cardiopulmonary-bypass-in-a-mouse-model-a-novel-approach

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

veno-venous-extracorporeal-membrane-oxygenation-in-a-mouse

Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for ...

Hannover medical school

Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine.

Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.

In this paper, we report on the interaction of multifunctional nanoparticles with living endothelial cells. The nanoparticles were synthesized using direct growth of gallium nitride on zinc oxide nanoparticles alloyed with iron oxide followed by core decomposition in hydrogen flow at high temperature. Using transmission electron microscopy, we demonstrate that porcine aortic endothelial cells take up GaN-based nanoparticles suspended in the growth medium. The nanoparticles are deposited in vesicles and the endothelial cells show no sign of cellular damage. Intracellular inert nanoparticles are used as guiding elements for controlled transportation or designed spatial distribution of cells in external magnetic fields.

Targeting Endothelial Cells with Multifunctional GaN/Fe Nanoparticles.

Vasa vasorum are blood microvessels which penetrate the adventitia and outer layers of the media of large blood vessels, supplying them with nutrients and oxygen. A growing body of evidence suggests that vasa vasorum play a central role in the pathogenesis of atherosclerosis. In this review, we will make a case for the role of microvascular dysfunction in the initiation of disease. When seen through this lens, new therapeutic opportunities for prevention can be envisioned. In particular, we discuss how targeting the cellular metabolism and epigenetic machinery of vasa vasorum neovessels could be harnessed to render vasa vasorum endothelial cells less sensitive to atherogenic stimuli.

Targeting vasa vasorum dysfunction to prevent atherosclerosis.

Cardiopulmonary bypass (CPB) is an essential component of many cardiac interventions, and therefore, there is an increasing critical demand to minimize organ damage resulting from prolonged extracorporeal circulation. Our goal was to develop the first clinically relevant mouse model of CPB and to examine the course of extracorporeal circulation by closely monitoring haemodynamic and oxygenation parameters.

Novel mouse model of cardiopulmonary bypass.

The emergence of multi-drug resistant bacteria threatens to end the era of antibiotics. Drug resistant bacteria have evolved mechanisms to overcome antibiotics at therapeutic doses and further dose increases are not possible due to systemic toxicity. Here we present a pilot study of ex vivo lung perfusion (EVLP) with high dose antibiotic therapy followed by autotransplantation as a new therapy of last resort for otherwise incurable multidrug resistant lung infections. Severe Pseudomonas aeruginosa pneumonia was induced in the lower left lungs (LLL) of 18 Mini-Lewe pigs. Animals in the control group (n = 6) did not receive colistin. Animals in the conventional treatment group (n = 6) received intravenous application of 2 mg/kg body weight colistin daily. Animals in the EVLP group (n = 6) had their LLL explanted and perfused ex vivo with a perfusion solution containing 200 μg/ml colistin. After two hours of ex vivo treatment, autotransplantation of the LLL was performed. All animals were followed for 4 days following the initiation of treatment. In the control and conventional treatment groups, the infection-related mortality rate after five days was 66.7%. In the EVLP group, there was one infection-related mortality and one procedure-related mortality, for an overall mortality rate of 33.3%. Moreover, the clinical symptoms of infection were less severe in the EVLP group than the other groups. Ex vivo lung perfusion with very high dose antibiotics presents a new therapeutic option of last resort for otherwise incurable multidrug resistant pneumonia without toxic side effects on other organs.

Treatment of infected lungs by ex vivo perfusion with high dose antibiotics and autotransplantation: A pilot study in pigs.

Plaque microvascularization and increased endothelial permeability are key players in the development of atherosclerosis, from the initial stages of plaque formation to the occurrence of acute cardiovascular events. First, endothelial dysfunction and increased permeability facilitate the entry of diverse inflammation-triggering molecules and particles such as low-density lipoproteins into the artery wall from the arterial lumen and vasa vasorum (VV). Recognition of entering particles by resident phagocytes in the vessel wall triggers a maladaptive inflammatory response that initiates the process of local plaque formation. The recruitment and accumulation of inflammatory cells and the subsequent release of several cytokines, especially from resident macrophages, stimulate the expansion of existing VV and the formation of new highly permeable microvessels. This, in turn, exacerbates the deposition of pro-inflammatory particles and results in the recruitment of even more inflammatory cells. The progressive accumulation of leukocytes in the intima, which trigger proliferation of smooth muscle cells in the media, results in vessel wall thickening and hypoxia, which further stimulates neoangiogenesis of VV. Ultimately, this highly inflammatory environment damages the fragile plaque microvasculature leading to intraplaque hemorrhage, plaque instability, and eventually, acute cardiovascular events. This review will focus on the pivotal roles of endothelial permeability, neoangiogenesis, and plaque microvascularization by VV during plaque initiation, progression, and rupture. Special emphasis will be given to the underlying molecular mechanisms and potential therapeutic strategies to selectively target these processes.

Vasa Vasorum Angiogenesis: Key Player in the Initiation and Progression of Atherosclerosis and Potential Target for the Treatment of Cardiovascular Disease.

Cardiopulmonary bypass (CPB) with moderate hypothermic cardiac arrest (MHCA) is essential for prolonged complex procedures in cardiac surgery and is associated with postoperative complications. Although cytokine release provoked through MHCA under CPB plays a pivotal role in postoperative organ damage, the pathomechanisms are unclear. Here, we investigated the cytokine release pattern and histological organ damage after MHCA using a recently described mouse CPB model. Eight BALB/c mice underwent 60 minutes of circulatory arrest under CPB, were successively rewarmed and reperfused. Blood cytokine concentrations and liver and kidney function parameters were measured and histological changes to these organs were compared to control animals. Our results showed a marked increase in proinflammatory cytokines and histological changes in the kidney, lung, and liver after CPB. Furthermore, clinical chemistry showed signs of hemolysis and acute kidney injury. These results suggest early onset of solid organ injury which correlates with increased leukocyte infiltration. A better understanding of the interplay between pro-inflammatory cytokine activation and solid organ injury in this model of CBP with MHCA will inform strategies to reduce organ damage during cardiac surgeries in the clinic.

Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass.

ArticleTotal : 2	Year
Publication title Cited by 9	2017
Publication title Cited by 10	2018

Article	Year
Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis. American journal of physiology. Gastrointestinal and liver physiology\| PubMed ID: 26564721	2016
Targeting Endothelial Cells with Multifunctional GaN/Fe Nanoparticles. Nanoscale research letters\| PubMed ID: 28799116	2017
Targeting vasa vasorum dysfunction to prevent atherosclerosis. Vascular pharmacology\| PubMed ID: 28830735	2017
Novel mouse model of cardiopulmonary bypass. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery\| PubMed ID: 28977367	2018
Treatment of infected lungs by ex vivo perfusion with high dose antibiotics and autotransplantation: A pilot study in pigs. PloS one\| PubMed ID: 29505574	2018
Vasa Vasorum Angiogenesis: Key Player in the Initiation and Progression of Atherosclerosis and Potential Target for the Treatment of Cardiovascular Disease. Frontiers in immunology\| PubMed ID: 29719532	2018
Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass. PloS one\| PubMed ID: 30308065	2018

Erin C. Boyle

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