慢性心力衰竭中选择性与非选择性β-肾上腺素能受体阻滞剂：对心肌能量底物利用的不同影响

Selective versus nonselective beta-adrenergic receptor blockade in chronic heart failure: differential effects on myocardial energy substrate utilization.

作者信息

Al-Hesayen Abdul, Azevedo Eduardo R, Floras John S, Hollingshead Shauna, Lopaschuk Gary D, Parker John D

机构信息

Division of Cardiology, Department of Medicine, Mount Sinai Hospital and University Health Network Hospitals, University of Toronto, 600 University Avenue, Suite 1609, Toronto, Ontario, Canada, M5G 1X5.

出版信息

Eur J Heart Fail. 2005 Jun;7(4):618-23. doi: 10.1016/j.ejheart.2004.04.015.

DOI:10.1016/j.ejheart.2004.04.015

PMID:15921803

Abstract

BACKGROUND

Non-selective and selective beta-blockers have been shown to improve outcomes in chronic heart failure (CHF). Recent data suggests the non-selective beta-blockers have a more favourable effect on outcomes than beta(1)-selective agents. We sought to examine the differential effects of non-selective versus selective beta-blockade on myocardial substrate utilization in patients with CHF.

METHODS AND RESULTS

Twenty-two patients with CHF were randomised to the non-selective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurement of hemodynamics, arterial and coronary sinus free fatty acid (FFA) and lactate levels, and cardiac norepinephrine spillover (CANESP) were made before and after 4 months of therapy. In the carvedilol group (n=11), there was a significant reduction in myocardial FFA uptake (0.12+/-0.02 to 0.1+/-0.02 mmol/l, P<0.03). By contrast, in the metoprolol group (n=11) there was no change in myocardial FFA extraction. Carvedilol therapy tended to increase myocardial lactate extraction (0.24+/-0.05 to 0.35+/-0.08 mmol/l, P=0.08) while metoprolol therapy resulted in a trend in the opposite direction (0.18+/-0.03 to 0.11+/-0.04 mmol/l, P=0.09). The change in lactate extraction in the carvedilol group was significantly different from that in the metoprolol group (+0.11+/-0.06 vs. -0.09+/-0.04 mmol/l, P<0.01). Carvedilol treatment caused a significant reduction in CANESP while metoprolol had a neutral effect (-95+/-27 vs. 25+/-42 pmol/min, carvedilol vs. metoprolol P<0.03).

CONCLUSION

Carvedilol treatment caused a 20% reduction in myocardial free fatty acid extraction while metoprolol had a neutral effect. These differences are most probably related to the differential effects of these two agents on efferent cardiac sympathetic activity and may be relevant to the reported differential effects of these drugs on clinical outcomes.

摘要

背景

非选择性和选择性β受体阻滞剂已被证明可改善慢性心力衰竭（CHF）的预后。近期数据表明，非选择性β受体阻滞剂对预后的影响比β1选择性药物更有利。我们试图研究非选择性与选择性β受体阻滞剂对CHF患者心肌底物利用的不同影响。

方法与结果

22例CHF患者被随机分为非选择性β受体阻滞剂卡维地洛或选择性β受体阻滞剂美托洛尔组（双盲）。在治疗4个月前后测量血流动力学、动脉和冠状窦游离脂肪酸（FFA）及乳酸水平，以及心脏去甲肾上腺素溢出（CANESP）。在卡维地洛组（n = 11），心肌FFA摄取显著降低（从0.12±0.02降至0.1±0.02 mmol/L，P<0.03）。相比之下，在美托洛尔组（n = 11），心肌FFA提取无变化。卡维地洛治疗倾向于增加心肌乳酸提取（从0.24±0.05增至0.35±0.08 mmol/L，P = 0.08），而美托洛尔治疗则导致相反趋势（从0.18±0.03降至0.11±0.04 mmol/L，P = 0.09）。卡维地洛组乳酸提取的变化与美托洛尔组显著不同（+0.11±0.06与 -0.09±0.04 mmol/L，P<0.01）。卡维地洛治疗使CANESP显著降低，而美托洛尔则无影响（-95±27与25±42 pmol/min，卡维地洛与美托洛尔，P<0.03）。