Lilleberg J, Sundberg S, Nieminen M S
First Department of Medicine, Helsinki University Hospital, Finland.
J Cardiovasc Pharmacol. 1995;26 Suppl 1:S63-9.
Levosimendan, a new drug that sensitizes troponin-C to calcium and selectively inhibits phosphodiesterase III, was administered to 24 patients with ischemic heart disease and ejection fraction below 40%. In a placebo-controlled, crossover, double-blind study, each patient received two intravenous doses of levosimendan on 2 consecutive study days. The doses were 0.25 mg (n = 6), 0.5 mg (n = 11), 1 mg (n = 12), 2 mg (n = 12), and 4 mg (n = 5). After 0.25 mg and 0.5 mg, cardiac output increased by 0.49-0.67 L/min (p < 0.05) due to an increase in stroke volume of 6-11 ml. After 2 and 4 mg, cardiac output increased by 0.61-0.88 L/min due to an increase in heart rate of 6-12 beats/min. The baseline filling pressures, i.e., right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP), were within the normal range. RAP decreased significantly (p < 0.05) after 2 and 4 mg and PCWP after 0.5, 1, 2, and 4 mg. The most profound decreases were observed 10 min after infusion of 4 mg, from 5.0 to 3.2 mm Hg in RAP and from 9.8 to 6.0 mm Hg in PCWP. Total peripheral resistance decreased significantly only after 2 and 4 mg, by 13 and 21%, respectively. However, there were no statistically significant changes in pulmonary vascular resistance. It is concluded that levosimendan has a hemodynamically favorable action after 0.25 and 0.5 mg but that decreases in filling pressures probably prevented the increase in stroke volume and caused a reflex increase in heart rate after 2 and 4 mg.
左西孟旦是一种能使肌钙蛋白C对钙敏感并选择性抑制磷酸二酯酶III的新药，对24例缺血性心脏病且射血分数低于40%的患者进行了用药治疗。在一项安慰剂对照、交叉、双盲研究中，每位患者在连续2个研究日接受了两剂静脉注射的左西孟旦。剂量分别为0.25毫克（n = 6）、0.5毫克（n = 11）、1毫克（n = 12）、2毫克（n = 12）和4毫克（n = 5）。给予0.25毫克和0.5毫克后，心输出量增加了0.49 - 0.67升/分钟（p < 0.05），这是由于每搏输出量增加了6 - 11毫升。给予2毫克和4毫克后，心输出量增加了0.61 - 0.88升/分钟，这是由于心率增加了6 - 12次/分钟。基线充盈压，即右心房压力（RAP）和肺毛细血管楔压（PCWP），均在正常范围内。给予2毫克和4毫克后RAP显著降低（p < 0.05），给予0.5毫克、1毫克、2毫克和4毫克后PCWP降低。在输注4毫克后10分钟观察到最显著的下降，RAP从5.0毫米汞柱降至3.2毫米汞柱，PCWP从9.8毫米汞柱降至6.0毫米汞柱。仅在给予2毫克和4毫克后总外周阻力显著降低，分别降低了13%和21%。然而，肺血管阻力没有统计学上的显著变化。得出的结论是，0.25毫克和0.5毫克的左西孟旦具有血流动力学上有利的作用，但充盈压的降低可能阻止了每搏输出量的增加，并导致给予2毫克和4毫克后心率反射性增加。
