Brief perinatal hypoxia increases severity of pulmonary hypertension after reexposure to hypoxia in infant rats

Abstract

We hypothesized that disrupted alveolarization and lung vascular growth caused by brief perinatal hypoxia would predispose infant rats to higher risk for developing pulmonary hypertension when reexposed to hypoxia. Pregnant rats were exposed to 11% inspired oxygen fraction (barometric pressure, 410 mmHg; inspired oxygen pressure, 76 mmHg) for 3 days before birth and were maintained in hypoxia for 3 days after birth. Control rats were born and raised in room air. At 2 wk of age, rats from both groups were exposed to hypoxia for 1 wk or kept in room air. We found that brief perinatal hypoxia resulted in a greater increase in right ventricular systolic pressure and higher ratio of right ventricle to left ventricle plus septum weights after reexposure to hypoxia after 2 wk of age. Moreover, perinatal hypoxic rats had decreased radial alveolar counts and reduced pulmonary artery density. We conclude that brief perinatal hypoxia increases the severity of pulmonary hypertension when rats are reexposed to hypoxia. We speculate that disrupted alveolarization and lung vascular growth following brief perinatal hypoxia may increase the risk for severe pulmonary hypertension with exposure to adverse stimuli later in life.

Obstructive sleep apnea and cardiovascular risk in children

“…Более того, весьма вероятно, что воздействие на ребенка интеркуррентной гипоксии, связанной с апноэ сна, может модифицировать реактивность легочных сосудов в последующие возрастные пери-оды, делая взрослых более предрасположенными к формированию легочной гипертензии [41]. Исследования свидетельствуют о том, что об-структивное апноэ сна у детей сопровождается си-стемной воспалительной реакцией [42].…”

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

“…Perinatal hypoxia increases risk of late pulmonary hypertension. Left, brief perinatal exposure to hypoxia increases susceptibility to PAH after late exposure to hypoxia in rats (RVSP: right ventricular systolic pressure; NN: normoxic control; NH: perinatal normoxia, postnatal hypoxia; HH: perinatal and postnatal hypoxia; HN: perinatal hypoxia, postnatal normoxia; NS: not significant; *P < 0.05 vs. NH; # P < 0.05 vs. NN); reproduced with permission from Figures 3 and 7 of Tang et al 145 Right, young adults with a history of neonatal distress and persistent pulmonary hypertension of the newborn have marked acute hypoxic pulmonary vasoreactivity response at altitude in humans; reproduced with permission from Sartori et al 146 adulthood. 12 Similarly, perinatal hypoxia increases susceptibility to late PAH after brief reexposure to hypoxia during adulthood (Figure 8, left).…”

Fluorescent microangiography (FMA): an improved tool to visualize the pulmonary microvasculature

“…[9][10][11][12][13][14] However, in addition to the drawbacks of histological sectioning, the high viscosity of the barium mixture (as much as 100-300 centipoise) necessitates the use of an artificially high perfusion pressure resulting in distension of the proximal vasculature. In contrast, our technique uses an agarose mixture with a viscosity similar to that reported for the relative blood viscosity in the microvasculature (less then 5 centipoise at 371C); 15 and the optimal perfusion pressure for this mixture was found to be at 40 mmHg.…”