Probucol attenuates left ventricular dysfunction and remodeling in tachycardia-induced heart failure - Roles of oxidative stress and inflammation
Probucol attenuates left ventricular dysfunction and remodeling in tachycardia-induced heart failure - Roles of oxidative stress and inflammation
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DOI：
10.1161/01.cir.0000021430.04195.51
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发表时间：
2002-07-16
期刊：
影响因子：
37.8
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Nakamura, R;Egashira, K;Takeshita, A
背景-氧化应激和炎症可能参与心力衰竭（HF）的发病机制。我们研究了抗氧化剂和抗氧化剂联合普罗布考治疗是否能降低心肌氧化应激和炎症，并减缓左心室功能障碍和重塑的进展方法和结果-我们研究了3组狗：一个假手术对照组和另外两个接受240 bpm心室起搏并有和没有普罗布考治疗的组（100 mg/kg IP/周）持续4周。接受心室起搏4周的犬出现HF体征，如LV射血分数降低，LV舒张末期尺寸和LV舒张末期压增加。用4-羟基-2，2，6，6-四甲基-哌啶-N-氧基（羟基-TEMPO）通过电子自旋共振光谱测量的心肌氧化应激显著增加。心肌单核细胞浸润、单核细胞趋化蛋白-1表达、肾素-血管紧张素系统和基质金属蛋白酶活性增加。普罗布考治疗预防氧化应激，炎症，基质金属蛋白酶活性和衰减LV功能障碍和remodel. Conclusions普罗布考衰减LV功能障碍和重塑，可能通过其抗氧化剂和/或抗氧化剂的作用，在心室起搏诱导HF的增加。这些数据表明，炎症性疾病，这会导致一个异常的相互作用之间的失败的心肌和激活的单核细胞，有一个重要的作用，在HF的进展。
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.