Local endovascular treatment of aortic aneurysms. From operating theater to lab bench.

Current treatment of aortic abdominal aneurysms by conventional surgery or endoprosthesis is flawed by high post-operative mortality and unpredictable durability of haemodynamic exclusion, respectively. We have developed endovascular approaches with cell and gene transfer, aimed at controlling further diameter expansion in an animal model of already-developed aneurysms in rats. Preliminary results suggest that both cell and gene endovascular therapy can be used to control expansion of aneurysms generated by inflammation and proteolytic destruction of the aortic wall.

Pseudointima in inflow and outflow conduits of a left ventricular assist system: possible role in clinical outcome.

Activation of blood coagulation and thromboemboli have been shown to present significant clinical risks in patients supported with an left ventricular assist system (LVAS). The interaction of pseudointima (PI) with blood in the conduits of the device could be involved in these clinical complications. Our aim was to study the morphology of the PI versus duration of circulatory support. Novacor N 100 PC LVASs were explanted from 10 men and 2 women after a mean of 209 days (range 23-560 days) of circulatory assistance. PI in the inflow and outflow conduits were investigated with immunohistochemical assays. In the inflow conduits, a loosely adherent PI had built up from collagen type I and III fibers growing into and between fibrin deposits. Disorganized collagenous matrix and longitudinally oriented collagen fibers included alpha-smooth muscle actin positive cells with random orientation. Macrophages were concentrated in the fibrin and were dispersed throughout the extracellular matrix. In the outflow conduits, a thin, adherent PI was composed of regular collagen type I and III layers. Collagen type I fibers had grown into the woven Dacron and alpha-smooth muscle actin positive cells were oriented in the axis of the blood flow. Macrophages were concentrated in the Dacron and reached the inner collagen layers. Venous blood flow in the inflow conduits allows the development of a non endothelialized irregular collagenous matrix intermingled with fibrin and invaded by macrophages. These persistent structural features progress with duration of circulatory assistance and reflect matrix degradation and remodeling. The potential to release thromboembolic fragments from the non stable, thrombogenic PI may be involved in the thromboembolic or neurologic complications sustained by 5 of 12 patients who were on circulatory support for as long as 200 days.

Deterioration of bioprosthetic heart valves.

The aim of this study was to detect biologic factors in the structural deterioration of bioprosthetic heart valves. Prostheses were removed from patients after 4-8 years of implantation and submitted to biochemical and morphologic assays. Successive staining of biologic sections revealed colocalization of lipids and glycosaminoglycans underneath calcifications in the disintegrated extracellular matrix. On biochemical assays, the amidolysis of synthetic peptide substrates indicated thrombin, plasmin, and tissue plasminogen activator activities in the nonhemocompatible leaflets; 0.15 mol NaCl, 0.05 mol Tris, and 5 mmol CaCl2 extracts from the prostheses cleaved the peptide substrate for collagenase and lysed gelatin gels. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate disclosed the presence of low molecular mass polypeptides in extracts of the deteriorated prostheses. The detection of plasmin and collagenolytic enzyme(s), and the known broad proteolytic activity of plasmin, may point to the role of activation of the fibrinolytic system in the proteolytic degradation of bioprosthetic valves.