Abstract 2797: Role of Nitric Oxide in Placental Dysfunction Following Fetal Cardiopulmonary Bypass
Introduction Placental dysfunction following fetal cardiopulmonary bypass remains the Achilles heel of fetal cardiac surgery. The etiology of the placental dysfunction is unknown. Indirect evidence implicates the placental nitric oxide (NO) pathway in the pathogenesis of this problem and the subsequent fetal demise. Therefore we directly measured in vivo NO concentration during fetal bypass, along with plasma levels of cyclic GMP and NO metabolites.
Methods Ovine fetuses 100–104 day gestational age were placed on bypass for a period of 30 minutes and followed post-bypass for 2 hours. Fetal plasma samples were taken every 15–30 minutes and analyzed for total NO metabolite levels (Nitrite & Nitrate) and cyclic GMP levels by immunoassay. Real time NO concentration was assessed with an inNO-T Nitric Oxide measurement system (Harvard Apparatus; Holliston, MA) placed in the common umbilical vein. Measured changes in NO concentration were correlated to initiation and termination of bypass, to umbilical flows and to fetal arterial blood gas values. Statistical analysis was performed using Student’s t-test (2-tailed), with significance declared at p<0.05.
Results There was a significant linear increase in cyclic GMP levels and a decline in NO metabolite concentrations from baseline, fetal bypass period, and the post bypass recovery. The levels are statistically higher then baseline (p<0.05 for all). The preceding correlated with a marked but transient increase in umbilical venous NO concentration measured (32.5±20.0%, Mean±SD), followed by a persistent and significant decline in NO levels (-56.3±20.9%) (p<0.05 for both). Furthermore, the decline in NO concentration correlated with decreasing umbilical flows and worsening fetal respiratory acidosis (pCO2>70; normal controls = 50mmHg).
Conclusion Fetal bypass results in an increase in cyclic GMP levels and a marked decline in total NO metabolite levels. Initiation of fetal bypass causes an unexpected transient increase in NO concentration followed by a marked and persistent decrease in NO concentration post bypass. The preceding suggest a significant derangement in placental NO pathway in response to fetal bypass.