Vasa vasorum hypoperfusion is responsible for medial hypoxia and anatomic remodeling in the newborn lamb ductus arteriosus

This is a non-final version of an article published in final form in KAJINO, HIROKI ; GOLDBARG, SETH ; ROMAN, CHRISTINE ; LIU, BAO MEI ; MAURAY, FRANÇOISE ; CHEN, YAO QI ; TAKAHASHI, YASUSHI ; KOCH, CAMERON J. ; CLYMAN, RONALD I., Vasa vasorum hypoperfusion is responsible for medial hypoxia and anatomic remodeling in the newborn lamb ductus arteriosus, Pediatric research 51(2), 2002 FEB, pp. 228-235. AuthorPostnatal constriction of the full-term ductus arteriosus produces hypoxia of the muscle media. This is associated with anatomic remodeling (including smooth muscle death) that prevents subsequent reopening. We used late-gestation fetal and neonatal lambs to determine which factors are responsible for the postnatal hypoxia. Hypoxia [measured by 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide technique] and cell death (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique) were observed in regions of the constricted ductus wall within 4 h after delivery. Although there was a decrease in ductus luminal flow during the first 6 h after delivery (measured by Doppler transducer), the amount of oxygen delivered to the ductus lumen (3070 ± 1880 μmol O_2 · min^ · g^) far exceeded the amount of oxygen consumed by the constricted ductus (0.052 ± 0.021 μmol O2 · min^ · g^, measured in vitro). Postnatal constriction increased the effective oxygen diffusion distance across the ductus wall to >3× the limit that can be tolerated for normal tissue homeostasis. This was owing to both an increase in the thickness of the ductus (fetus, 1.12 ± 0.20 mm; newborn, 1.60 ± 0.17 mm;p · g^; newborn, 0.21 ± 0.08 mL · min^ · g^;p < 0.01). These findings suggest that hypoxic cell death in the full-term ductus is caused primarily by changes in vasa vasorum flow and muscle media thickness and can occur before luminal flow has been eliminated. We speculate that in contrast with the full-term ductus, the preterm ductus is much less likely to develop the degree of hypoxia needed for vessel remodeling inasmuch as it only is capable of increasing its oxygen diffusion distance to 1.3× the maximally tolerated limit

Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers.

Objective:The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion.Design:Randomized, single-blind crossover design.Subjects:Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4).Intervention:Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment I3g) or 9 g (treatment I9g) fat (safflower oil).Measurements:Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY.Results:C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g (I3g and I9g) significantly increased satiety during and after fat perfusion, without differences in satiety between I3g and I9g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels.Conclusion:Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.International Journal of Obesity advance online publication, 16 September 2008; doi:10.1038/ijo.2008.166