Sabbah H N, Haddad W, Mika Y, Nass O, Aviv R, Sharov V G, Maltsev V, Felzen B, Undrovinas A I, Goldstein S, Darvish N, Ben-Haim S A
Department of Medicine & Division of Cardiovascular Medicine, Henry Ford Heart & Vascular Institute, Detroit, Michigan USA.
Heart Fail Rev. 2001 Jan;6(1):45-53. doi: 10.1023/a:1009855208097.
The intravenous use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and positive chronotropic effects. Chronic use of these agents, while eliciting an improvement in the quality of life of patients with advanced heart failure, has been abandoned because of marked increase in mortality when compared to placebo. Nevertheless, patients with advanced heart failure can benefit from long-term positive inotropic support if the therapy can be delivered 'on demand' and in a manner that is both safe and effective. In this review, we will examine the use of a novel, non-stimulatory electrical signal that can acutely modulate left ventricular (LV) contractility in dogs with chronic heart failure in such a way as to elicit a positive inotropic support. Cardiac contractility modulation (CCM) with the Impulse Dynamic(trade mark) signal was examined in dogs with chronic heart failure produced by intracoronary microembolizations. Delivery of the CCM signal from a lead placed in the great coronary vein for periods up to 10 minutes resulted in significant improvements in cardiac output, LV peak+dP/dt, LV fractional area of shortening and LV ejection fraction measured angiographically. Discontinuation of the signal resulted in a return of all functional parameters to baseline values. In cardiomyocytes isolated from dogs with chronic heart failure, application of the CCM signal resulted in improved shortening, rate of change of shortening and rate of change of relengthening suggesting that CCM application is associated with intrinsic improvement of cardiomyocyte function. The improvement in isolated cardiomyocyte function after application of the CCM signal was accompanied by an increase in the peak and integral of the Ca(2+) transient suggesting modulation of calcium cycling by CCM application. In a limited number of normal dogs, intermittent chronic delivery of the CCM signal for up to 7 days showed chronic maintenance of LV functional improvement. In conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal indicate that this non-pharmacologic therapeutic modality can provide short-term positive inotropic support to the failing heart and as such, may be a useful adjunct in the treatment of advanced heart failure. Additional, long-term studies in dogs with heart failure are needed to establish the safety and efficacy of this therapeutic modality for the chronic treatment of this disease syndrome.
在心力衰竭中，静脉使用正性肌力药物，如拟交感神经药和磷酸二酯酶抑制剂，会受到促心律失常和正性变时作用的限制。长期使用这些药物，虽然能改善晚期心力衰竭患者的生活质量，但与安慰剂相比，由于死亡率显著增加，已被弃用。然而，如果治疗能够“按需”进行，并且以安全有效的方式提供，晚期心力衰竭患者可以从长期正性肌力支持中获益。在这篇综述中，我们将研究一种新型的非刺激性电信号的应用，该信号可以急性调节慢性心力衰竭犬的左心室（LV）收缩力，从而产生正性肌力支持。使用脉冲动力（商标）信号进行心脏收缩力调制（CCM），对冠状动脉内微栓塞诱导的慢性心力衰竭犬进行了研究。将CCM信号从置于大冠状静脉的导线传输长达10分钟，结果显示心输出量、LV峰+dP/dt、LV缩短分数面积和血管造影测量的LV射血分数有显著改善。信号停止后，所有功能参数恢复到基线值。在从慢性心力衰竭犬分离的心肌细胞中，应用CCM信号导致缩短改善、缩短变化率和再延长变化率提高，表明CCM应用与心肌细胞功能的内在改善有关。应用CCM信号后分离的心肌细胞功能改善伴随着Ca(2+)瞬变峰值和积分的增加，表明CCM应用可调节钙循环。在少数正常犬中，间歇性慢性传输CCM信号长达7天显示LV功能改善得以长期维持。总之，迄今为止，脉冲动力CCM信号的临床前结果表明，这种非药物治疗方式可为衰竭心脏提供短期正性肌力支持，因此，可能是治疗晚期心力衰竭的有用辅助手段。需要对心力衰竭犬进行更多的长期研究，以确定这种治疗方式对该疾病综合征慢性治疗的安全性和有效性。
