Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo

Xiao Shu Cheng, Hiroaki Shimokawa, Hidetoshi Momii, Jun Ichi Oyama, Naoto Fukuyama, Kensuke Egashira, Hiroe Nakazawa, Akira Takeshita

研究成果: ジャーナルへの寄稿記事

38 引用 (Scopus)

抄録

Objective: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. Methods: Studies were performed in mongrel dogs, in which microspheres (MS, 15 μm in diameter) with and without interleukin-1β (IL-1β) were injected into the left main coronary artery (control and IL-1β group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. Results: Immediately after the intracoronary injection of MS (106/kg), LVEF equally decreased to approximately 30% in both the control and IL-1β group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1β group until day 7 (p<0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg IV) and 1 and 2 days after IL-1β MS application (1 mg/kg IV) prevented the IL-1β-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1β group than in the control group at day 2 (p<0.01), and OPC-6535 significantly suppressed the IL-1β-induced superoxide production (p<0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1β but not in that with control MS. OPC-6535 abolished the IL-1β-induced formation of myocardial nitrotyrosine. Conclusion: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.

元の言語英語
ページ(範囲)651-659
ページ数9
ジャーナルCardiovascular research
42
発行部数3
DOI
出版物ステータス出版済み - 6 1 1999

Fingerprint

Interleukin-1
Superoxides
Dogs
Cytokines
Stroke Volume
Peroxynitrous Acid
Control Groups
Myocardium
Microspheres
Free Radicals
Echocardiography
Canidae
Coronary Vessels
Nitric Oxide
High Pressure Liquid Chromatography
Oxygen
Injections
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

これを引用

Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo. / Cheng, Xiao Shu; Shimokawa, Hiroaki; Momii, Hidetoshi; Oyama, Jun Ichi; Fukuyama, Naoto; Egashira, Kensuke; Nakazawa, Hiroe; Takeshita, Akira.

:: Cardiovascular research, 巻 42, 番号 3, 01.06.1999, p. 651-659.

研究成果: ジャーナルへの寄稿記事

Cheng, XS, Shimokawa, H, Momii, H, Oyama, JI, Fukuyama, N, Egashira, K, Nakazawa, H & Takeshita, A 1999, 'Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo', Cardiovascular research, 巻. 42, 番号 3, pp. 651-659. https://doi.org/10.1016/S0008-6363(98)00317-4
Cheng, Xiao Shu ; Shimokawa, Hiroaki ; Momii, Hidetoshi ; Oyama, Jun Ichi ; Fukuyama, Naoto ; Egashira, Kensuke ; Nakazawa, Hiroe ; Takeshita, Akira. / Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo. :: Cardiovascular research. 1999 ; 巻 42, 番号 3. pp. 651-659.
@article{c30cc41d43184c0e8ca75f11d1ba1b79,
title = "Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo",
abstract = "Objective: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. Methods: Studies were performed in mongrel dogs, in which microspheres (MS, 15 μm in diameter) with and without interleukin-1β (IL-1β) were injected into the left main coronary artery (control and IL-1β group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. Results: Immediately after the intracoronary injection of MS (106/kg), LVEF equally decreased to approximately 30{\%} in both the control and IL-1β group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1β group until day 7 (p<0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg IV) and 1 and 2 days after IL-1β MS application (1 mg/kg IV) prevented the IL-1β-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1β group than in the control group at day 2 (p<0.01), and OPC-6535 significantly suppressed the IL-1β-induced superoxide production (p<0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1β but not in that with control MS. OPC-6535 abolished the IL-1β-induced formation of myocardial nitrotyrosine. Conclusion: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.",
author = "Cheng, {Xiao Shu} and Hiroaki Shimokawa and Hidetoshi Momii and Oyama, {Jun Ichi} and Naoto Fukuyama and Kensuke Egashira and Hiroe Nakazawa and Akira Takeshita",
year = "1999",
month = "6",
day = "1",
doi = "10.1016/S0008-6363(98)00317-4",
language = "English",
volume = "42",
pages = "651--659",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo

AU - Cheng, Xiao Shu

AU - Shimokawa, Hiroaki

AU - Momii, Hidetoshi

AU - Oyama, Jun Ichi

AU - Fukuyama, Naoto

AU - Egashira, Kensuke

AU - Nakazawa, Hiroe

AU - Takeshita, Akira

PY - 1999/6/1

Y1 - 1999/6/1

N2 - Objective: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. Methods: Studies were performed in mongrel dogs, in which microspheres (MS, 15 μm in diameter) with and without interleukin-1β (IL-1β) were injected into the left main coronary artery (control and IL-1β group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. Results: Immediately after the intracoronary injection of MS (106/kg), LVEF equally decreased to approximately 30% in both the control and IL-1β group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1β group until day 7 (p<0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg IV) and 1 and 2 days after IL-1β MS application (1 mg/kg IV) prevented the IL-1β-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1β group than in the control group at day 2 (p<0.01), and OPC-6535 significantly suppressed the IL-1β-induced superoxide production (p<0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1β but not in that with control MS. OPC-6535 abolished the IL-1β-induced formation of myocardial nitrotyrosine. Conclusion: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.

AB - Objective: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. Methods: Studies were performed in mongrel dogs, in which microspheres (MS, 15 μm in diameter) with and without interleukin-1β (IL-1β) were injected into the left main coronary artery (control and IL-1β group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. Results: Immediately after the intracoronary injection of MS (106/kg), LVEF equally decreased to approximately 30% in both the control and IL-1β group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1β group until day 7 (p<0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg IV) and 1 and 2 days after IL-1β MS application (1 mg/kg IV) prevented the IL-1β-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1β group than in the control group at day 2 (p<0.01), and OPC-6535 significantly suppressed the IL-1β-induced superoxide production (p<0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1β but not in that with control MS. OPC-6535 abolished the IL-1β-induced formation of myocardial nitrotyrosine. Conclusion: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0032997657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032997657&partnerID=8YFLogxK

U2 - 10.1016/S0008-6363(98)00317-4

DO - 10.1016/S0008-6363(98)00317-4

M3 - Article

C2 - 10533605

AN - SCOPUS:0032997657

VL - 42

SP - 651

EP - 659

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -