Chronic amlodipine treatment during the development of heart failure.
Chronic amlodipine treatment during the development of heart failure.
复制标题
心力衰竭发展期间的慢性氨氯地平治疗。
DOI：
10.1161/01.cir.98.16.1666
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发表时间：
1998
期刊：
影响因子：
37.8
通讯作者：
Dodd,MG
中科院分区：
文献类型：
--
作者：
Spinale,FG;Mukherjee,R;Krombach,RS;Clair,MJ;Hendrick,JW;Houck,WV;Hebbar,L;Kribbs,SB;Zellner,JL;Dodd,MG
背景：本研究考察了慢性氨氯地平治疗对充血性心力衰竭（CHF）动物模型静息和跑步机运动时左心室（LV）泵功能、全身血流动力学、神经激素状态和局部血流分布的影响。在另外一系列的体外研究中，检查了左室肌细胞的收缩功能。方法与结果：16头猪分别在正常对照条件下、慢性起搏诱导的心力衰竭（240 bpm， 3周，n=8）或慢性起搏加氨氯地平（1.5 mg·kg−1·d−1,n=8）后进行研究。环境静息条件下，CHF组左室脑卒中容积（mL）较正常对照降低（16±2比31±2，P<0.05），联合氨氯地平组增加（29±2，P<0.05）。静止时，全身和肺血管阻力（dyne·s−1·cm−5）随CHF升高（分别为3102±251比2156±66和1066±140比253±24，均P<0.05），而氨氯地平治疗降低（分别为2108±199和480±74，P<0.05）。对于CHF，左室卒中容量仍然减少，并且与跑步机运动期间心肌血流量减少40%相关，而慢性氨氯地平治疗使左室卒中容量正常化并改善心肌血流量。静息和运动诱导的血浆去甲肾上腺素水平在慢性氨氯地平治疗组中增加了5倍，而在慢性氨氯地平治疗组中则比CHF值降低了50%。静息血浆内皮素（fmol/mL）在CHF组较正常升高（10.4±0.9比3.1±0.3，P<0.05），氨氯地平组较正常降低（6.6±1.1，P<0.5）。CHF组左室心肌细胞缩短速度（μm/s）较正常组降低（39±1比64±1，P<0.05），慢性氨氯地平组增加（52±1，P<0.05）。结论：慢性氨氯地平治疗在发生CHF的模型中产生良好的血流动力学、神经激素和收缩作用。
Background—This study examined the effects of chronic amlodipine treatment on left ventricular (LV) pump function, systemic hemodynamics, neurohormonal status, and regional blood flow distribution in an animal model of congestive heart failure (CHF) both at rest and with treadmill exercise. In an additional series of in vitro studies, LV myocyte contractile function was examined.Methods and Results—Sixteen pigs were studied under normal control conditions and after the development of chronic pacing–induced CHF (240 bpm, 3 weeks, n=8) or chronic pacing and amlodipine (1.5 mg · kg−1· d−1, n=8). Under ambient resting conditions, LV stroke volume (mL) was reduced with CHF compared with the normal control state (16±2 versus 31±2,P<0.05) and increased with concomitant amlodipine treatment (29±2,P<0.05). At rest, systemic and pulmonary vascular resistance (dyne · s−1· cm−5) increased with CHF compared with the normal control state (3102±251 versus 2156±66 and 1066±140 versus 253±24, respectively, bothP<0.05) and were reduced with amlodipine treatment (2108±199 and 480±74, respectively,P<0.05). With CHF, LV stroke volume remained reduced and was associated with a 40% reduction in myocardial blood flow during treadmill exercise, whereas chronic amlodipine treatment normalized LV stroke volume and improved myocardial blood flow. Resting and exercise-induced plasma norepinephrine levels were increased by >5-fold in the CHF group and were reduced by 50% from CHF values with chronic amlodipine treatment. Resting plasma endothelin (fmol/mL) increased with CHF compared with the normal state (10.4±0.9 versus 3.1±0.3,P<0.05) and was reduced with amlodipine treatment (6.6±1.1,P<0.5). With CHF, LV myocyte velocity of shortening (μm/s) was reduced compared with normal controls (39±1 versus 64±1,P<0.05) and was increased with chronic amlodipine treatment (52±1,P<0.05).Conclusions—Chronic amlodipine treatment in this model of developing CHF produced favorable hemodynamic, neurohormonal, and contractile effects in the setting of developing CHF.