The effect of the prostaglandin I2 analogue OP-2507 on adrenaline-induced pulmonary edema in rabbits and analysis of hemodynamic changes.
This study was carried out to understand the onset mechanism of adrenaline (ADR)-induced pulmonary edema (PE) and the effect of drugs related to the arachidonate cascade in a rabbit model. ADR was administered intravenously by a bolus injection to the rabbits at 50, 75 and 100 microg/kg. To evaluate the severity of PE, the lung-water ratio (LWR) was calculated as a ratio of the difference between wet and dry lung weight to dry lung weight. The PE incidence and LWR exhibited a dose-dependent increase, and LWR correlated with the left atrial pressure (LAP). The involvement of the arachidonate cascade was evaluated by the co-administration of flurbiprofen, a cyclooxygenase inhibitor; ozagrel, a thromboxane synthase inhibitor; and OP-2507 (15-cis-(4-n-propylcyclohexyl)-6,17,18, 19,20-pentanor-9-deoxy-6,9-alpha-nitriloprostaglandin F1 methyl ester), a prostaglandin I2 analogue. Co-treatment of the rabbits with ADR and flurbiprofen resulted in an increase in LAP and the incidence of PE, whereas co-administration of ozagrel did not exhibit any significant changes in the measured parameters. Conversely, OP-2507 reduced the LAP, PE incidence and LWR when co-administered with ADR. Rabbits co-treated with OP-2507 displayed an improved cardiac function. The results of these studies demonstrated the effectiveness of OP-2507 in protecting the lung and cardiac function from the ADR-induced PE.
Department of Preventive Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
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A
Miura
Y
Y
Hao
Y
Y
Koike
L M
LM
Wang
Y
Y
Honda
S
S
Mineshita
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000009:adverse effects* / Q000097:blood; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005480:Flurbiprofen / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D023421:Models, Animal; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000503:physiopathology*; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D008689:Methacrylates; D005480:Flurbiprofen; C049453:OP 2507; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel; D004837:Epinephrine