The Effect of the Prostaglandin I₂ Analogue OP-2507 on Adrenaline-Induced Pulmonary Edema in Rabbits and Analysis of Hemodynamic Changes

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 100μg/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−α−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.