Biomedical subjects

David L Brown

Publications and source records attributed to David L Brown.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Tissue engineering of recellularized small-diameter vascular grafts.

A tissue-engineered small-diameter arterial graft would be of benefit to patients requiring vascular reconstructive procedures. Our objective was to produce a tissue-engineered vascular graft with a high patency rate that could withstand arterial pressures. Rat arteries were acellularized with a series of detergent solutions, recellularized by incubation with a primary culture of endothelial cells, and implanted as interposition grafts in the common femoral artery. Acellular grafts that had not been recellularized were implanted in a separate group of control animals. No systemic anticoagulants were administered. Grafts were explanted at 4 weeks for definitive patency evaluation and histologic examination; 89% of the recellularized grafts and 29% of the control grafts remained patent. Elastin staining demonstrated the preservation of elastic fibers within the media of the acellular grafts before implantation. Immunohistochemical staining of explanted grafts demonstrated a complete layer of endothelial cells on the lumenal surface in grafts that remained patent. Smooth muscle cells were observed to have repopulated the vessel walls. The mechanical properties of the matrix were comparable to native vessels. Such a strategy may present an alternative to autologous harvest of small vessels for use in vascular bypass procedures.

Animals↗

PubMedDate not supplied

Myocardial engineering in vivo: formation and characterization of contractile, vascularized three-dimensional cardiac tissue.

Engineering cardiac tissue in three dimensions is limited by the ability to supply nourishment to the cells in the center of the construct. This limits the radius of an in vitro engineered cardiac construct to approximately 40 microm. This study describes a method of engineering contractile three-dimensional cardiac tissue with the incorporation of an intrinsic vascular supply. Neonatal cardiac myocytes were cultured in vivo in silicone chambers, in close proximity to an intact vascular pedicle. Silicone tubes were filled with a suspension of cardiac myocytes in fibrin gel and surgically placed around the femoral artery and vein of adult rats. At 3 weeks, the tissues in the chambers were harvested for in vitro contractility evaluation and processed for histologic analysis. By 3 weeks, the chambers had become filled with living tissue. Hematoxylin and eosin staining showed large amounts of muscle tissue situated around the femoral vessels. Electron micrographs revealed well-organized intracellular contractile machinery and a high degree of intercellular connectivity. Immunostaining for von Willebrand factor demonstrated neovascularization throughout the constructs. With electrical stimulation, the constructs were able to generate an average active force of 263 microN with a maximum of 843 microN. Electrical pacing was successful at frequencies of 1 to 20 Hz. In addition, the constructs exhibited positive inotropy in response to ionic calcium and positive chronotropy in response to epinephrine. As engineering of cardiac replacement tissue proceeds, vascularization is an increasingly important component in the development of three-dimensional structures. This study demonstrates the in vivo survival, vascularization, organization, and functionality of transplanted myocardial cells.

Action Potentials↗

PubMedDate not supplied

Insulin-like growth factors and coronary heart disease.

Insulin-like growth factor-1 (IGF-I), the primary mediator of growth hormone (GH) effects, is an important regulator of cell growth, differentiation, and apoptosis. GH and IGF-I deficiency is known to be associated with premature atherosclerosis and elevated cardiovascular disease mortality. Recent evidence suggests that cardiovascular disease risk may also be elevated among apparently healthy individuals who have serum IGF-I levels in the low-normal range. In this review, we appraise the epidemiologic and clinical studies implicating low IGF-I level as a risk factor for incident myocardial infarction and other manifestations of coronary heart disease. Potential mechanisms that may underlie this association include beneficial effects of IGF-I on myocyte survival after ischemia, stability of atherosclerotic lesions, and endothelial function. We conclude that additional confirmatory data from prospective studies are needed to confirm low IGF-I level as an independent cardiovascular risk factor. However, if this finding is confirmed, this would support the rationale for intervention trials aimed at reducing cardiovascular disease morbidity and mortality among older adults by targeting the GH/IGF-I pathway.

Acute Disease↗

PubMedDate not supplied

Differences by age and race/ethnicity in knowledge about hypercholesterolemia.

This investigation sought to identify gaps in patients' knowledge about hypercholesterolemia and lipid-lowering therapy in an inner-city US population. Chart reviews and interviews were conducted for drug-treated hypercholesterolemic patients at 3 hospital-based cardiology practices in Bronx, NY. Univariate and multivariate analyses were used to assess whether race/ethnicity, sex, and age were predictors of knowledge. Subjects (n = 467, age 65.3 years) were 55% female, 38% Hispanic, 32% black, and 25% white. Most recognized hypercholesterolemia as a cause of heart disease (88%) and stroke (76%), although older subjects (>70 years) and Hispanic subjects, particularly non-English speakers, were significantly less likely to know about cardiovascular disease risks associated with hypercholesterolemia. Only 14% recalled their recent cholesterol levels, and recall was significantly lower among black, Hispanic, and older subjects. Overall, 31% expected to require lipid-lowering medications indefinitely in the future, while 66% did not know how long they would need to continue using medications. Blacks and Hispanics were significantly less likely to believe that they would need to continue taking medications indefinitely. Achieved lipid levels and self-reported medication adherence were relatively favorable although were unrelated to knowledge levels. In summary, among hypercholesterolemic patients in an urban population, relatively few knew their own cholesterol levels or expected to require medications indefinitely in the future. Older patients, black and Hispanic patients, and non-English speakers were significantly less likely to have accurate knowledge about hypercholesterolemia. Therefore, patient and community education efforts targeted to specific populations may lead to improved management of hypercholesterolemia in inner-city regions.

Adult↗