula after secondary gastric pull-up: A case report.

Gastric pull-up after esophagectomy is still a demanding surgical procedure and associated with considerable morbidity such as anastomotic leaks, fistulas or stenoses. These complications are usually managed by endoscopy, but in extreme cases multidisciplinary management including reoperations may be necessary. Here, we report managing therapy-refractory pseudoachalasia after Ivor Lewis esophagectomy by bypassing colonic pull-up.

Successful management of therapy-refractory pseudoachalasia after Ivor Lewis esophagectomy by bypassing colonic pull-up: A case report.

Fewer Operations for Cancer in Germany During the First Wave of COVID-19 in 2020–A Cohort Study and Time-Series Analysis.

Patients with coronavirus disease 2019 (COVID-19) who undergo surgery have impaired postoperative outcomes and increased mortality. Consequently, elective and semi-urgent operations on the increasing number of patients severely affected by COVID-19 have been indefinitely postponed.in many countries with unclear implications on disease progression and overall survival. The purpose of this study was to evaluate whether the establishment of a standardized screening program for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficient to ensure high-quality medical and surgical treatment of COVID-19 and non-COVID-19 patients while minimizing in-hospital SARS-CoV-2 transmission.

Article	Year
Phosphodiesterase 4 inhibition dose dependently stabilizes microvascular barrier functions and microcirculation in a rodent model of polymicrobial sepsis. Shock (Augusta, Ga.)\| PubMed ID: 24569506	2014
Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression. Journal of pharmacology & pharmacotherapeutics\| PubMed ID: 25709347	2015
Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model. Intensive care medicine experimental\| PubMed ID: 26266931	2014
Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation. PloS one\| PubMed ID: 26340751	2015
Sphingosine-1-Phosphate Receptor-1 Agonist Sew2871 Causes Severe Cardiac Side Effects and Does Not Improve Microvascular Barrier Breakdown in Sepsis. Shock (Augusta, Ga.)\| PubMed ID: 28538086	2018
Patterns of Lymph Node Recurrence in Adrenocortical Carcinoma: Possible Implications for Primary Surgical Treatment. Annals of surgical oncology\| PubMed ID: 30443830	2019
[Oral antibiotic prophylaxis for bowel decontamination before elective colorectal surgery : Current body of evidence and recommendations]. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen\| PubMed ID: 31828386	2020
Surgery in times of COVID-19-recommendations for hospital and patient management. Langenbeck's archives of surgery\| PubMed ID: 32385568	2020
[Terminal ileitis in Crohn's disease-Is primary surgery the better treatment?] Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen\| PubMed ID: 33034699	2021
Managing esophagocutaneous fistula after secondary gastric pull-up: A case report. World journal of gastroenterology\| PubMed ID: 33967561	2021
Successful management of therapy-refractory pseudoachalasia after Ivor Lewis esophagectomy by bypassing colonic pull-up: A case report. World journal of clinical cases\| PubMed ID: 34141755	2021
Fewer Operations for Cancer in Germany During the First Wave of COVID-19 in 2020–A Cohort Study and Time-Series Analysis. Deutsches Arzteblatt international\| PubMed ID: 34491160	2021
Safety of elective abdominal and vascular surgery during the COVID-19 pandemic: a retrospective single-center study. European journal of medical research\| PubMed ID: 34556167	2021

Sven Flemming

Biography

JoVE Journal Publications

Other Publications