Background: Angiogenesis is the proposed mechanism of transmyocardial revascularization. We evaluated mechanical transmyocardial revascularization in a chronically ischemic porcine model by measuring myocardial angiogenic response. Methods: Ameroid constrictors were implanted 6 weeks before mechanical transmyocardial revascularization, Group I (n = 5) and group II (n = 3) animals received 30 punctures with an 18-gauge needle and samples were harvested at 1 and 4 weeks, respectively, after the operation. Group III (n = 5) had sternotomy only and served as the control group. Myocardial samples were immunohistochemically stained for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-beta) using specific antibodies. Growth factor expression was quantified by means of computer-assisted morphometry, Vascular density was assessed by immunohistochemical stain for VEGF and factor VIII, Results: Compared with group III, increased angiogenic factor levels were found in group I (VEGF 0.47 +/- 0.03 mm(2) vs 0.05 +/- 0.05 mm(2), P = .000; bFGF 0.67 +/- 0.14 mm2 vs 0.03 +/- 0.03 mm(2), P = .000; TGF-beta 1.40 +/- 0.18 mm2 vs 0.09 +/- 0.06 mm(2), P = 0.000), and in group II (VEGF 0.34 +/- 0.06 mm(2) vs 0.05 +/- 0.05 mm(2), P = .003; bFGF 0.06 +/- 0.02 mm(2) vs 0.03 +/- 0.03 mm(2), P = .135; TGF-beta 0.28 +/- 0.09 mm(2) vs 0.09 +/- 0.06 mm(2), P = .042), Vascular densities after mechanical transmyocardial revascularization were also increased (group I, VEGF stain 8.1 +/- 0.6 vs 1.1 +/- 0.5, P = .000; factor VIII stain 5.1 +/- 2.7 vs 0.4 +/- 0.3, P = .018; group II, VEGF stain 1.9 +/- 0.5 vs 1.1 +/- 0.5, P = 0.107; factor VIII stain 2.3 +/- 0.4 vs 0.4 +/- 0.3, P = .004), Conclusions: Mechanical transmyocardial revascularization is associated with increased angiogenic factor expression and concomitant neovascularization at up to 4 weeks. These changes are indistinguishable from those of laser transmyocardial revascularization. Myocardial perfusion studies are needed to establish the functional significance of these angiogenic changes.