TY - JOUR
T1 - Effects of the new cardiotonic phosphodiesterase inhibitor 1,2-dihydro-5-imidazo[1,2-a]pyridin-6-yl-6-methyl-2-oxo-3-pyridine-car bonitrile hydrochloride monohydrate on aortic input impedance
AU - Kubota, T.
AU - Itaya, R.
AU - Todaka, K.
AU - Sugimachi, M.
AU - Sunagawa, K.
AU - Takeshita, A.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1991
Y1 - 1991
N2 - 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-pyridine-car bonitrile 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 μg/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 μg/kg i.v.) decreased arterial resistance by 35% (p < 0. 01) and increased arterial compliance by 12% (p < 0. 01). It is concluded that E-1020 improves cardiac performance by unloading static and dynamic afterload in addition to its cardiotonic effect.
AB - 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-pyridine-car bonitrile 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 μg/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 μg/kg i.v.) decreased arterial resistance by 35% (p < 0. 01) and increased arterial compliance by 12% (p < 0. 01). It is concluded that E-1020 improves cardiac performance by unloading static and dynamic afterload in addition to its cardiotonic effect.
UR - http://www.scopus.com/inward/record.url?scp=0026088453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026088453&partnerID=8YFLogxK
M3 - Article
C2 - 1815518
AN - SCOPUS:0026088453
VL - 41
SP - 1211
EP - 1215
JO - Drug Research
JF - Drug Research
SN - 2194-9379
IS - 12
ER -