Abstract
Abstract: :
Purpose: Systemic acidosis induces preretinal neovascularization (NV) analogous to retinopathy of prematurity (ROP) in the neonatal rat. Sodium bicarbonate is used in human neonates to treat acidosis. The effects of alkali administration on the developing retinal vasculature and on acidosis–induced retinopathy is unknown. We investigated the effect of sodium bicarbonate gavage on the retinal vasculature of normal and acidotic neonatal rats to determine 1) whether bicarbonate treatment is associated with preretinal NV and 2) whether acidosis–induced retinopathy (AIR) can be prevented with systemic bicarbonate treatment. Methods: Extent of acidosis and alkalosis were initially determined from carotid arterial blood samples. In the bicarbonate alone study, newborn rats were randomized into litters of 25 and received bicarbonate doses of 15 mmol/kg twice daily, 20 mmol/kg once daily, or 20 mmol/kg twice daily from days 2 to 7. Control animals received saline gavage. In the AIR treatment study, acidosis was induced in neonatal rats by intraperitoneal injection of acetazolamide 200 mg/kg from days 2 to 7. Acetazolamide–treated rats received either additional bicarbonate gavage or no additional treatment. Eyes were enucleated on day 13 and the retinal vasculature was assessed for NV using ADPase staining techniques and light microscopy in a masked manner. Results: Systemic alkalosis (peak pH = 7.55 ± 0.02; mean ± SD) was confirmed with bicarbonate gavage and partial reversal of acidosis was confirmed when acetazolamide–treated rats received bicarbonate. Surviving rats receiving bicarbonate 15 mmol/kg twice daily and 20 mmol/kg bicarbonate once daily had an incidence of preretinal NV of 9% and 8% respectively. No NV was seen in saline control rats or rats receiving bicarbonate 20 mmol/kg twice daily, but mortality with bicarbonate at 20 mmol/kg twice daily was very high (81% vs. 36% in controls). In the AIR treatment study, the incidence of preretinal NV in surviving rats was lower in bicarbonate treated rats than controls (8% vs. 24%). Conclusions: In the neonatal rat, alkalosis induced by bicarbonate gavage is associated with a low incidence of mild preretinal NV similar to ROP. Although treating acidotic rats with bicarbonate reduced the incidence of preretinal NV, it was associated with an unacceptable mortality rate. Our results may have implications for the management of systemic acid–base imbalance in human infants at risk for ROP.
Keywords: retinal neovascularization • retinopathy of prematurity • drug toxicity/drug effects