Kubota T, Itaya R, Todaka K, Sugimachi M, Sunagawa K, Takeshita A
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University, Fukuoka, Japan.
Arzneimittelforschung. 1991 Dec;41(12):1211-5.
Beneficial effects of cardiotonic phosphodiesterase inhibitors on congestive heart failure are possibly mediated in part by a reduction of afterload. 1,2-Dihydro-5-imidazo[1,2-a]pyridin-6-yl-6-methyl-2-oxo-3- pyridinecarbonitrile hydrochloride monohydrate (E-1020, CAS 119615-63-3), a new cardiotonic phosphodiesterase inhibitor was evaluated for its effect on aortic input impedance in eight anesthetized open-chest dogs. First instantaneous aortic pressure and flow under random ventricular pacing before and after E-1020 infusions (10, 30, and 100 micrograms/kg i.v.) were measured. Then aortic input impedance over the frequency range of 0.024 to 20 Hz was estimated using a multichannel autoregressive model. With the infusion of E-1020, aortic input impedance was decreased in the low frequency range (below 0.1 Hz) and shifted leftward in the transitional frequency range (from 0.1 to 2 Hz), while it remained unchanged in the high frequency range (above 2 Hz). Parameterization of the aortic input impedance using a three-element Windkessel model indicated that E-1020 (at a dose of 100 micrograms/kg i.v.) decreased arterial resistance by 35% (p less than 0.01) and increased arterial compliance by 12% (p less than 0.01). It is concluded that E-1020 improves cardiac performance by unloading static and dynamic afterload in addition to its cardiotonic effect.
强心磷酸二酯酶抑制剂对充血性心力衰竭的有益作用可能部分是通过降低后负荷介导的。对一种新型强心磷酸二酯酶抑制剂1,2 -二氢-5-咪唑并[1,2 - a]吡啶-6-基-6-甲基-2-氧代-3-吡啶甲腈盐酸盐一水合物（E - 1020，CAS 119615 - 63 - 3）在八只麻醉开胸犬中评估了其对主动脉输入阻抗的影响。首先测量了E - 1020静脉输注（10、30和100微克/千克）前后随机心室起搏时的瞬时主动脉压力和流量。然后使用多通道自回归模型估计0.024至20 Hz频率范围内的主动脉输入阻抗。随着E - 1020的输注，低频范围（低于0.1 Hz）的主动脉输入阻抗降低，过渡频率范围（从0.1至2 Hz）向左移动，而高频范围（高于2 Hz）保持不变。使用三元风箱模型对主动脉输入阻抗进行参数化表明，E - 1020（静脉注射剂量为100微克/千克）使动脉阻力降低35%（p小于0.01），动脉顺应性增加12%（p小于0.01）。得出的结论是，E - 1020除了具有强心作用外，还通过减轻静态和动态后负荷来改善心脏功能。
