Better preservation of endothelial function and decreased activation of the fetal renin-angiotensin pathway with the use of pulsatile flow during experimental fetal bypass

Abstract

Objective: Pulsatile flow was shown to overcome the progressive rise in peripheral and placental vascular resistances observed during steady-flow bypass, this rise being counteracted by inhibition of nitric oxide synthase. This study quantifies the release of endothelial vasoactive substances during a 60-minute in utero model of fetal bypass. Methods: Fetuses were randomly allocated into 1 of 2 groups (steady flow, n = 8, or pulsatile flow, n = 13) and subjected to bypass through central cannulation and perfusion with either a centrifugal or pulsatile (125 beats · min–1) blood pump. Results: Lactate concentration was high, starting at fetal exteriorization and increasing during fetal preparation in the 2 groups. Once bypass was established, the rise was significant only in the steady-flow group. Plasma nitric oxide metabolites, similar before bypass, reached higher levels during pulsatile flow at the end of bypass (99 ± 9 vs 82 ± 23 μmol · L–1; P = .037). Levels of urinary nitric oxide metabolites were significantly higher in the pulsatile-flow than in the steady-flow group (764 ± 143 vs 508 ± 240 μmol · L–1; P = .005). Plasma cyclic guanosine monophosphate levels increased after 30 minutes of bypass in the pulsatile-flow group (25 ± 18 vs 12 ± 8 pmol · mL–1; P = .004), and urinary cyclic guanosine monophosphate excretion was higher in the pulsatile-flow group (517 ± 450 vs 118 ± 78 pmol · mL–1; P = .024). Plasma endothelin-1 levels increased in the 2 groups and were higher in the steady-flow group at 30 minutes (27 ± 5 vs 23 ± 2 pg · mL–1; P = .04) and 60 minutes of bypass (39 ± 7 vs 32 ± 6 pg · mL–1; P = .04). Plasma renin concentration increased significantly during bypass only in the steady-flow group (26 ± 10 vs 57 ± 42 in ng A1 · mL–1 · h–1; P = .04). Conclusions: Improved placental and peripheral perfusion during fetal pulsatile-flow bypass may be mediated by preservation of fetal/maternal endothelial nitric oxide biosynthetic mechanisms and/or decreased activation of the fetal renin-angiotensin pathway. (J Thorac Cardiovasc Surg 2000;120:770-7)