Acute effects of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in pacing induced heart failure
Acute effects of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in pacing induced heart failure
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DOI：
10.1097/01.fjc.0000249961.61451.da
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发表时间：
2006-11-01
影响因子：
3
通讯作者：
Bache, Robert J.
中科院分区：
文献类型：
--
作者：
Hou, Mingxiao;Hu, Qingsong;Bache, Robert J.
我们研究了非布司他抑制黄嘌呤氧化酶是否能增强起搏性心力衰竭（CHF）犬的左心室（LV）功能并改善心肌高能量磷酸盐（HEP）。非布司他（2.2 mg/kg/ 10min后再加0.06 mg/kg/min）对正常犬静息或在跑步机上运动时左室功能和心肌耗氧量（MVO2）没有影响。在CHF犬中，非布司他在静止和剧烈运动时增加了左室dP/dt(max) (P < 0.05)，表明左室功能得到改善，但MVO2没有变化。应用P-31核磁共振波谱法检测开胸状态心肌三磷酸腺苷（ATP）和磷酸肌酸（PCr）。在正常犬的基础状态和多巴酚丁胺+多巴胺产生的高负荷时，非布司他增加了PCr/ATP （P < 0.05）。CHF动物的PCr/ATP降低；在这些动物中，非布司他（在用载具完成基础和高负荷测量后给予）倾向于在基础条件下增加PCr/ATP，而在儿茶酚胺刺激时没有影响。因此，非布司他改善了醒着的CHF犬的静脉注射表现，但只导致开胸状态下PCr/ATP增加的趋势。这可能是药物给药前的高负荷条件减弱了非布司他对CHF动物HER的影响。另外，非布司他对衰竭心脏静脉功能的有益影响可能与HEP无关。
We investigated whether xanthine oxidase inhibition with febuxostat enhances left ventricular (LV) function and improves myocardial high energy phosphates (HEP) in dogs with pacing-induced heart failure (CHF). Febuxostat (2.2 mg/kg over 10 minutes followed by 0.06 mg/kg/min) caused no change of LV function or myocardial oxygen consumption (MVO2) at rest or during treadmill exercise in normal dogs. In dogs with CHF, febuxostat increased LV dP/dt(max) at rest and during heavy exercise (P < 0.05), indicating improved LV function with no change of MVO2. Myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) were examined using P-31 nuclear magnetic resonance spectroscopy in the open chest state. In normal dogs, febuxostat increased PCr/ATP during basal conditions and during high workload produced by dobutamine + dopamine (P < 0.05). PCr/ATP was decreased in animals with CHF; in these animals, febuxostat (given after completing basal and high workload measurements with vehicle) tended to increase PCr/ATP during basal conditions with no effect during catecholamine stimulation. Thus, febuxostat improved IV performance in awake dogs with CHF, but caused only a trend toward increased PCr/ATP in the open chest state. It is possible that the antecedent high workload condition prior to drug administration blunted the effect of febuxostat on HER in the CHF animals. Alternatively, beneficial effects of febuxostat on IV performance in the failing heart may not involve HEP.