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Infants dying with bronchopulmonary dysplasia (BPD) demonstrate increased numbers of pulmonary neuroendocrine cells (PNEC). These infants also possess altered airway epithelial and smooth muscle dimensions reminiscent of oxygen-exposed animals. Because the pathogenesis of BPD involves oxygen toxicity, we hypothesized that chronic hyperoxia would induce both airway remodeling and PNEC hyperplasia. To test this theory, we compared the small airway morphology of 21-d-old rats subsequently exposed to 2 wk of >95% O2(Ox; n = 12) with that of normoxic controls (Con;n = 12). In paraffin-embedded sections, airways <1500 µm cut in cross-section were analyzed using light microscopy and image analysis software. The degree of epithelial and smooth muscle hyperplasia was assessed with proliferating cell nuclear antigen (PCNA). PNEC content was assessed via immunohistochemical staining for calcitonin gene-related peptide (CGRP) and the number of solitary PNEC (PNECsol) and PNEC clusters(neuroepithelial bodies, NEB) counted per section. We found that oxygen exposure increased epithelial and smooth muscle wall thickness (epithelium: Con, 12.3 ± 1.4 versus Ox, 14.8 ± 1.4 µm,p < 0.05; smooth muscle: Con, 7.0 ± 1.0 versus Ox, 10.0 ± 1.0 µm, p < 0.05). The changes in wall dimensions were accompanied by a 20% increase in fractional PCNA labeling of the epithelium but not the smooth muscle. Both PNECsoland NEB number increased in the Ox group (PNECsolCon, 3.6 ± 2.6versus Ox, 6.3 ± 3.1/100 mm epithelium, p < 0.05; NEB Con, 7.1 ± 4.0 versus 11.9 ± 3.6/100 mm epithelium, p < 0.05). These findings document an association between hyperoxia, airway remodeling, and PNEC hyperplasia and imply that PNEC products may contribute to the pathogenesis of oxygen-related pulmonary diseases such as BPD.

This study evaluated vascular function and growth of the forearm in nine children (mean age 9.2 years) who had undergone left subclavian flap aortoplasty for the infantile type of coarctation of the aorta many years (mean 9.0) earlier. Variables used to investigate bilateral forearm vascular function included forearm blood flow and resistance measured by strain gauge plethysmography under rest conditions, in response to 30 s of static handgrip exercise at 40% maximal voluntary contraction and in response to 10 min of forearm arterial occlusion (that is, the reactive hyperemic blood flow response). Forearm growth was ascertained by measuring right and left forearm volumes, lengths, circumferences and skinfold thicknesses.

In an effort to determine whether chronic physical forearm activity would increase both structural and physiologic indices of peripheral forearm vasodilation, we studied a group (N= 7) of individuals chronically performing high levels of arm work, young wheelchair-confined paraplegics, and compared them with ten young, able bodied control subjects. The index of vasodilator capacity was the flow response following the release of 10 min of arterial occlusion, the peak reactive hyperemic blood flow response (RHBF). The index of a structural effect of training on the vasculature was the brachial artery diameter (cm) derived by simultaneous measurement of velocity and forearm blood flow (area = flow·forearm volume·velocity−1). Vascular function differed significantly between the groups, with a greater RHBF (paraplegics, 53.8 ± 3.7; controls, 38.2 ± 1.5 ml·min−1·100 ml−1; P< 0.05) and a larger brachial artery diameter at rest (paraplegics, 0.4 ± 0.01 vs controls, 0.3 ± 0.02 cm; P< 0.05) in the paraplegics. We conclude that chronic upper extremity activity leads to an enhanced capability to vasodilate resistance vessels acutely and to a structural dilation of large conductance vessels.