TY - JOUR
T1 - Mechano-chronotropic Unloading During the Acute Phase of Myocardial Infarction Markedly Reduces Infarct Size via the Suppression of Myocardial Oxygen Consumption
AU - Sunagawa, Genya
AU - Saku, Keita
AU - Arimura, Takahiro
AU - Nishikawa, Takuya
AU - Mannoji, Hiroshi
AU - Kamada, Kazuhiro
AU - Abe, Kiyokazu
AU - Kishi, Takuya
AU - Tsutsui, Hiroyuki
AU - Sunagawa, Kenji
N1 - Funding Information:
Conflict of Interest K. Sunagawa works in a department endowed by Omron Healthcare Co. and Actelion Pharmaceuticals, Japan, and has received research resources (Impella console and Impella CP® catheters) from Abiomed Inc. K. Saku and T. Kishi work in a department endowed by Omron Healthcare Co. G. Sunagawa, T. Arimura, T. Nishikawa, H. Mannoji, K. Kamada, and K. Abe have nothing to declare. H. Tsutsui received honoraria from Daiichi Sankyo, Inc., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Mitsubishi Tanabe Pharma Corporation, Boehringer Ingelheim Japan, Inc., Novartis Pharma K.K., Bayer Yakuhin, Ltd., Bristol-Myers Squibb KK, and Astellas Pharma Inc. and research funding from Actelion Pharmaceuticals Japan, Daiichi Sankyo, Inc. and Astellas Pharma Inc.
Funding Information:
Sources of Funding This work was supported by research and development of supportive device technology for medicine using ICT from Japan Agency for Medical Research and Development of Advanced Measurement and Analysis Systems from Japan Agency for Medical Research and Development.
Funding Information:
The authors thank Takuya Akashi, Takako Takehara, and the staff of the Center for Disruptive Cardiovascular Medicine, Kyushu University, and the Department of Cardiovascular Medicine, Kyushu University, for the technical support. This work was supported by research and development of supportive device technology for medicine using ICT from Japan Agency for Medical Research and Development of Advanced Measurement and Analysis Systems from Japan Agency for Medical Research and Development.
Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/4/15
Y1 - 2019/4/15
N2 - The oxygen supply-demand imbalance is the fundamental pathophysiology of myocardial infarction (MI). Reducing myocardial oxygen consumption (MVO 2 ) in acute MI (AMI) reduces infarct size. Since left ventricular (LV) mechanical work and heart rate are major determinants of MVO 2 , we hypothesized that the combination of LV mechanical unloading and chronotropic unloading during AMI can reduce infarct size via synergistic suppression of MVO 2 . In a dog model of ischemia-reperfusion, as we predicted, the combination of mechanical unloading by Impella and bradycardic agent, ivabradine (IVA), synergistically reduced MVO 2 . This was translated into the striking reduction of infarct size with Impella + IVA administered 60 min after the onset of ischemia compared to no treatment (control) and Impella groups (control 56.3 ± 6.5, Impella 39.9 ± 7.4 and Impella + IVA 23.7 ± 10.6%, p < 0.001). In conclusion, Impella + IVA during AMI reduced infarct size via marked suppression of MVO 2 . The mechano-chronotropic unloading may serve as a powerful therapeutic option for AMI.
AB - The oxygen supply-demand imbalance is the fundamental pathophysiology of myocardial infarction (MI). Reducing myocardial oxygen consumption (MVO 2 ) in acute MI (AMI) reduces infarct size. Since left ventricular (LV) mechanical work and heart rate are major determinants of MVO 2 , we hypothesized that the combination of LV mechanical unloading and chronotropic unloading during AMI can reduce infarct size via synergistic suppression of MVO 2 . In a dog model of ischemia-reperfusion, as we predicted, the combination of mechanical unloading by Impella and bradycardic agent, ivabradine (IVA), synergistically reduced MVO 2 . This was translated into the striking reduction of infarct size with Impella + IVA administered 60 min after the onset of ischemia compared to no treatment (control) and Impella groups (control 56.3 ± 6.5, Impella 39.9 ± 7.4 and Impella + IVA 23.7 ± 10.6%, p < 0.001). In conclusion, Impella + IVA during AMI reduced infarct size via marked suppression of MVO 2 . The mechano-chronotropic unloading may serve as a powerful therapeutic option for AMI.
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U2 - 10.1007/s12265-018-9809-x
DO - 10.1007/s12265-018-9809-x
M3 - Article
C2 - 29736746
AN - SCOPUS:85046545485
SN - 1937-5387
VL - 12
SP - 124
EP - 134
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 2
ER -