Effects of hypertension and pulsatile flow in endothelial function of human saphenous veins in in vitro assay

• Grant number: 09/04731-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2010
• End date: November 30, 2010
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Paulo Roberto Barbosa Evora
• Grantee: Marina Junqueira Ferreira Rosique
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Despite of the wide use in revascularization surgery, the great safena vein bypass grafts have shorter patency than the arterial ones. This is due, in part, to the fact that the normal saphenous vein wall has different structural and functional characteristics that can be affected by high distention pressures during the vein harvesting or by its insertion in the arterial system. On implantation into the arterial circulation, a vein graft is subjected to dramatic changes in hemodynamic forces, being transplanted from a nonpulsatile, lowpressure, low-flow environment with minimal shear stress to a high-pressure system with pulsatile flow and a resultant elevated shear. These changes can be responsible, at least in part, for functional and morphological alterations in vessel wall culminating in intima hyperproliferation and atherosclerotic degeneration, which contribute for early graft thrombosis. In a recent study performed at the Experimental Surgery Endothelial Function Laboratory of University of São Paulo - Ribeirão Preto, human great saphenous veins were distended in vitro with different pressures during short periods and submitted to endothelial evaluation. It was determined that pressures under 300 mmHg do not affect pharmacologically great saphenous vein, but generate endothelial dysfunction and can work as smooth muscle inflamatory stimulous. Based on these findings and following the present research line, this project was designed to study the endothelium of human great saphenous vein submitted to prolonged time pulsed flow and high pressure perfusion, using an experimental model in vitro. The main objectives of this project is to study functional and morphological changes induced by prolonged exposure to high hydrostatic pressures in pulsed flow in vitro, in human great saphenous veins harvested for bypass grafting. This study will include: 1) morphometrical analysis with high-resolution microscopy; 2) nitric oxide sinthase isoforms, CD34 and nitrotyrosine imunohistochemical analysis; 3) tissue malondialdehide determination, as oxidative stress expression; 4) tissue nitrite/nitrate determination in great saphenous veins segment. (AU)