Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs

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• 作者：Atsushi Honda^a ; Yuji Nakamura^a ; Hiroshi Ohara^b ; Xin Cao^a ; Hiroaki Nomura^a ; Jun Katagi^a ; Takeshi Wada^a ; Hiroko Izumi-Nakaseko^a ; Kentaro Ando^a ; Atsushi Sugiyama^a ; ^{atsushi.sugiyama@med.toho-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：eNOS ; endothelial nitric oxide synthase ; Emax ; maximum elastance ; Emin ; minimum elastance ; EP1 ; 2 ; 3 and 4 ; prostaglandin E2 type 1 ; 2 ; 3 and 4 ; HFpEF ; heart failure with preserved ejection fraction ; HFrEF ; heart failure with reduced ejection fraction ; ONO-AE1-329 ; 16-(3-Methoxymethyl)phenyl-ω-tetranor-3 ; 7-dithia PGE1 ; peak +dP/dt ; maximum upstroke velocity of the left ventricular pressure ; peak &minus ; dP/dt ; maximum downstroke velocity of the left ventricular pressure ; Tau ; isovolumic relaxati
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：775
• 期：Complete
• 页码：130-137
• 全文大小：1491 K

文摘

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4–5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction.