Effect of bicarbonate on retinal vasculature and acidosis-induced retinopathy in the neonatal rat.
BACKGROUND
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 (AIR) are 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 AIR can be prevented with systemic bicarbonate treatment.


METHODS
The 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 and 20 mmol/kg once 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.


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 (28% survival) and 20 mmol/kg bicarbonate once daily (45% survival) had an incidence of preretinal NV of 9% and 8%, respectively. No NV was seen in saline-control rats. In the acetazolamide-treated rats, the incidence of preretinal NV in surviving rats was numerically lower in bicarbonate-treated rats than acetazolamide-only controls (8% versus 24%, p=0.065) but with only 19% survival in the bicarbonate-treated rats.


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 may reduce the incidence of preretinal NV, treatment was associated with an unacceptable mortality rate.
Berdahl
John P
JP
Mayo Medical School, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Leske
David A
DA
Fautsch
Michael P
MP
Lanier
William L
WL
Holmes
Jonathan M
JM
D000086:Acetazolamide; D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002257:Carbonic Anhydrase Inhibitors; D004195:Disease Models, Animal; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D007274:Injections, Intraperitoneal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D017693:Sodium Bicarbonate / Q000627:therapeutic use*
D002257:Carbonic Anhydrase Inhibitors; D017693:Sodium Bicarbonate; D000086:Acetazolamide