Mayer Björn, Holmer Stephan R, Hengstenberg Christian, Lieb Wolfgang, Pfeifer Michael, Schunkert Heribert
Medizinische Klinik II, Universitätsklinik Schleswig Holstein, Campus Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Int J Cardiol. 2005 Aug 18;103(2):182-6. doi: 10.1016/j.ijcard.2004.08.053.
In patients with severe heart failure (CHF), chronically elevated cytokine levels document a systemic inflammation. Experimental data suggest that activation of the beta-adrenergic system may participate in this inflammatory response. Herein, we studied as to whether beta-adrenergic blockade on top of standard CHF therapy affects plasma cytokine levels (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNFalpha]). Moreover, we studied if beta-blocker related changes of these cytokines correspond to changes in left ventricular (LV) function and exercise capacity.
In a prospective study, 21 patients with stable CHF (NYHA functional class II-III, ejection fraction <40%, mean age 57.6+/-12.4 years) were treated with captopril (100-150 mg/day), furosemide (40-120 mg/day), and/or digoxin (0.1-0.2 mg/day) for at least 1 month before they entered a 4 week run-in period in which dosages were kept unchanged. Metoprololsuccinate was administered in increasing dosages (up to 190 mg/day) for the following 3 months. Clinical, echocardiographic, spiroergometric, and biochemical changes were assessed at the start and the end of the run-in period as well as after 3 month of beta-blockade.
As compared to 210 healthy volunteers, CHF patients, prior to beta-blockade, presented with markedly elevated IL-6 (8.9+/-9.9 vs. 2.1+/-0.5 pg/ml; p<0.05) and TNFalpha levels (1.51+/-0.49 vs. 0.64+/-0.15 pg/ml; p<0.05) levels. In CHF patients, 3 month of beta-blockade lowered heart rate (84+/-14 vs. 68+/-12 bpm; p<0.01), systolic (131+/-7 vs. 118+/-6 mm Hg; p<0.01), and diastolic blood pressure (78+/-5 vs. 71+/-6 mm Hg; p<0.01). Spiroergometric determined VO2 max (17.8+/-4.5 vs. 19.8+/-4.3 ml/min kg; p=0.013) increased significantly during 3 month of beta-blockade. Moreover, LV functional parameters tended to improve but the interindividual response varied and changes were non-significant. Interestingly, IL-6 levels decreased markedly during beta-blockade (8.9+/-9.9 vs. 4.5+/-3.1 pg/ml; p=0.036), whereas TNFalpha levels remained unchanged. Moreover, significant positive correlations were found between decrease of IL-6 levels and left ventricular end diastolic diameters (r2=0.59; p=0.012), whereas an inverse correlation was found between the decrease of IL-6 and the increase of VO2 max (r2=0.54; p=0.037), respectively.
In heart failure patients, beta-blockade may lower IL-6 but not TNFalpha levels. Changes of IL-6 during beta-blockade may be related to changes of LV function and geometry.
在重度心力衰竭（CHF）患者中，细胞因子水平长期升高表明存在全身炎症。实验数据表明，β-肾上腺素能系统的激活可能参与了这种炎症反应。在此，我们研究了在标准CHF治疗基础上加用β-肾上腺素能阻滞剂是否会影响血浆细胞因子水平（白细胞介素-6 [IL-6] 和肿瘤坏死因子α [TNFα]）。此外，我们研究了这些细胞因子与β受体阻滞剂相关的变化是否与左心室（LV）功能和运动能力的变化相对应。
在一项前瞻性研究中，21例稳定型CHF患者（纽约心脏协会功能分级II-III级，射血分数<40%，平均年龄57.6±12.4岁）在进入为期4周的导入期之前至少1个月接受卡托普利（100-150 mg/天）、呋塞米（40-120 mg/天）和/或地高辛（0.1-0.2 mg/天）治疗，导入期内剂量保持不变。在接下来的3个月中，逐渐增加美托洛尔琥珀酸盐的剂量（最高至190 mg/天）。在导入期开始和结束时以及β受体阻滞剂治疗3个月后评估临床、超声心动图、运动心肺功能和生化变化。
与210名健康志愿者相比，CHF患者在β受体阻滞剂治疗前IL-6水平（8.9±9.9 vs. 2.1±0.5 pg/ml；p<0.05）和TNFα水平（1.51±0.49 vs. 0.64±0.15 pg/ml；p<0.05）显著升高。在CHF患者中，β受体阻滞剂治疗3个月可降低心率（84±14 vs. 68±12次/分钟；p<0.01）、收缩压（131±7 vs. 118±6 mmHg；p<0.01）和舒张压（78±5 vs. 71±6 mmHg；p<0.01）。运动心肺功能测定的最大摄氧量（17.8±4.5 vs. 19.8±4.3 ml/min·kg；p=0.013）在β受体阻滞剂治疗3个月期间显著增加。此外，LV功能参数有改善趋势，但个体间反应不同且变化无统计学意义。有趣的是，β受体阻滞剂治疗期间IL-6水平显著降低（8.9±9.9 vs. 4.
