TRANSMYOCARDIAL LASER REVASCULARIZATION - A NOVEL PATHOPHYSIOLOGICAL CONCEPT

In patients with coronary artery disease where standard revascularizat ion procedures are not appropriate, transmyocardial laser revasculariz ation (TMLR) represents an innovative technique which is currently val idated worldwide. Initially, it has been assumed that myocardial perfu sion of ischemic regions could be instantly improved by inducing TMLR channels, which, however, might not be confirmed in ongoing studies. I ndeed, the gain in O-2 diffusion surface obtained by 20 patent TMLR ch annels is only 6 cm(2) which accounts for just 0.01% of the total capi llary surface (47000 cm(2)) of the myocardium. Instead, a chronic stru ctural remodeling of myocardial regions, adjacent to TMLR channels and mediated by TMLR-induced expression of vascular endothelial growth fa ctor (VEGF), may occur leading to neocapillarization of ischemic myoca rdium irrespective of the long-term patency of TMLR channels and, ther eby, would improve myocardial perfusion (Figure 1). Six weeks followin g TMLR in the pig, patent TMLR channels were not observed. Instead, a marked degree of reparative fibrosis was found at the site of TMLR-tre ated myocardial regions (Figure 2). It is, however, not known, whether ischemic conditions would affect chronic channel patency. TMLR VEGF b etween the laser-induced channels resulted in few patent channels (Fig ure 3). The apparently low efficacy of VEGF applied as protein could b e attributed to degradation of VEGF by local peptidases. In addition t o VECE other growth factors and the interaction of endothelial cells a nd the extracellular matrix need to be considered. Of particular relev ance appears alpha(v) beta(3)-integrin which is needed for adhesion of endothelial cells to extracellular matrix components and is, therefor e, required for neocapillarization. Among various other growth factors associated with neoangiogenesis, TGF-beta(1) and PDGF-BB are involved in the formation of extracellular matrix anchoring newly formed vesse ls. Thus, the expression of VEGF and alpha(v) beta(3)-integrin in myoc ardial regions surrounding TMLR channels appears to be of major import ance for the development of neoangiogenesis within the ischemic myocar dium. Whether concomitant therapeutical strategies, i.e., gene transfe r leading to overexpression of VEGF, will optimize the TMLR procedure by improving neoangiogenesis remains to be elucidated in future experi mental studies.