期刊
CIRCULATION
卷 104, 期 20, 页码 2407-2411出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hc4501.098928
关键词
heart failure; hemodynamics; free radicals
资金
- NHLBI NIH HHS [R01 HL-65455, K08 HL-03238] Funding Source: Medline
Background-Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption. Experimental models suggest that oxidative stress resulting from increased xanthine oxidase (XO) activity contributes to this imbalance. Accordingly, we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy. Methods and Results-Patients (n=9; ejection fraction, 29 +/-3%) were instrumented to assess myocardial oxygen consumption (M(V) over doto(2)), peak rate of rise of left ventricular pressure (dP/dt(max)), stroke work (SW), and efficiency (dP/dt(max)/M(V) over doto(2) and SW/M(V) over doto(2)) at baseline and after sequential infusions of intracoronary allopurinol (0.5, 1.0, and 1.5 mg/min, each for 15 minutes). Allopurinol caused a significant decrease in M(V) over doto(2) (peak effect, -16 +/-5%; P <0.01; n=9) with no parallel decrease in dP/dt(max) or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dt(max)/M(V) over doto(2), 22 +/-9%, n=9; SW/M(V) over doto(2), 40 +/- 17%, n=6; both P <0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and beta -blockers. XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot. Conclusions-These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy. By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据