[Transmyocardial laser revascularization--an innovative pathophysiologic concept].

In patients with coronary artery disease where standard revascularization procedures are not appropriate, transmyocardial laser revascularization (TMLR) represents an innovative technique which is currently validated worldwide. Initially, it has been assumed that myocardial perfusion of ischemic regions could be instantly improved by inducing TMLR channels, which, however, might not be confirmed in ongoing studies. Indeed, the gain in O2 diffusion surface obtained by 20 patent TMLR channels is only 6 cm2 which accounts for just 0.01% of the total capillary surface (47000 cm2) of the myocardium. Instead, a chronic structural remodeling of myocardial regions, adjacent to TMLR channels and mediated by TMLR-induced expression of vascular endothelial growth factor (VEGF), may occur leading to neocapillarization of ischemic myocardium irrespective of the long-term patency of TMLR channels and, thereby, would improve myocardial perfusion (Figure 1). Six weeks following TMLR in the pig, patent TMLR channels were not observed. Instead, a marked degree of reparative fibrosis was found at the site of TMLR-treated myocardial regions (Figure 2). It is, however, not known, whether ischemic conditions would affect chronic channel patency. TMLR combined with intramyocardial administration of 0.5 microgram VEGF between the laser-induced channels resulted in few patent channels (Figure 3). The apparently low efficacy of VEGF applied as protein could be attributed to degradation of VEGF by local peptidases. In addition to VEGF, other growth factors and the interaction of endothelial cells and the extracellular matrix need to be considered. Of particular relevance appears alpha v beta 3-integrin which is needed for adhesion of endothelial cells to extracellular matrix components and is, therefore, 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 vessels. Thus, the expression of VEGF and alpha V beta 3-integrin in myocardial regions surrounding TMLR channels appears to be of major importance for the development of neoangiogenesis within the ischemic myocardium. Whether concomitant therapeutical strategies, i. e., gene transfer leading to over-expression of VEGF, will optimize the TMLR procedure by improving neoangiogenesis remains to be elucidated in future experimental studies.