Defective pulmonary development in the absence of heparin-binding vascular endothelial growth factor isoforms.

Development of the airways, alveoli, and the pulmonary vasculature in the fetus is a process that is precisely controlled. One of the growth factors involved, vascular endothelial growth factor (VEGF), is so critical for embryonic development that in the mouse, elimination of just a single allele is lethal. In the early stages of lung development, the mouse VEGF gene expresses three isoforms (120, 164, and 188) in a distinct temporo-spatial pattern, suggesting a specific function for each. We engineered mice that express only VEGF 120, to study the role of VEGF isoforms in lung development. Lung vessel development in these mice was studied by scanning electron microscopy of Mercox casts of lung vasculature. Airway and air-blood barrier development was analyzed by light microscopy, transmission electron microscopy, immunohistochemistry, and morphometry. In all VEGF120/120 fetuses and pups, lung vascular casts were smaller and less dense compared with 120/+ and wild-type littermates. Although the generation count of pre-acinar vessels was similar in all three genotypes, the most peripheral vessels were dilated and were more widely separated in 120/120 fetuses of all ages, compared with 120/+ and wild-type littermates. In addition, 120/120 animals had fewer air-blood barriers and a decreased airspace-parenchyma ratio compared with 120/+ and wild-type littermates. We concluded that the absence of VEGF 164 and 188 isoforms impairs lung microvascular development and delays airspace maturation, indicating an essential role for heparin-binding VEGF isoforms in normal lung development.

Iatrogenic acute hypermagnesemia after total parenteral nutrition infusion mimicking septic shock syndrome: two case reports.

Two premature newborn infants developed extreme magnesium toxicity while receiving total parenteral nutrition (TPN) infusion. Both patients exhibited acute hypotonia, apnea, hypotension, and refractory bradycardia mimicking septic shock syndrome. The complete blood count was normal, and blood cultures were negative. Serum magnesium concentration in 1 patient was 43.1 mEq/L and in the other patient was 45 mEq/L (normal values for serum magnesium being 1.6-2.1 mEq/L). Hypermagnesemia resulted from malfunction of an automated TPN mixing device. Unexplained sudden onset of apnea, refractory bradycardia, and hypotension should raise suspicions of hypermagnesemia, a reversible condition if identified and treated early.