thromboxane-b2 and Retinopathy-of-Prematurity

The acute phase of oxygen-induced retinopathy is associated with vasoconstriction and occlusion of the retinal vessels. Because this acute vasoobliterative phase could be due to the inhibition in retinal vessels of the production of the potent vasodilator and antithrombotic metabolite prostacyclin, animal experiments were performed to assess this possibility. Eight litters of 27 kittens (four to six days of age) were used. Control kittens were left in room air; hyperoxic kittens were placed in 80% oxygen for 48 hours; recovery kittens were returned to room air for 24 hours following hyperoxic exposure. Following treatments, the animals were killed, retinas isolated, and prostaglandin formation assessed. Retinal tissues produced 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and thromboxane B2 from exogenous arachidonate. A significant (approximately 33%) reduction in retinal 6-keto-prostaglandin F1 alpha (the end product of prostacyclin) was observed both in the hyperoxic and recovery litter mates when compared with controls. Both of the experimental groups also demonstrated a reduction in total retinal prostanoids that paralleled the changes observed in prostacyclin, suggesting that the biochemical effect of hyperoxia on retinal vascular arachidonic acid metabolism occurred at the level of cyclooxygenase. A decrease in the local production of prostacyclin during hyperoxia is consistent with the histologic retinal changes observed during the acute phase of oxygen-induced retinopathy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Carbon Radioisotopes; Cats; Dinoprost; Dinoprostone; Disease Models, Animal; Epoprostenol; Humans; Infant, Newborn; Oxygen; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Retinal Vessels; Retinopathy of Prematurity; Thromboxane B2

Exposure to high oxygen (O2) concentrations, especially in the neonate, is associated with the development of pathologic syndromes characterized by vascular involvement including the retinopathy of prematurity. Some of the initial vascular changes observed appear consistent with a reduction in prostacyclin formation. Exposure of human umbilical arteries to oxygen resulted in more than 30% inhibition in the ability of the vessels to produce prostacyclin either from endogenous stores of arachidonic acid or from exogenously provided substrate. In contrast, hypoxia (which more closely approximates the fetal environment) resulted in more than 30% stimulation in the production of prostacyclin from either endogenous or exogenous arachidonic acid. When microsomes were prepared from treated arterial segments, these effects persisted. In vitro results suggest that neonates exposed to O2 after delivery may experience a marked decrease in vascular prostacyclin formation. Inhibition of the production of this potent vasodilator and antithrombotic metabolite could play an important role in the acute exudative phase of O2 toxicity.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Arteries; Butylated Hydroxytoluene; Dinoprost; Dinoprostone; Epoprostenol; Humans; In Vitro Techniques; Microsomes; Oxygen; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Retinopathy of Prematurity; Thromboxane B2; Umbilical Arteries