卡维地洛治疗心力衰竭患者时的脑钠肽、内皮素-1、促炎细胞因子（肿瘤坏死因子-α、白细胞介素-6）浓度及运动能力

Concentration of BNP, endothelin 1, pro-inflammatory cytokines (TNF-alpha, IL-6) and exercise capacity in patients with heart failure treated with carvedilol.

作者信息

Nessler Jadwiga, Nessler Bohdan, Kitliński Mariusz, Gackowski Andrzej, Piwowarska Wiesława, Stepniewski Marek

机构信息

Institute of Cradiology, Collegium Medicum, Jagiellonian University, Krakow, Poland.

出版信息

Kardiol Pol. 2008 Feb;66(2):144-51; discussion 152-3.

PMID:18344152

Abstract

BACKGROUND

Recent studies on the pathophysiology of heart failure indicate the role of neurohormones and immune and inflammatory processes as potential mechanisms involved in the pathogenesis and clinical course of chronic heart failure (CHF).

AIM

To analyse the relationship between concentrations of brain natriuretic peptide (BNP), endothelin-1 (ET-1), inflammatory cytokines (TNF-alpha, IL-6) and cardiopulmonary stress test parameters, and to evaluate their changes during carvedilol treatment.

METHODS

The study included 86 patients (81 men and 5 women) aged from 35 to 70 years (56.8+/-9.19) with symptomatic heart failure and left ventricular ejection fraction <40%, receiving an inhibitor of angiotensin II converting enzyme, diuretic and/or digoxin but not beta-blockers. All patients at baseline, and then at 3 and 12 months after treatment, underwent a panel of studies to assess functional capacity according to NYHA, echocardiographic and cardiopulmonary stress test (CPX) parameters, and serum concentrations of BNP, ET-1, TNF-alpha and IL-6. Before introducing carvedilol we found a weak relationship between concentrations of BNP, ET-1, IL-6 and decreased VO2 peak.

RESULTS

At 12 months exercise tolerance was significantly improved (exercise stress testing prolonged by 143.9 s, p=0.001) and an increase in metabolic equivalent (MET) by 1.41 (p=0.001) was observed. The VO2 peak was nonsignificantly increased by a mean of 0.9 ml/kg/min. In patients with baseline VO2 peak <14 ml/kg/min the concentrations of ET-1 and TNF-alpha were significantly higher than in the remaining ones, and after treatment they were significantly reduced. In these patients VO2 peak%N was also significantly increased (39.5+/-7.5 vs. 50.1+/-15,0; p=0.013). The number of patients with VO2 peak <14 ml/kg/min also significantly decreased from 39 to 21 (p=0.013).

CONCLUSIONS

In patients with HF decreased value of VO2 peak is associated with LV systolic function disorders and increased levels of BNP, ET-1, TNF-alpha and IL-6. Chronic treatment with carvedilol improves LV systolic function, exercise tolerance and peak oxygen consumption and is associated with significant decrease of BNP, ET-1, TNF-alpha and IL-6 concentrations.

摘要

背景

近期关于心力衰竭病理生理学的研究表明，神经激素以及免疫和炎症过程在慢性心力衰竭（CHF）的发病机制和临床病程中作为潜在机制发挥作用。

目的

分析脑钠肽（BNP）、内皮素-1（ET-1）、炎性细胞因子（TNF-α、IL-6）浓度与心肺应激试验参数之间的关系，并评估卡维地洛治疗期间它们的变化。

方法

该研究纳入了86例年龄在35至70岁（56.8±9.19）的患者（81例男性和5例女性），这些患者有症状性心力衰竭且左心室射血分数<40%，正在接受血管紧张素II转换酶抑制剂、利尿剂和/或地高辛治疗，但未使用β受体阻滞剂。所有患者在基线时，以及治疗后3个月和12个月时，接受了一系列检查，以根据纽约心脏协会（NYHA）评估功能能力、超声心动图和心肺应激试验（CPX）参数，以及BNP、ET-1、TNF-α和IL-6的血清浓度。在引入卡维地洛之前，我们发现BNP、ET-1、IL-6浓度与VO2峰值降低之间存在微弱关系。

结果

在12个月时，运动耐量显著改善（运动应激试验延长了143.9秒，p = 0.001），且观察到代谢当量（MET）增加了1.41（p = 0.001）。VO2峰值平均非显著性增加了0.9 ml/kg/min。在基线VO2峰值<14 ml/kg/min的患者中，ET-1和TNF-α的浓度显著高于其余患者，治疗后它们显著降低。在这些患者中，VO2峰值%N也显著增加（39.5±7.5对50.1±15.0；p = 0.013）。VO2峰值<14 ml/kg/min的患者数量也从39例显著减少至21例（p = 0.013）。