In this review, the maturational changes occurring in the mammalian respiratory network from fetal to adult ages are analyzed. Most of the data presented were obtained on rodents using in vitro approaches. In gestational day 18 (E18) fetuses, this network functions but is not yet able to sustain a stable respiratory activity, and most of the neonatal modulatory processes are not yet efficient. Respiratory motoneurons undergo relatively little cell death, and even if not yet fully mature at E18, they are capable of firing sustained bursts of potentials. Endogenous serotonin exerts a potent facilitation on the network and appears to be necessary for the respiratory rhythm to be expressed. In E20 fetuses and neonates, the respiratory activity has become quite stable. Inhibitory processes are not yet necessary for respiratory rhythmogenesis, and the rostral ventrolateral medulla (RVLM) contains inspiratory bursting pacemaker neurons that seem to constitute the kernel of the network. The activity of the network depends on CO2 and pH levels, via cholinergic relays, as well as being modulated at both the RVLM and motoneuronal levels by endogenous serotonin, substance P, and catecholamine mechanisms. In adults, the inhibitory processes become more important, but the RVLM is still a crucial area. The neonatal modulatory processes are likely to continue during adulthood, but they are difficult to investigate in vivo. In conclusion, 1) serotonin, which greatly facilitates the activity of the respiratory network at all developmental ages, may at least partly define its maturation; 2) the RVLM bursting pacemaker neurons may be the kernel of the network from E20 to adulthood, but their existence and their role in vivo need to be further confirmed in both neonatal and adult mammals.

Maturation of the Mammalian Respiratory System

Early clamping of the umbilical cord at birth, a practice developed without adequate evidence, causes neonatal blood volume to vary 25% to 40%. Such a massive change occurs at no other time in one's life without serious consequences, even death. Early cord clamping may impede a successful transition and contribute to hypovolemic and hypoxic damage in vulnerable newborns. The authors present a model for neonatal transition based on and driven by adequate blood volume rather than by respiratory effort to demonstrate how neonatal transition most likely occurs at a normal physiologic birth.

Neonatal transitional physiology: a new paradigm.

Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth that contributes significantly to morbidity and mortality in neonatal intensive care units. BPD results from life-saving interventions, such as mechanical ventilation and oxygen supplementation used to manage preterm infants with acute respiratory failure, which may be complicated by pulmonary infection. The pathogenic pathways driving BPD are not well-delineated but include disturbances to the coordinated action of gene expression, cell-cell communication, physical forces, and cell interactions with the extracellular matrix (ECM), which together guide normal lung development. Efforts to further delineate these pathways have been assisted by the use of animal models of BPD, which rely on infection, injurious mechanical ventilation, or oxygen supplementation, where histopathological features of BPD can be mimicked. Notable among these are perturbations to ECM structures, namely, the organization of the elastin and collagen networks in the developing lung. Dysregulated collagen deposition and disturbed elastin fiber organization are pathological hallmarks of clinical and experimental BPD. Strides have been made in understanding the disturbances to ECM production in the developing lung, but much still remains to be discovered about how ECM maturation and turnover are dysregulated in aberrantly developing lungs. This review aims to inform the reader about the state-of-the-art concerning the ECM in BPD, to highlight the gaps in our knowledge and current controversies, and to suggest directions for future work in this exciting and complex area of lung development (patho)biology.

/pdf/the-extracellular-matrix-in-bronchopulmonary-dysplasia-114mzqv7ow.pdf

The Extracellular Matrix in Bronchopulmonary Dysplasia: Target and Source

Respiratory disease syndrome (RDS) is a condition of neonatal calves in which insufficient oxygen uptake and increased retention of carbon dioxide result in respiratory acidosis. This condition is more common in premature calves and seems to be associated with a deficiency of surfactant. Although there is no uniform definition of RDS, clinical signs appear as tachypnea and expiration accentuated by an abdominal lift and expiratory grunt, and they occur in association with characteristic blood gas changes. This article discusses the pathophysiology of RDS in calves, along with the clinical findings, diagnosis, and treatment options.

https://www.vetfood.theclinics.com/article/S0749-0720(08)00088-1/pdf

Respiratory distress syndrome in calves.

Neonatal maternal separation and early life programming of the hypoxic ventilatory response in rats.

The factors which regulate the transition to lung gas exchange in the newborn are not well understood. The transition begins within seconds of birth with the newborn's first breath and is largely complete by 30 min of age at which time breathing is continuous, and arterial blood gas tensions and pH approach stable newborn values. Experiments indicate that sensory stimulation caused by cutaneous cooling or sciatic nerve stimulation can result in the initiation of breathing within seconds. Thus, massive sensory stimulation of the newborn caused by labour and delivery probably plays an important role in promoting the rapid onset of lung ventilation. Any delay in the onset of lung gas exchange causes a rise in arterial PCO2 and fall in pH which would stimulate breathing probably via stimulation of the central chemoreceptors. Since an impairment of CO2 elimination is usually observed after birth, a rise in arterial PCO2 likely stimulates breathing in the newborn. However, this impairment is transient and is usually corrected within 30 min to 2 h of age. Recent experiments suggest that placental perfusion inhibits the fetal central respiratory system and that this effect may be mediated by a placentally-produced respiratory inhibitor. Thus, withdrawal of a respiratory inhibitor from the circulation may play an important role in maintaining breathing in the newborn after sensory stimulation wanes and arterial PCO2 returns to normal fetal levels.

Adamson Sl

Papers

Regulation of breathing at birth.