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

Genya Sunagawa, Keita Saku, Takahiro Arimura, Takuya Nishikawa, Hiroshi Mannoji, Kazuhiro Kamada, Kiyokazu Abe, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)124-134
Number of pages11
JournalJournal of Cardiovascular Translational Research
Volume12
Issue number2
DOIs
Publication statusPublished - Apr 15 2019

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ivabradine
Oxygen Consumption
Myocardial Infarction
Ischemia
Reperfusion
Heart Rate
Dogs
Oxygen
Control Groups

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Mechano-chronotropic Unloading During the Acute Phase of Myocardial Infarction Markedly Reduces Infarct Size via the Suppression of Myocardial Oxygen Consumption. / Sunagawa, Genya; Saku, Keita; Arimura, Takahiro; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Abe, Kiyokazu; Kishi, Takuya; Tsutsui, Hiroyuki; Sunagawa, Kenji.

In: Journal of Cardiovascular Translational Research, Vol. 12, No. 2, 15.04.2019, p. 124-134.

Research output: Contribution to journalArticle

Sunagawa, Genya ; Saku, Keita ; Arimura, Takahiro ; Nishikawa, Takuya ; Mannoji, Hiroshi ; Kamada, Kazuhiro ; Abe, Kiyokazu ; Kishi, Takuya ; Tsutsui, Hiroyuki ; Sunagawa, Kenji. / Mechano-chronotropic Unloading During the Acute Phase of Myocardial Infarction Markedly Reduces Infarct Size via the Suppression of Myocardial Oxygen Consumption. In: Journal of Cardiovascular Translational Research. 2019 ; Vol. 12, No. 2. pp. 124-134.
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abstract = "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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