TY - JOUR
T1 - A prostacyclin agonist and an omental flap increased myocardial blood flow in a porcine chronic ischemia model
AU - Yajima, Shin
AU - Miyagawa, Shigeru
AU - Fukushima, Satsuki
AU - Sakai, Yoshiki
AU - Isohashi, Kayako
AU - Watabe, Tadashi
AU - Ikeda, Hayato
AU - Horitsugi, Genki
AU - Harada, Akima
AU - Sakaniwa, Ryoto
AU - Hatazawa, Jun
AU - Sawa, Yoshiki
N1 - Publisher Copyright:
© 2018 The American Association for Thoracic Surgery
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - ONO-1301
KW - microvascular dysfunction
KW - myocardial blood flow
KW - omental flap
KW - prostacyclin
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U2 - 10.1016/j.jtcvs.2018.02.086
DO - 10.1016/j.jtcvs.2018.02.086
M3 - Article
C2 - 29627179
AN - SCOPUS:85044866024
VL - 156
SP - 229-241.e14
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
SN - 0022-5223
IS - 1
ER -