Browsing by Author "Byrd, James P."

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    Epicardial adipose excision slows the progression of porcine coronary atherosclerosis
    (Springer Nature, 2014-01-03) McKenney, Mikaela L.; Schultz, Kyle A.; Boyd, Jack H.; Byrd, James P.; Alloosh, Mouhamad; Teague, Shawn D.; Arce-Esquivel, Arturo A.; Fain, John N.; Laughlin, M. Harold; Sacks, Harold S.; Sturek, Michael; Cellular and Integrative Physiology, School of Medicine
    Background: In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. Methods: Ossabaw miniature swine (n=9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3-5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. Results: Circumferential plaque length increased (p<0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D2 synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months. Conclusion: In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis.
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    Mesenteric Fat Cryolipolysis attenuates insulin resistance in the Ossabaw Swine Model of the Metabolic Syndrome
    (Elsevier, 2023) Mazor, Rafi; Babkin, Alex; Littrup, Peter J.; Alloush, Mouhamad; Sturek, Michael; Byrd, James P.; Hernandez, Edward; Bays, Harold; Grunvald, Eduardo; Mattar, Samer G.; Anatomy, Cell Biology and Physiology, School of Medicine
    Background: The rising prevalence of insulin resistance (IR), metabolic syndrome, and type 2 diabetes are associated with increases in abdominal mesenteric fat. Adipocytes are sensitive to low temperatures, making cryolipolysis of mesenteric fat an attractive treatment modality to potentially reduce IR. Objectives: We aimed to determine whether (1) cryolipolysis is safe in reducing the volume of the mesenteric fat and (2) reduction in mesenteric fat volume reduces indices of IR and glycemic dysfunction. Setting: Indiana University School of Medicine. Methods: A novel cooling device and method delivered cryolipolysis in a controlled manner to avoid tissue ablative temperatures. Ossabaw pigs (n = 8) were fed a high-fat diet for 9 months to develop visceral obesity, IR, and metabolic syndrome. Following laparotomy, mesenteric fat cryolipolysis (MFC) was performed in 5 pigs, while 3 served as sham surgery controls. The volume of the mesenteric fat was measured by computed tomography and compared with indices of glucose intolerance before and at 3 and 6 months postprocedure. Results: MFC safely reduced mesenteric fat volume by ∼30% at 3 months, which was maintained at 6 months. Body weight did not change in either the MFC or sham surgery control groups. Measure of glycemic control, insulin sensitivity, and blood pressure significantly improved after MFC compared with sham controls. Conclusion: MFC reduces the volume of mesenteric fat and improves glycemic control in obese, IR Ossabaw pigs, without adverse effects.
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    Ossabaw Pig Demonstrates Detrusor Fibrosis and Detrusor Underactivity Associated with Oxidative Stress in Metabolic Syndrome
    (American Association for Laboratory Animal Science, 2020-10) Powell, Charles R.; Kim, Albert; Roth, Joshua; Byrd, James P.; Mohammad, Khalid; Khalid, Mouhamad; Alloosh, Mouhamad; Vittal, Ragini; Sturek, Michael; Urology, School of Medicine
    Metabolic Syndrome (MetS) has detrimental effects on the bladder, including detrusor underactivity. The progression and mechanism of disease are poorly understood. A swine model for diabetic bladder dysfunction (DBD) was established because of the pig's human-sized bladder and its ability to develop MetS by dietary modification alone. The hypothesis of this study is that this swine model will demonstrate oxidative stress associated with MetS, which contributes to both bladder fibrosis and detrusor underactivity (DU). Ossabaw pigs underwent dietary modification consisting of a hypercaloric, atherogenic diet for 10 mo to induce MetS, and were compared with a group of control (lean) pigs. Urodynamic studies were performed in both groups to confirm DU. Thiobarbituric acid reactive substances (TBARS) detected in the urine were used to measure oxidative stress activity in the urinary tract, and urinary IL17a was used to detect profibrotic activity. MetS was confirmed by assessing body weight, blood pressure, glucose tolerance, total cholesterol, and triglycerides. The MetS group exhibited an increase in the relative levels of urinary TBARS and IL17a. Bladder pressures at capacity were lower in the MetS group, suggesting DU. Histologic analysis of a cohort of control (lean) and MetS pigs revealed that as compared with the control pigs, the MetS pigs had significantly more collagen in the muscularis layer, but not in the submucosa or mucosa layer. In conclusion, the Ossabaw pig model for diet-induced MetS is associated with oxidative stress and profibrotic activity in the bladder, which results in DU. This has previously been shown in mice and rats, but never in pigs. This novel model will better represent human MetS and DBD because the mechanism and size of the pig bladder more closely resemble that of a human, resulting in a more valid model and facilitating further study into the signaling mechanisms responsible for this impairment.