Akinori Miura, Yu Hao, Yuuichi Koike, Li-Man Wang, Yumiko Honda and Satoru
Mineshita
Department of Preventive Medicine, Division of Social Medicine, Medical
Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima,
Bunkyo-ku, Tokyo 113-8510, Japan
Abstract: 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ﾊmg/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)-16,17,18,19,20-pentanor-9-deoxy-6,9-a-nitriloprostaglandinﾊF1
methyl ester), a prostaglandinﾊ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.
Keywords: Adrenaline, Pulmonary edema, Heart failure, Cyclooxygenase
inhibitor, Prostaglandin I2 analogue