A clinically relevant large-animal model for evaluation of tissue-engineered cardiac surgical patch materials

Abstract

Extracellular matrix (ECM) scaffolds may be useful as a tissue engineering approach toward myocardial regeneration in the infarcted heart. An appropriate large-animal model for testing the utility of biologically derived ECM in this application is needed. The purpose of this study was to develop such a model for optimal procedural success during and after patch implantation surgery. Myocardial infarction (MI) was created by embolization of the diagonal artery (DA) branch of the left anterior descending coronary artery with collagen suspension. After 4 to 6 weeks, 14 pigs received patch implant (ECM or expanded polytetrafluoroethylene). Six pigs were infarcted in the first DA and seven pigs in the second DA. Electrophysiology study was performed within 3 days before surgery. During surgery, the size and location of the infarct were measured. Infarcted myocardium (1.5-cm diameter) was transmurally excised under partial cardiopulmonary bypass. Patches (3-cm diameter) were sutured to the endomyocardial defect. Four pigs died postoperatively. After 1 month, 10 pigs were euthanized and the locations of patches were examined. Success rate of patch implant in the second DA (85.7%) was higher than the first DA (50%) group. Infarct size in the second DA was smaller than in the first DA (4.6+/-1.2 vs. 10.8+/-2.4 cm(2), P<.05). The second DA was more anteriorly positioned, which enabled easier access from the midsternal thoracotomy. However, the first DA was more laterally located requiring more manipulation of the heart during surgery. Electrophysiology revealed no ventricular tachyarrhythmia in the second DA but 33.3% in the first DA group (P<.05). At necropsy, the endocardial position of the first DA-infarct patches was anteroapical, whereas the second DA-infarct patches were more basolateral and often involved the anterior papillary muscle. The success rate of patch implant was associated with infarction size and location, and may be related to arrhythmic substrate. Experimental MI created by the second DA embolization is a feasible model for investigation of tissue-engineered cardiac patch implantation. This large-animal model is also suitable for study of cell therapy via endocardial catheter-based approaches or open surgical methods.