33 Endovascular Brachytherapy

Endovascular Brachytherapy 637

Fig 32.1: Schematic drawing showing the cross-section of an arterosclerotic artery.

3 Vascular Pathology: Development of Restenosis and the Mechanism of Action of Radiotherapy 3.1 Pathology of restenosis In PTA/PTCA, the stenotic segment of the artery is dilatated using a special balloon catheter with pressure inflation from 14 - 18 atmospheres. This overstretching leads to a fracture of the atherosclerotic plaque and to significant damage in the different parts of the vessel wall (intima, media, (adventitia)), which may even result in a dissection of the wall at the time of intervention. The vessel wall with all its components has a complex reaction pattern to these injuries, which is partly similar to the complex wound healing process in other tissues (e.g. scar formation in the skin): * Neointimal proliferation. In reaction to the injury, platelets are deposited at the site of the lesion, forming a thrombus. Various cells are activated within hours (endothelial cells, platelets, smooth muscle cells) producing growth factors such as Interleukin, Platelet Derived Growth Factor (PDGF), and TGF beta. Within a few days, also mediated through activated Macrophages and T- Lymphocytes, this process leads to the activation of smooth muscle cells, myofibroblasts, and fibroblasts. Production of extracellular matrix is also activated. All these reactions finally lead to proliferation, migration, and differentiation of smooth muscle cells (media) and myofibroblasts (adventitia). Within weeks to months these cells migrate into the inner intimal layer of the vessel and form the “neointimal proliferation”. This process begins within days after angioplasty and continues for weeks and months. The reduction in synthesis of EDRF (Endothelium Derived Relaxing Factor) due to endothelial injury may also contribute to neointimal proliferation. The result of this neointimal proliferation is a severe reduction of the artery diameter. The whole process seems to be completed within 3 - 8 months. For a comprehensive understanding of the process of restenosis, two further mechanisms after PTA/PTCA must be considered: * Elastic recoil or shrinking of the artery occurs soon after dilatation of the artery. Recoil occurs within minutes and hours after angioplasty and leads to a loss of up to 50% of the vessel diameter, especially in the part of the vessel that was not arteriosclerotic before angioplasty. Elastic recoil cannot take place in stented arteries.