Sasayama S, Yokawa S, Akiyama M, Mikawa M, Sakai O
Jpn Circ J. 1986 Jul;50(7):636-43. doi: 10.1253/jcj.50.636.
Effects of a new selective beta1 partial agonist, ICI 118,587, on cardiac function were assessed in clinical settings. In 7 patients, responses to multistage treadmill exercise were studied before and after an acute intravenous injection of the drug. The heart rate and blood pressure were not altered by ICI 118,587 at rest but increases in both parameters in response to exercise were significantly reduced. Neither oxygen consumption nor plasma norepinephrine level was modified by the drug both at rest and during exercise. The long term effects of ICI 118,587 were assessed in 6 patients with mild to moderate cardiac failure consequent upon ischemic heart disease. After chronic administration of the drug exercise duration was increased. The symptom-limited maximal oxygen consumption increased by 16%, associated with prolongation of the exercise tolerance. In those patients who also had symptoms of angina pectoris, exercise levels which caused angina during the control study were tolerated without symptoms after ICI 118,587. Twelve patients with nocturnal bradycardia resulting from atrial fibrillation of sick sinus syndrome were treated with ICI 118,587. Monitoring of heart rate by 24-hour Holter ECG showed that ICI 118,587 increased minimal heart rate during sleep. Being a beta1-adrenoceptor partial agonist, it has both agonist and antagonist properties. Thus, ICI 118,587 buffers the heart from an excessively low sympathetic tone which may occur during sleep and from an excessively high tone during exercise. It appears to be of benefit in the treatment of mild to moderate cardiac failure consequent upon ischemic heart disease. It also improves oxygen demand-supply imbalance without inducing further myocardial depression or inappropriate bradycardia at rest. ICI 118,587 may therefore be described as a cardiostabilizer.
在临床环境中评估了一种新型选择性β1部分激动剂ICI 118,587对心脏功能的影响。对7名患者在急性静脉注射该药物前后进行多级跑步机运动的反应进行了研究。ICI 118,587在静息时未改变心率和血压，但运动时这两个参数的增加显著减少。药物在静息和运动时均未改变耗氧量和血浆去甲肾上腺素水平。在6名因缺血性心脏病导致轻至中度心力衰竭的患者中评估了ICI 118,587的长期影响。长期给药后运动持续时间增加。症状限制下的最大耗氧量增加了16%，同时运动耐力延长。在那些也有心绞痛症状的患者中，在对照研究期间引起心绞痛的运动水平在使用ICI 118,587后可以无症状耐受。12名因病态窦房结综合征房颤导致夜间心动过缓的患者接受了ICI 118,587治疗。通过24小时动态心电图监测心率显示，ICI 118,587增加了睡眠期间的最低心率。作为一种β1肾上腺素能受体部分激动剂，它具有激动剂和拮抗剂特性。因此，ICI 118,587可使心脏免受睡眠期间可能出现的过低交感神经张力以及运动期间过高张力的影响。它似乎对治疗缺血性心脏病导致的轻至中度心力衰竭有益。它还改善了氧供需失衡，而不会在静息时引起进一步的心肌抑制或不适当的心动过缓。因此，ICI 118,587可被描述为一种心脏稳定剂。
