Cytokine Response to Fetal Cardiac Bypass

>Objective: Cytokines are associated with the systemic inflammatory response syndrome that occurs after cardiopulmonary bypass. We hypothesized that the placental dysfunction which has been found to complicate fetal cardiac bypass may be in part a function of a cytokine-mediated acute phase reaction. To test this hypothesis, we designed a study to investigate the effect of cardiac bypass on interleukin-1beta (IL-1beta), IL-6, and IL-8 in fetal sheep.Methods: Nine mixed-breed pregnant ewes at 118-122 days of gestation were assigned randomly to either the "fetal cardiac bypass group" (n = 5) or the "control group" (n = 4). After surgical exposure and instrumentation, cardiac bypass was performed for 30 min in study group fetuses, whereas control group fetuses were exposed and instrumented identically but did not undergo bypass. Placental and systemic hemodynamics were monitored in both groups. Pre- and post-bypass blood samples were analyzed for IL-1beta, IL-6, and IL-8 using enzyme-linked immunosorbent assays.Results: IL-6 levels were undetectable before bypass in all fetuses. IL-6 increased after bypass in all bypass group fetuses to 53.0 +/- 24.2 pg/ml, whereas IL-6 levels remained undetectable in all control animals. Fetal cardiac bypass produced no significant changes in IL-1beta and IL-8 in either group. Following bypass, placental blood flow decreased by 23% in the bypass group, which was significantly more (P = 0.0002) than the 6% decrease in the control group; placental vascular resistance increased significantly more in the bypass group (20%) than in control fetuses (1%; p = 0.004).Conclusions: Fetal cardiac bypass produces significant and consistent increases in fetal plasma IL-6, which correlate with increased placental vascular resistance and decreased placental blood flow. IL-6 may have an important role in placental dysfunction following fetal cardiac bypass, but further investigation will be necessary to elucidate its specific role in the impairment of placental function or as a marker of placental injury.