Pavan Atluri, Erik E. Suarez, George P. Liao, Corinna Panlilio, John B. Hye, William Hiesinger, Jeffrey E. Cohen, Maximillian J. Smith, Rebecca Levitt, Y. Joseph Woo; Division of Cardiothoracic Surgery, University of Pennsylvania, Philadelphia, PA
Objective: A large number of patients have coronary artery disease without completely revascularizable anatomy. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial revascularization (TMR) in this cohort. However, the molecular mechanisms underlying this therapy are poorly understood. This study focused on evaluating the purported vasculogenic mechanisms involved in therapeutic transmyocardial revascularization.
Methods: Male, Yorkshire pigs (n=16) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. Over a 4 week period the animals developed a well defined region of myocardial ischemia and underwent a redo left thoracotomy. The animals were randomized to either sham thoracotomy as control (n=8) or TMR of the ischemic myocardium with a holmium-YAG laser (n=8). After an additional 4 weeks the animals underwent median sternotomy and echocardiographic analysis of wall motion, as well as hemodynamic analysis utilizing an ascending aortic flow probe and pulmonary artery catheter. The hearts were then explanted for analysis of angiogenesis utilizing CD31 immunofluorescent labeling and myocardial viability with myofilament density quantification.
Results: Molecular analysis demonstrated a statistically significant increase in angiogenesis within the ischemic myocardium with TMR therapy as compared to sham control. Enhanced myocardial viability was demonstrated by increased myofilament density. Regional myocardial function within the treated region demonstrated augmented contractility. Global hemodynamic function was significantly improved with TMR therapy as compared to control. There was no difference in heart rate, preload, afterload, or hemoglobin between the two groups. [Table]
Conclusion: Transmyocardial revascularization enhances myocardial vasculogenesis and augments cardiac function in myocardial ischemia.
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