Probucol attenuates left ventricular dysfunction and remodeling in tachycardia-induced heart failure: Roles of oxidative stress and inflammation

Ryo Nakamura, Kensuke Egashira, Youji Machida, Shunji Hayashidani, Motohiro Takeya, Hideo Utsumi, Hiroyuki Tsutsui, Akira Takeshita

研究成果: ジャーナルへの寄稿学術誌査読

110 被引用数 (Scopus)

抄録

Background - Oxidative stress and inflammation are potentially involved in the pathogenesis of heart failure (HF). We examined whether antioxidant and antiinflammatory treatment with probucol decreases myocardial oxidative stress and inflammation and attenuates the progression of left ventricular (LV) dysfunction and remodeling (dilatation) in tachycardia-induced HF. Methods and Results - We studied 3 groups of dogs: a sham-operated control group and 2 other groups that underwent ventricular pacing at 240 bpm with and without probucol treatment (100 mg/kg IP per week) for 4 weeks. Dogs that underwent ventricular pacing for 4 weeks developed signs of HF, such as a reduction in the LV ejection fraction and increases in the LV end-diastolic dimension and LV end-diastolic pressure. Myocardial oxidative stress, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6,-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO), was significantly increased. There was an increase in myocardial monocyte infiltration, monocyte chemoattractant protein- 1 expression, and renin-angiotensin system and matrix metalloproteinase activity. Probucol treatment prevented increases in oxidative stress, inflammation, and matrix metalloproteinase activity and attenuated LV dysfunction and remodeling. Conclusions - Probucol attenuated LV dysfunction and remodeling, possibly through its antioxidant and/or antiinflammatory effects in ventricular pacing-induced HF. These data suggest that inflammatory disorders, which cause an abnormal interaction between failing myocardium and activated monocytes, have an important role in the progression of HF.

本文言語英語
ページ(範囲)362-367
ページ数6
ジャーナルCirculation
106
3
DOI
出版ステータス出版済み - 7月 16 2002

!!!All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学
  • 生理学(医学)

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