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We tested the hypothesis that TMLR combined with intramyocardial injection of BMC is safe, and may help increase the functional capacity of patient with refractory angina.Nine patients (eight men), 65+/-5 years old, with refractory angina for multivessel disease and previous myocardial revascularization procedures (CABG/PCI), not candidates for another procedure due to the extension of the disease were enrolled. TMLR (11+/-3 laser drills) was performed via a limited thoracotomy using a CO2 Heart Laser System. BMC were obtained immediately prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing approximately 1.9+/-0.3 x 10(8) BMC were delivered by multiple injections in the ischemic myocardium. Before (B) and 6 months (6M) after the procedure, patient underwent clinical evaluation and myocardial perfusion assessment by cardiac magnetic resonance imaging (MRI) during pharmacological stress with dypiridamole.No major complications or deaths occurred during the procedure. One patient died after 2 years (non cardiac cause). There was a reduction in the ischemic score as assessed by MRI from 1.64+/-0.10 (B) to 0.88+/-0.09 (6M) (P=0.01). Clinically, there was a reduction in functional class of angina from 3.7+/-0.2 (B) to 1.3+/-0.2 (6M) (P0.0001).In this initial experience, the combined strategy of TMLR plus cell therapy appeared to be safe, and may have synergistically acted to reduce myocardial ischemia, with clinically relevant improvement in functional capacity. Provided these data are confirmed in a larger, randomized, controlled trial with longer follow-up, this strategy could be used as a novel therapeutic option for treating pt with refractory angina.