TY - JOUR
T1 - Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function
AU - Atluri, Pavan
AU - Panlilio, Corinna M.
AU - Liao, George P.
AU - Suarez, Eric E.
AU - McCormick, Ryan C.
AU - Hiesinger, William
AU - Cohen, Jeffrey E.
AU - Smith, Maximilian J.
AU - Patel, Abha B.
AU - Feng, Wei
AU - Woo, Y. Joseph
N1 - Funding Information:
Supported in part by grants from the National Institutes of Health National Heart Lung and Blood Institute/Thoracic Surgery Foundation for Research and Education (HL072812, YJW), unrestricted investigational grant from Cardiogenesis Corporation (YJW), and National Institutes of Health, National Heart Lung Blood Institute—Ruth L. Kirschstein National Research Service Award (Individual Fellowship 1 F32 HL79769-01, PA).
PY - 2008/2
Y1 - 2008/2
N2 - Objective: A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization. Methods: Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis. Results: Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor κB (42 ± 27 intensity units vs 591 ± 383 intensity units, P = .03) and angiopoietin 1 (0 ± 0 intensity units vs 241 ± 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 ± 8.7 vessels/high-power field vs 31.4 ± 10.2 vessels/high-power field, P = .02), and perfusion (0.028 ± 0.009 μm3 blood/μm3 tissue vs 0.044 ± 0.004 μm3 blood/μm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 ± 8.5 cardiomyocytes/high-power field vs 50.8 ± 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 ± 0.2 L/min vs 2.7 ± 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% ± 3.6% vs 76.1% ± 3.4%, P = .008). Conclusion: Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.
AB - Objective: A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization. Methods: Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis. Results: Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor κB (42 ± 27 intensity units vs 591 ± 383 intensity units, P = .03) and angiopoietin 1 (0 ± 0 intensity units vs 241 ± 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 ± 8.7 vessels/high-power field vs 31.4 ± 10.2 vessels/high-power field, P = .02), and perfusion (0.028 ± 0.009 μm3 blood/μm3 tissue vs 0.044 ± 0.004 μm3 blood/μm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 ± 8.5 cardiomyocytes/high-power field vs 50.8 ± 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 ± 0.2 L/min vs 2.7 ± 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% ± 3.6% vs 76.1% ± 3.4%, P = .008). Conclusion: Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.
UR - http://www.scopus.com/inward/record.url?scp=38649090073&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2007.09.043
DO - 10.1016/j.jtcvs.2007.09.043
M3 - Article
C2 - 18242252
AN - SCOPUS:38649090073
SN - 0022-5223
VL - 135
SP - 283-291.e1
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 2
ER -