OBJECTIVE: We hypothesized that therapeutic efficacy may be augmented by a combination of placing a sheet immersed in ONO-1301SR, a slow-release synthetic prostacyclin agonist-inducing multiproangiogenic cytokines, over the left ventricle and a pedicled omental flap in a chronic myocardial infarct heart. METHODS: A minipig chronic myocardial infarction was generated by placing an ameroid constrictor ring around the left anterior descending artery for 4 weeks. The minipigs were then assigned into 4 groups of 6 each: sham, omental flap only, ONO-1301SR only, and ONO-1301SR combined with an omental flap (combined). Four weeks after treatment, therapeutic efficacy was evaluated histologically and via several modalities used in the clinical setting. RESULTS: In an angiogram and pressure wire study, the combined group induced development of collateral arteries to decrease the resistance and increase the flow reserve of microvasculature in the left circumflex territory. In a 13N-ammonia positron emission tomography study, the combined group displayed a prominent increase in myocardial blood flow and myocardial flow reserve in the left circumflex territory, particularly at the infarct-border region. Consequently, the combined group showed greater regional cardiac function in the left circumflex territory particularly at the infarct-border region, contributing to a greater global ejection fraction with a smaller left ventricular endosystolic volume. Pathologically, attenuated fibrosis, nonswollen myocytes, and upgraded capillary density and proangiogenic cytokines were prominent in the combined group. CONCLUSIONS: ONO-1301SR combined with a pedicled omental flap synergistically promoted myocardial angiogenesis, leading to function recovery in a porcine chronic myocardial infarction model.
OBJECTIVE: We hypothesized that therapeutic efficacy may be augmented by a combination of placing a sheet immersed in ONO-1301SR, a slow-release synthetic prostacyclin agonist-inducing multiproangiogenic cytokines, over the left ventricle and a pedicled omental flap in a chronic myocardial infarct heart. METHODS: A minipig chronic myocardial infarction was generated by placing an ameroid constrictor ring around the left anterior descending artery for 4 weeks. The minipigs were then assigned into 4 groups of 6 each: sham, omental flap only, ONO-1301SR only, and ONO-1301SR combined with an omental flap (combined). Four weeks after treatment, therapeutic efficacy was evaluated histologically and via several modalities used in the clinical setting. RESULTS: In an angiogram and pressure wire study, the combined group induced development of collateral arteries to decrease the resistance and increase the flow reserve of microvasculature in the left circumflex territory. In a 13N-ammonia positron emission tomography study, the combined group displayed a prominent increase in myocardial blood flow and myocardial flow reserve in the left circumflex territory, particularly at the infarct-border region. Consequently, the combined group showed greater regional cardiac function in the left circumflex territory particularly at the infarct-border region, contributing to a greater global ejection fraction with a smaller left ventricular endosystolic volume. Pathologically, attenuated fibrosis, nonswollen myocytes, and upgraded capillary density and proangiogenic cytokines were prominent in the combined group. CONCLUSIONS: ONO-1301SR combined with a pedicled omental flap synergistically promoted myocardial angiogenesis, leading to function recovery in a porcine chronic myocardial infarction model.