title: Laser myocardial revascularization modulates expression of angiogenic, neuronal, and inflammatory cytokines in a porcine model of chronic myocardial ischemia.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Research Institute,Washington Hospital Center, Washington, DC 20010, USA. shmuel.fuchs@medstar.net
authors.forename: Shmuel
authors.initials: S
authors.lastname: Fuchs
authors.forename: Richard
authors.initials: R
authors.lastname: Baffour
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Matie
authors.initials: M
authors.lastname: Shou
authors.forename: Eugenio
authors.initials: E
authors.lastname: Stabile
authors.forename: Fermin O
authors.initials: FO
authors.lastname: Tio
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.forename: Ran
authors.initials: R
authors.lastname: Kornowski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003196:Computer Graphics; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007150:Immunohistochemistry; D053685:Laser Therapy / Q000379:methods*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009204:Myocardial Revascularization / Q000379:methods*; D018919:Neovascularization, Physiologic; D020932:Nerve Growth Factor / Q000378:metabolism; D010865:Pilot Projects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D013552:Swine
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D016222:Fibroblast Growth Factor 2; D020932:Nerve Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor