Objective To investigate the brain injuries induced by intrauterine balloon aortic valvuloplasty (IUBAV) on a foetal lamb model, and to evaluate the effectiveness of protective therapies (feeding indometacin to pregnant goats) during the process of IUBAV scientificly and accurately.
Methods Thirty-two near term twin pregnant goats were randomly assigned to control group (Con Group: placebo to pregnant goat, n = 16) and indometacin group (Idm Group: indometacin to pregnant goat, n = 16). Based on whether adopting the indometacin and IUBAV, 64 foetal lambs were accordingly enrolled into four groups, which were Con-c (pregnant goat placebo + foetal lamb IUBAV control, n = 16), Con-o (pregnant goat placebo + foetal lamb IUBAV, n = 16), Idm-c (pregnant goat indomethacin + foetal lamb IUBAV control, n = 16) and Idm-o (pregnant goat indomethacin + foetal lamb IUBAV, n = 16). Ultrasound guided IUBAV model was established and different protective therapies were taken to different group according to the experimental protocol. The following parameters were dynamically monitored by ultrasound, which were foetal and neonatal heart rate (HR), cardiac rhythm, umbilical or/and aortic resistance index (RI) and pulsatility index (PI). On established IUBAV model, brain tissue specimens were taken from foetal/neonatal goats for hematoxylin-eosin (HE) staining, ultrastructural study of brain tissure, and TUNEL to detect neurons apoptosis.
Results After IUBAV, foetal umbilical RI, PI and aortic RI were increased, and there existed significant differences comparing pre-procedure (P < 0.05). Up to 3d-postprocedure, the values of RI and PI recovered to some extend, but statistical differences still were showed when comparing to pre-procedure (P < 0.05). After adopting indomethacin to pregnant goats, increased umbilica l/aortic RI and PI could be effectively suppressed. At the timepoints of pre, post, 3h-post and 3d-post IUBAV, foetal aortic PI were mild increased, but no statistical differences were showed (P < /span > >0.05). After oral administration indomethacin to pregnant goats, foetal aortic PI of each timepoint was stabled and no statistical differences were existed (P < /span > >0.05). There were no statistical differences of AorticRIand PI of newborns among each group (P > 0.05). Light microscopy detection of HE staining of brain tissue and electron microscopic ultrastructural examination of central neuron suggested that mild edoema appeared in the brain neurons and collagen fibres, mild edoema, vacuolization, endoplasmic reticulum degranulation phenomenon also occurred in various organelles. These aforementioned changes manifested relative obviously in foetal goats underwent IUBAV procedure. After adopting indomethacin to pregnant goats, these changes are alleviated to some extent.
Conclusions IUBAV could alter the dynamic state of foetal goat underwent IUBAV, which were showed as increased but reversible umbilical RI, PI and aortic RI. Protective therapy (indomethacin to pregnant goats) can significantly inhibit the increasing trends of RI and PI during and after the procedure, and stabled foetal dynamics during and after IUBAV. IUBAV could reversible ultrastructure lesion in central neurons and brain neuron sporadic apoptosis. Protective therapy (indomethacin to pregnant goats) could alleviate the degree of brain tissue lesions, and had a clear protective performance to foetal goats during and after foetal cardiac intervention.