Laser myocardial revascularization modulates expression of angiogenic, neuronal, and inflammatory cytokines in a porcine model of chronic myocardial ischemia.

Abstract

Controversy exists whether transmyocardial laser revascularization (TMR) is associated with angiogenesis or neuromodulation and whether these are time-dependent phenomena. Accordingly, we performed a time-course analysis of the expression of angiogenic and neuronal factors following experimental percutaneous TMR. Five weeks after placing ameroid constrictors on the circumflex coronary artery, 16 pigs underwent left ventricular mapping guided TMR using Ho:YAG laser (2 J x 1 pulse) at 30 sites directed at the ischemic zones and 11 animals were ischemic controls. Histology and immunostaining were obtained at 1 and 2 weeks (4 TMR and 3 controls at each time point) and at 4 weeks (8 TMR and 5 controls) for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), nerve growth factor (betaNGF), substance P (SP), and monocyte chemoattractant protein-1 (MCP-1). Immunoreactivity was scored using a digital image analysis system. Factor VIII staining was used for blood vessel counting. Enhanced regional expression of VEGF, bFGF and MCP-1 in the TMR group was noted at 1 and 2 weeks with a threefold increase at 4 weeks following TMR compared to controls. BetaNGF expression in the TMR group was enhanced at 1 and 2 weeks with subsequent decline at 4 weeks to the controls level. SP expression was not significantly different between groups at all time points. There was a twofold increase in the number of blood vessels in the TMR group at 4 weeks, which was not apparent earlier. These immunohistological findings suggest that cytokines expression compatible with angiogenesis and neuromodulation occurs early after TMR. Up-regulation of angiogenic and inflammatory cytokines may be more sustained than neuromodulation.