Fetal in vivo continuous cardiovascular function during chronic hypoxia.

Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l(-1), P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species.This work was supported by the British Heart Foundation.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27109

Underwater Leidenfrost nanochemistry for creation of size-tailored zinc peroxide cancer nanotherapeutics

The dynamic underwater chemistry seen in nature is inspiring for the next generation of eco-friendly nanochemistry. In this context, green synthesis of size-tailored nanoparticles in a facile and scalable manner via a dynamic process is an interesting challenge. Simulating the volcano-induced dynamic chemistry of the deep ocean, here we demonstrate the Leidenfrost dynamic chemistry occurring in an underwater overheated confined zone as a new tool for customized creation of nanoclusters of zinc peroxide. The hydrodynamic nature of the phenomenon ensures eruption of the nanoclusters towards a much colder region, giving rise to growth of monodisperse, size-tailored nanoclusters. Such nanoparticles are investigated in terms of their cytotoxicity on suspension and adherent cells to prove their applicability as cancer nanotherapeutics. Our research can pave the way for employment of the dynamic green nanochemistry in facile, scalable fabrication of size-tailored nanoparticles for biomedical applications.Peer reviewe