Bhargava V, Shabetai R, Mathiäsen R A, Dalton N, Hunter J J, Ross J
University of California San Diego, USA.
Am J Cardiol. 1998 May 1;81(9):1130-7. doi: 10.1016/s0002-9149(98)00133-7.
This study was designed to determine whether the force-frequency effect on myocardial contractility, known to be importantly regulated by the adrenergic nervous system in experimental animals, can be enhanced by beta-adrenergic receptor stimulation in patients with heart failure. Animal experiments have demonstrated that the positive force-frequency relation in most mammals is subject to enhancement by beta-adrenergic receptor stimulation during exercise or infusion of a beta-receptor agonist. In animal models of heart failure, this regulatory mechanism generally is lost. The response to progressive increases in heart rate to 150 to 160 beats/min by right atrial pacing before and during dobutamine infusion was studied in 3 relatively normal subjects and in 5 patients with severe dilated cardiomyopathy. Left ventricular (LV) pressure and its first derivative (LV dP/dt(max)) were measured with a micromanometer, and the time constant of LV relaxation was assessed. The slopes of the relations between heart rate and LV dP/dt(max) in control subjects were positive at baseline and the mean slope increased substantially and significantly during dobutamine infusion. In patients with heart failure, the heart rate versus LV dP/dt(max) relations were depressed and flattened without a descending limb. Dobutamine infusion shifted this relation upward slightly, without increase in mean slope, indicating lack of amplification. The rate of isovolumic relaxation significantly decreased as heart rate increased at baseline and was further shortened by dobutamine. In patients with heart failure, a depressed and flattened relation between heart rate and LV dP/dt(max) (force-frequency effect) did not show the amplification of myocardial contractility by beta-adrenergic stimulation observed in the normal heart. This abnormality in control of the force-frequency relation undoubtedly plays an important role in the impairment of cardiac function during exercise in heart failure.
本研究旨在确定在实验动物中已知由肾上腺素能神经系统重要调节的心肌收缩力的力-频率效应，在心力衰竭患者中是否可通过β-肾上腺素能受体刺激而增强。动物实验表明，大多数哺乳动物中的正向力-频率关系在运动期间或输注β受体激动剂时会受到β-肾上腺素能受体刺激的增强作用。在心力衰竭的动物模型中，这种调节机制通常会丧失。在3名相对正常的受试者和5名严重扩张型心肌病患者中，研究了在多巴酚丁胺输注前和期间通过右心房起搏使心率逐渐增加至150至160次/分钟时的反应。用微测压计测量左心室（LV）压力及其一阶导数（LV dP/dt(max)），并评估LV舒张的时间常数。对照组受试者心率与LV dP/dt(max)之间关系的斜率在基线时为正，在多巴酚丁胺输注期间平均斜率显著增加。在心力衰竭患者中，心率与LV dP/dt(max)的关系降低且变平，没有下降支。多巴酚丁胺输注使这种关系略有上移，但平均斜率没有增加，表明缺乏放大作用。在基线时，等容舒张速率随着心率增加而显著降低，多巴酚丁胺使其进一步缩短。在心力衰竭患者中，心率与LV dP/dt(max)（力-频率效应）之间降低且变平的关系未显示出正常心脏中观察到的β-肾上腺素能刺激对心肌收缩力的放大作用。力-频率关系控制中的这种异常无疑在心力衰竭患者运动期间的心功能损害中起重要作用。
