Apnea of prematurity (AOP) is frequently managed with nasal continuous positive airway pressure (NCPAP). Nasal cannula (NC) are used at low flows (<0.5 L/min) to deliver supplemental oxygen to neonates. A number of centers use high-flow nasal cannula (HFNC) in the management of AOP without measuring the positive distending pressure (PDP) generated. Objective. To determine the NC flow required to generate PDP equal to that provided by NCPAP at 6 cm H(2)O and to assess the effectiveness of HFNC as compared NCPAP in the management of AOP. Method. Forty premature infants, gestation 28.7 +/- 0.4 weeks (mean +/- standard error of mean), postconceptual age at study 30.3 +/- 0.6 weeks, birth weight 1256 +/- 66 g, study weight 1260 +/- 63 g who were being managed with conventional NCPAP for at least 24 hours for clinically significant apnea of prematurity, were enrolled in a trial of ventilator-generated conventional NCPAP versus infant NC at flows of up to 2.5 L/min. End expiratory esophageal pressure was measured on NCPAP and on NC, and the gas flow on NC was adjusted to generate an end expiratory esophageal pressure equal to that measured on NCPAP. Two 6-hour periods were continuously recorded and the data were stored on computer. Results. The flow required to generate a comparable PDP with NC varied with the infant's weight and was represented by the equation: flow (L/min) = 0.92 + 0.68x, x = weight in kg, R = 0.72. There was no difference in the frequency and duration of apnea, bradycardia or desaturation per recording between the 2 systems. Conclusion. NC at flows of 1 to 2.5 L/min can deliver PDP in premature neonates. HFNC is as effective as NCPAP in the management of AOP.

In this overview, we outline what is known regarding the key developmental stages of phrenic nerve and diaphragm formation in perinatal rats. These developmental events include the following. Cervical axons emerge from the spinal cord during embryonic (E) day 11. At approximately E12.5, phrenic and brachial axons from the cervical segments merge at the brachial plexi. Subsequently, the two populations diverge as phrenic axons continue to grow ventrally toward the diaphragmatic primordium and brachial axons turn laterally to grow into the limb bud. A few pioneer axons extend ahead of the majority of the phrenic axonal population and migrate along a well-defined track toward the primordial diaphragm, which they reach by E13.5. The primordial diaphragmatic muscle arises from the pleuroperitoneal fold, a triangular protrusion of the body wall composed of the fusion of the primordial pleuroperitoneal and pleuropericardial tissues. The phrenic nerve initiates branching within the diaphragm at approximately E14, when myoblasts in the region of contact with the phrenic nerve begin to fuse and form distinct primary myotubes. As the nerve migrates through the various sectors of the diaphragm, myoblasts along the nerve's path begin to fuse and form additional myotubes. The phrenic nerve intramuscular branching and concomitant diaphragmatic myotube formation continue to progress up until E17, at which time the mature pattern of innervation and muscle architecture are approximated. E17 is also the time of the commencement of inspiratory drive transmission to phrenic motoneurons (PMNs) and the arrival of phrenic afferents to the motoneuron pool. During the period spanning from E17 to birth (gestation period of approximately 21 days), there is dramatic change in PMN morphology as the dendritic branching is rearranged into the rostrocaudal bundling characteristic of mature PMNs. This period is also a time of significant changes in PMN passive membrane properties, action-potential characteristics, and firing properties.

The goal of this study was to determine when fetal breathing movements (FBMs) commence in the rat and to characterize age-dependent changes of FBMs in utero. These data provide a frame of reference for parallel in vitro studies of the cellular, synaptic, and network properties of the perinatal rat respiratory system. Ultrasound recordings were made from unanesthetized Sprague-Dawley rats from embryonic (E) day 15 (E15) to E20. Furthermore, the effects of respiratory stimulants (doxapram and aminophylline) and hypoxia on FBMs were studied. Single FBMs, occurring at a very low frequency (approximately 8 FBMs/h), commenced at E16. The incidence of single FBMs increased to approximately 80 FBMs/h by E20. Episodes of clustered rhythmic FBMs were first observed at E18 (approximately 40 FBMs/h). The incidence of episodic clustered FBMs increased to approximately 300 FMBs/h by E20, with the duration of each episode ranging from approximately 40 to 180 s. Doxapram, presumably acting to stimulate carotid body receptors, did not increase FBMs until E20, when the incidence of episodic clustered FBMs increased twofold. Aminophylline, a central-acting stimulant, caused an increase in episodic clustered FBMs after E17, reaching significance at E20 (3-fold increase). Exposing the dam to 10% O(2) caused a rapid, marked suppression of FBMs (5-fold decrease) that was readily reversed on exposure to room air.

The goals of this study were to further our understanding of diaphragm embryogenesis and the pathogenesis of congenital diaphragmatic hernia (CDH). Past work suggests that the pleuroperitoneal fold (PPF) is the primary source of diaphragmatic musculature. Furthermore, defects associated with an animal model of CDH can be traced back to the formation of the PPF. This study was designed to elucidate the anatomic structure of the PPF and to determine which regions of the PPF malform in the well-established nitrofen model of CDH. This was achieved by producing three-dimensional renderings constructed from serial transverse sections of control and nitrofen-exposed rats at embryonic day 13.5. Renderings of left- and right-sided defects demonstrated that the malformations were always limited to the dorsolateral portions of the caudal regions of the PPF. These data provide an explanation of why the holes in diaphragmatic musculature associated with CDH are characteristically located in dorsolateral regions. Moreover, these data provide further evidence against the widely stated hypothesis that a failure of pleuroperitoneal canal closure underlies the pathogenesis of nitrofen-induced CDH.