Although cerebral hemorrhage is a widely occurring neurologic disorder thought to be caused by fluctuating blood flow, the response to flow in the neonatal cerebrovasculature has not been characterized. In the present study, we examined the effect of changing flow on middle cerebral artery diameter and pathways by which flow modulates cerebrovascular tone. Arteries from 2-14-d-old piglets were mounted on cannulas and bathed in and perfused with physiologic saline solution. An electronic system controlled pressure and a syringe pump provided constant flow. The transmural pressure was held constant at 20 mm Hg, and changes in vessel diameter were measured as flow was increased in steps from 0 to 1.60 mL/min (flow/diameter curves). Increasing flow at constant pressure resulted in constriction at flows from 0.077 to 0.152 mL/min and dilation at flows from 0.212 to 1.60 mL/min. The flow/diameter curves were repeated in arteries bathed in Na(+)-reduced or Ca(2+)-free physiologic saline solution; denervated with 6-hydroxydopamine; or treated with indomethacin, N-nitro-L-arginine methyl ester, N omega-nitro-L-arginine (NLA), and L-arginine), ryanodine, or glutaraldehyde. In Na(+)-reduced and in Ca(2+)-free physiologic saline solution, flow constriction was eliminated. Neither indomethacin nor 6-hydroxydopamine affected the biphasic response. N-Nitro-L-arginineL, NLA, and ryanodine blocked dilation, whereas L-arginine restored dilation in NLA-treated arteries. These data suggest that neither prostaglandins nor adrenergic nerve endings participate in flow-induced responses in piglet cerebral arteries. Elimination of flow-constriction by Na+ reduction or Ca2+ removal is consistent with findings in other artery types. The elimination of dilation by N-nitro-L-arginine methyl ester, NLA, and ryanodine suggests that dilation is mediated by nitric oxide and intracellular Ca2+. Whereas the contractile and dilatory responses to agonists remained intact after glutaraldehyde perfusion, both flow-induced constriction and dilation were eliminated, indicating that both types of flow responses result from endothelial cell deformation.

This study suggests tonsillectomy in NI children can be performed safely with appropriate monitoring and precautions with a 48-hour hospital postoperative stay recommended. Swallowing safety appears to improve both objectively and subjectively in most NI children following tonsillectomy. Both preoperative and postoperative VSS are recommended for any NI child undergoing tonsillectomy. Long-term follow-up identified improved quality of life measures for the majority of the NI children queried.

Isolated, cannulated, endothelium-intact cat pulmonary arteries, averaging 692 +/- 104 microns in diameter, were set at a transmural pressure of 10 mmHg and monitored with a video system. Intraluminal flow was increased in steps from 0 to 1.6 ml/min by using a syringe pump. An electronic system held pressure constant by changing outflow resistance. Flow-diameter curves were generated in physiological saline solution. At constant transmural pressure, the arteries constricted in response to increased intraluminal flow. Constriction was not affected by removing extracellular Ca2+ but was abolished after treatment with ryanodine to deplete intracellular Ca2+ stores, with the endothelin-1 synthesis inhibitor phosphoramidon, with the endothelin A-receptor antagonist BQ-123, with the protein kinase C inhibitor staurosporine, or with glutaraldehyde to reduce endothelial cell deformability. The results indicate that isolated pulmonary arteries can constrict in response to intraluminal flow and suggest that constriction is mediated by endothelin-1 and depends on intracellular Ca2+ release and protein kinase C activation.

Because cerebrovascular hemorrhage in newborns is often associated with fluctuations in cerebral blood flow, this study was designed to investigate the effects of pulsatile flow in isolated cerebral arteries from neonatal piglets. Arteries mounted on cannulas were bathed in and perfused with a physiologic saline solution. An electronic system produced pulsations, the amplitude and frequency of which were independently controlled. At constant mean transmural pressure (20 mm Hg), increasing flow in steps from 0 to 1.6 mL/min under steady flow conditions caused a biphasic response, constriction at low flow, and dilation at high flow. Under pulsatile flow conditions (pulse amplitude 16-24 mm Hg; 2 Hz), the arteries dilated upon flow initiation and continued to dilate as mean flow increased. Dilation to pulsatile flow did not depend on the level of mean flow because switching from steady to pulsatile flow at each flow step also caused dilation. Arteries dilated further upon increasing either pulse amplitude (12-28 mm Hg; 2 Hz) or frequency (16-24 mm Hg; 4 Hz). Inhibiting nitric oxide synthesis with Nomega-nitro-L-arginine or perfusing with glutaraldehyde to decrease endothelial cell deformability significantly reduced dilations to pulsatile flow and to increased amplitude and frequency. These data suggest that the arterial response to flow is highly dependent on the mode of flow. Dilation induced by initiating pulsatile flow or increasing either pulse amplitude or frequency appears to be mediated by augmented nitric oxide release as result of shear stress-induced deformation of the endothelial cells.

Supplemental iron as monotherapy or in combination with other treatments is effective in treating pediatric RLS. A prospective study could help determine if the initial ferritin level and degree of change in the ferritin level impact response to iron treatment. It is also important to study the long-term outcomes in these patients.