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Browsing by Author "Chen, Jun"
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Item A Mock Circulation Loop to Characterize In Vitro Hemodynamics in Human Systemic Arteries with Stenosis(MDPI, 2023) Hong, Weichen; Yu, Huidan; Chen, Jun; Talamantes, John; Rollins, Dave M.; Fang, Xin; Long, Jianyun; Xu, Chenke; Sawchuck, Alan P.; Surgery, School of MedicineVascular disease is the leading cause of morbidity and mortality and a major cause of disability for Americans, and arterial stenosis is its most common form in systemic arteries. Hemodynamic characterization in a stenosed arterial system plays a crucial role in the diagnosis of its lesion severity and the decision-making process for revascularization, but it is not readily available in the current clinical measurements. The newly emerged image-based computational hemodynamics (ICHD) technique provides great potential to characterize the hemodynamics with fine temporospatial resolutions in realistic human vessels, but medical data is rather limited for validation requirements. We present an image-based experimental hemodynamics (IEHD) technique through a mock circulation loop (MCL) to bridge this critical gap. The MCL mimics blood circulation in human stenosed systemic arterial systems that can be either 3D-printed silicone, artificial, or cadaver arteries and thus enables in vitro measurement of hemodynamics. In this work, we focus on the development and validation of the MCL for the in vitro measurement of blood pressure in stenosed silicone arteries anatomically extracted from medical imaging data. Five renal and six iliac patient cases are studied. The pressure data from IEHD were compared with those from ICHD and medical measurement. The good agreements demonstrate the reliability of IEHD. We also conducted two parametric studies to demonstrate the medical applicability of IEHD. One was the cardiovascular response to MCL parameters. We found that blood pressure has a linear correlation with stroke volume and heart rate. Another was the effect of arterial stenosis, characterized by the volumetric reduction (VR) of the arterial lumen, on the trans-stenotic pressure gradient (TSPG). We parametrically varied the stenosis degree and measured the corresponding TSPG. The TSPG-VR curve provides a critical VR that can be used to assess the true hemodynamic severity of the stenosis. Meanwhile, the TSPG at VR = 0 can predict the potential pressure improvement after revascularization. Unlike the majority of existing MCLs that are mainly used to test medical devices involving heart function, this MCL is unique in its specific focus on pressure measurement in stenosed human systemic arteries. Meanwhile, rigorous hemodynamic characterization through concurrent IEHD and ICHD will significantly enhance our current understanding of the pathophysiology of stenosis and contribute to advancements in the medical treatment of arterial stenosis.Item Cavopulmonary assist for the failing Fontan circulation: impact of ventricular function on mechanical support strategy(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-11) Giridharan, Guruprasad A.; Ising, Mickey; Sobieski, Michael A.; Koenig, Steven C.; Chen, Jun; Frankel, Steven C.; Rodefeld, Mark D.; Department of Surgery, IU School of MedicineMechanical circulatory support--either ventricular assist device (VAD, left-sided systemic support) or cavopulmonary assist device (CPAD, right-sided support)--has been suggested as treatment for Fontan failure. The selection of left- versus right-sided support for failing Fontan has not been previously defined. Computer simulation and mock circulation models of pediatric Fontan patients (15-25 kg) with diastolic, systolic, and combined systolic and diastolic dysfunction were developed. The global circulatory response to assisted Fontan flow using VAD (HeartWare HVAD, Miami Lakes, FL) support, CPAD (Viscous Impeller Pump, Indianapolis, IN) support, and combined VAD and CPAD support was evaluated. Cavopulmonary assist improves failing Fontan circulation during diastolic dysfunction but preserved systolic function. In the presence of systolic dysfunction and elevated ventricular end-diastolic pressure (VEDP), VAD support augments cardiac output and diminishes VEDP, while increased preload with cavopulmonary assist may worsen circulatory status. Fontan circulation can be stabilized to biventricular values with modest cavopulmonary assist during diastolic dysfunction. Systemic VAD support may be preferable to maintain systemic output during systolic dysfunction. Both systemic and cavopulmonary support may provide best outcome during combined systolic and diastolic dysfunction. These findings may be useful to guide clinical cavopulmonary assist strategies in failing Fontan circulations.Item Shifts in the Fecal Microbiota Associated with Adenomatous Polyps(American Association for Cancer Research, 2017-01) Hale, Vanessa L.; Chen, Jun; Johnson, Stephen; Harrington, Sean C.; Yab, Tracy C.; Smyrk, Thomas C.; Nelson, Heidi; Boardman, Lisa A.; Druliner, Brooke R.; Levin, Theodore R.; Rex, Douglas K.; Ahnen, Dennis J.; Lance, Peter; Ahlquist, David A.; Chia, Nicholas; Medicine, School of MedicineBACKGROUND: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. METHODS: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). RESULTS: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. CONCLUSIONS: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. IMPACT: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota.