THE RANGE OF PAO2 VARIATION DETERMINES THE SEVERITY OF OXYGEN-INDUCEDRETINOPATHY IN NEWBORN RATS

Purpose. This study was conducted to determine the potential influence of PaO2 fluctuation on the retinal neovascular response known to occu r in newborn rats exposed to hyperoxic conditions. As an inherent coro llary, the authors also defined the relationship between the fraction of inspired oxygen (FiO(2)) and the arterial blood oxygen tension (PaO 2) in newborn rats. Methods. Experiment 1 was composed of several oxyg en-exposure protocols in which atmospheres of 10% oxygen concentration were alternated with different higher levels of ambient oxygen (50%, 40%, 30%, and room air). In experiment 2, two alternating oxygen conce ntrations were made to converge toward room air (20.9% oxygen) with ea ch successive group of four treatment groups. These included another g roup exposed to alternating 50% and 10% oxygen, a group exposed to alt ernating 45% and 12.5% oxygen concentrations, one exposed to alternati ng concentrations of 40% and 15% oxygen, and a final group exposed to 35% and room air oxygen concentrations. In each case, oxygen rs-as alt ernated between the two exposure concentrations every 24 hours. The te rm Delta FiO(2) is used to designate the difference in the two oxygen concentrations to which a treatment group was subjected, applying the units of fraction of inspired oxygen (i.e., Delta FiO(2) = 0.4 for the exposure to alternating 50% and 10% oxygen). At birth, litters of alb ino rats were placed in each of these environments for 13 or 14 days, after which PaO2 and retinal vascular development were assessed in som e rats, The remainder were removed to room air for 4 days before the i ncidence and severity of abnormal neovascularization were measured. Re sults. PaO2 and FiO(2) were directly and linearly correlated (r(2) = 0 .998). In experiment 1, the extent of retinal vascular development on removal from oxygen was a linear function of Delta FiO(2). Retinal neo vascularization subsequently occurred in all rats exposed to alternati ng 50% and 10% or 40% and 10% oxygen concentrations, but only a third of the 30% and 10% exposure group, indicating a minimum threshold for proliferative disease at Delta FiO(2) = 0.2. In experiment 2, retinal avascularity also increased linearly with increasing Delta FiO(2). The re was a threshold for neovascularization between the exposure to alte rnating 45% and 12.5% oxygen and the 40% and 15% oxygen exposure (100% versus 4.8% incidence of neovascularization), indicating a requiremen t of less than or equal to 12.5% oxygen episodes to stimulate a consis tent proliferative response. Conclusions. These results suggest that P aO2 fluctuation and degree of hypoxia may have more influence on proli ferative retinal disease in newborn rats than the extended hyperoxia t hat has historically received greater attention. Experimental designs that address the inherent differences in pulmonary function between in trinsically healthy animals and compromised premature infants are of s ubstantial value to our understanding of the pathogenesis of retinopat hy of prematurity.