Abstract 14794: A Slow-Release Synthetic Prostacyclin Agonist “YS1402” Combined With Pedicle Omental Flap Reduces Microvascular Resistance and Increases Myocardial Blood Flow, Associated With Functional Recovery, in a Porcine Chronic Myocardial Infarction Model
Introduction: YS1402 is a slow-release synthetic prostacyclin agonist, being developed as multi-proangiogenic cytokines inducer. In addition, the pedicle omental flap covering over the left ventricle (LV) reportedly yields proangiogenic effects on myocardial infarction (MI).
Hypothesis: We hypothesized therapeutic efficacy may be augmented by combination of YS1402 placement over the LV with the pedicle omental flap in a chronic MI heart.
Methods: A mini-pig chronic MI was generated by placing an ameroid constrictor ring around the left anterior descending artery for 4 weeks. They were then assigned into the 4 groups; sham, omental flap only (OM), YS1402 only (YS), omental flap and YS1402 (Combined, n=8 each).
Results: In angiogram and pressure wire study at 4 weeks after the therapy, the YS and the Combined groups displayed a significantly greater number of collateral arteries and a smaller index of microvascular resistance, in particular, in the left circumflex (LCX) area, compared to the other groups. Moreover, temporary occlusion of the LCX induced increase of blood flow in the gastroepiploic artery (GEA) of the Combined group (1.2±0.2 fold), but not of the OM group (0.7±0.1 fold, P <0.05). In 13N-ammonia PET study, the Combined group, but not the other groups, displayed a significant increase in myocardial blood flow (1.9±0.9 fold, P <0.05) and coronary flow reserve (1.8±1.2% fold, P <0.05) under the stress compared to those under the rest. In addition, ejection fraction was significantly greater in the Combined (50±3%) and the YS (51±2%) groups than the OM (42±2%) and the sham (40±2%) groups. Moreover, vascular connection between the GEA and the heart was histologically identified in the Combined group, but not in the OM group. The density of CD31-positive capillaries and CD31/SMA-double positive arterioles were significantly greater in Combined group than the sham or the OM groups. The expression of vascular endothelial growth factor and basic fibroblast growth factor in the infarct border myocardium were significantly higher in the Combined and the YS groups than that in the sham group.
Conclusions: YS1402 combined with omental flap therapy synergistically promoted myocardial angiogenesis, leading to functional recovery in a porcine chronic MI model.
Author Disclosures: S. Yajima: None. S. Miyagawa: None. S. Fukushima: None. Y. Sakai: None. A. Harada: None. H. Iseoka: None. M. Shiozaki: None. T. Watabe: None. K. Isohashi: None. H. Ikeda: None. G. Horitsugi: None. J. Hatazawa: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.