CMR Assessment of endothelial damage and angiogenesis in porcine coronary arteries using gadofosveset

<p>Abstract</p> <p>Background</p> <p>Endothelial damage and angiogenesis are essential for atherosclerotic plaque development and destabilization. We sought to examine whether contrast enhanced cardiovascular magnetic resonance (CMR) using gadofosveset could show endothelial damage and neovessel formation in balloon injured porcine coronary arteries.</p> <p>Methods and Results</p> <p>Data were obtained from seven pigs that all underwent balloon injury of the left anterior descending coronary artery (LAD) to induce endothelial damage and angiogenesis. Between one - 12 days (average four) after balloon injury, in vivo and ex vivo T1-weighted coronary CMR was performed after intravenous injection of gadofosveset. Post contrast, CMR showed contrast enhancement of the coronary arteries with a selective and time-dependent average expansion of the injured LAD segment area of 45% (p = 0.04; CI₉₅= [15%-75%]), indicating local extravasation of gadofosveset. Vascular and perivascular extravasation of albumin (marker of endothelial leakiness) and gadofosveset was demonstrated with agreement between Evans blue staining and ex vivo CMR contrast enhancement (p = 0.026). Coronary MRI contrast enhancement and local microvessel density determined by microscopic examination correlated (ρ = 0.82, p < 0.001).</p> <p>Conclusion</p> <p>Contrast enhanced coronary CMR with gadofosveset can detect experimentally induced endothelial damage and angiogenesis in the porcine coronary artery wall.</p

Flow in the well: computational fluid dynamics is essential in flow chamber construction

A perfusion system was developed to generate well defined flow conditions within a well of a standard multidish. Human vein endothelial cells were cultured under flow conditions and cell response was analyzed by microscopy. Endothelial cells became elongated and spindle shaped. As demonstrated by computational fluid dynamics (CFD), cells were cultured under well defined but time varying shear stress conditions. A damper system was introduced which reduced pulsatile flow when using volumetric pumps. The flow and the wall shear stress distribution were analyzed by CFD for the steady and unsteady flow field. Usage of the volumetric pump caused variations of the wall shear stresses despite the controlled fluid environment and introduction of a damper system. Therefore the use of CFD analysis and experimental validation is critical in developing flow chambers and studying cell response to shear stress. The system presented gives an effortless flow chamber setup within a 6-well standard multidish