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Mechano-chronotropic Unloading During the Acute Phase of Myocardial Infarction Markedly Reduces Infarct Size via the Suppression of Myocardial Oxygen Consumption

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Abstract

The oxygen supply-demand imbalance is the fundamental pathophysiology of myocardial infarction (MI). Reducing myocardial oxygen consumption (MVO2) in acute MI (AMI) reduces infarct size. Since left ventricular (LV) mechanical work and heart rate are major determinants of MVO2, we hypothesized that the combination of LV mechanical unloading and chronotropic unloading during AMI can reduce infarct size via synergistic suppression of MVO2. In a dog model of ischemia-reperfusion, as we predicted, the combination of mechanical unloading by Impella and bradycardic agent, ivabradine (IVA), synergistically reduced MVO2. 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 MVO2. The mechano-chronotropic unloading may serve as a powerful therapeutic option for AMI.

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Abbreviations

AMI:

Acute myocardial infarction

AP:

Arterial pressure

CS:

Coronary sinus

EDPVR:

End-diastolic pressure-volume relationship

EDV:

End-diastolic volume

ESPVR:

End-systolic pressure-volume relationship

ESV:

End-systolic volume

HR:

Heart rate

IVA:

Ivabradine

LAD:

Left anterior descending coronary artery

LCX:

Left circumflex coronary artery

LAP:

Left atrial pressure

LV:

Left ventricle or left ventricular

LVAD:

Left ventricular assist device

LVP:

Left ventricular pressure

LVV:

Left ventricular volume

MAP:

Mean arterial pressure

MI:

Myocardial infarction

MVO2 :

Myocardial oxygen consumption

PCI:

Percutaneous coronary intervention

PV:

Pressure-volume

PVA:

Pressure-volume area

RAP:

Right atrial pressure

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Acknowledgments

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.

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.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Genya Sunagawa, Takahiro Arimura, Takuya Nishikawa, Hiroshi Mannoji, Kazuhiro Kamada & Hiroyuki Tsutsui

  2. Department of Advanced Risk Stratification for Cardiovascular Diseases, Center for Disruptive Cardiovascular Medicine, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Keita Saku & Takuya Kishi

  3. Department of Anesthesiology & Critical Care Medicine, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Kiyokazu Abe

  4. Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Kenji Sunagawa

Authors
  1. Genya Sunagawa
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Corresponding author

Correspondence to Keita Saku.

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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.

Human Subjects/Informed Consent Statement

No human studies were carried out by the authors for this article.

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Associate Editor Navin Kumar Kapur oversaw the review of this article.

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Sunagawa, G., Saku, K., Arimura, T. et al. Mechano-chronotropic Unloading During the Acute Phase of Myocardial Infarction Markedly Reduces Infarct Size via the Suppression of Myocardial Oxygen Consumption. J. of Cardiovasc. Trans. Res. 12, 124–134 (2019). https://doi.org/10.1007/s12265-018-9809-x

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