Papers by Philip J Berger
Frontiers in Pediatrics
Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 milli... more Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insuf...
The Journal of Physiology, 1996
and attenuation of sound in the isolated fetal lung as it is expanded
Annals of the American Thoracic Society, 2014
Patients with obstructive sleep apnea (OSA) experience respiratory events with greater frequency ... more Patients with obstructive sleep apnea (OSA) experience respiratory events with greater frequency and severity while in the supine sleeping position. Postural modification devices (PMDs) prevent supine sleep, although there is a paucity of guidance to help clinicians decide when to use PMDs for their patients. In order for PMDs to treat OSA effectively, patients must experience respiratory events in the supine sleeping position consistently from night to night and must have a low nonsupine apnea and hypopnea index (AHINS). To document the repeatability of traditionally defined supine predominant OSA on consecutive polysomnography, to determine whether the consistency of the supine-predominant phenotype can be improved by altering the definition of it, and to determine whether a low AHINS is repeatable from night to night. We recruited 75 patients for polysomnography on two separate nights. Patients were classified as having supine OSA on each night on the basis of traditional and nov...
American Zoologist, 1987
SYNOPSIS. Anatomical evidence for the existence of a depressor nerve in reptiles was first report... more SYNOPSIS. Anatomical evidence for the existence of a depressor nerve in reptiles was first reported 100 years ago. Electrical stimulation of the central end of the cut nerve, however, did not produce an unequivocal fall in heart rate and blood pressure, so it was thought not to function as a depressor nerve. This remained the state of knowledge for fifty years when Marco Fedele performed a superb anatomical and physiological study of the depressor nerves of turtles and lizards. He demonstrated that there were two depressor nerves from each vagus; the superior nerve originated from the jugular ganglion or superior laryngeal nerve in turtles and from the superior laryngeal nerve or vagus in lizards; the inferior nerve originated from the nodose ganglion or slightly caudad of this ganglion. The nerves were shown to terminate in the proximal truncus arteriosus. Unlike the earlier workers, Fedele obtained a clear depressor effect on stimulating the depressor nerves. In more recent times baroreflexes have been demonstrated in response to hemorrhage and body tilting in reptiles, with snakes receiving particular attention. The evidence indicates that aquatic snakes are less effective at maintaining blood pressure than terrestrial and arboreal forms. The sensitivity (gain) of the baroreceptor-heart rate reflex, when it is expressed as a percentage change in heart rate per unit pressure change, is approximately the same in reptiles, amphibians, and mammals. In addition, the ultrastructural appearance of the baroreceptors of lizards is similar to that of mammals. A quantitative assessment of the ability of reptiles to correct disturbances in blood pressure has not yet been made, but techniques for obtaining this information are now available.
To examine the relation between increased newborn oxygen requirements and the postnatal rise in c... more To examine the relation between increased newborn oxygen requirements and the postnatal rise in cardiac output, we measured left ventricular (LV) output, organ blood flows, and whole-body oxygen consumption using radioactive microspheres in late-gestation sheep fetuses and in the same animals 1 and 4 hours after cesarean section delivery. LV output rose from 264±23 ml * min` kg body wt-' in fetuses to 444±33 ml * min`. kg body wt-' in lambs at 1 hour after delivery (p<0.005) and was unchanged at 4 hours after delivery. This rise in LV output was associated with a more than fourfold increase in the LV flow contribution to tissues situated distal to the ductus arteriosus (fetus, 51+9 ml * min -̀ kg body wt-V; lamb, 226+22 ml * min`-* kg body wt-V; p<0.005), which were mainly perfused by the right ventricle in utero. However, average blood flow to body tissues was similar in fetuses (37+4 ml * min`100 g tissue-'), 1-hour lambs (39+4 ml * min`. 100 g tissue-'), and...
Journal of Applied Physiology, 1999
Fetal lung liquid volume is usually determined by using radio-iodinated serum albumin (RISA) or b... more Fetal lung liquid volume is usually determined by using radio-iodinated serum albumin (RISA) or blue dextran (BD) as volume tracers. We tested the reliability of both tracers at 124 (G124) and 142 days of gestation (G142; term = G147) when the labels were employed simultaneously. We measured the proportion of label bound reversibly to the lung, or apparently lost from the lung compartment, by washing out the lung with saline and 5% albumin. At G124, volume estimates with the two labels were similar. At G142, the volume estimate with BD (36.3 ± 8.7 ml/kg of body wt) was higher ( P < 0.05) than with RISA (22.3 ± 3.5 ml/kg). This difference resulted from reversible binding of BD, because 5% albumin washout released 38.5 ± 4.0% of the BD added at the start of the experiment but a lesser amount of RISA (9.8 ± 0.7%; P < 0.05). At G142, when RISA was used alone, its reversible binding was 1.3 ± 0.2%. Background absorbance increased during experiments, giving rise to an apparent incre...
Journal of cellular and molecular medicine, Jun 13, 2016
Bronchopulmonary dysplasia (BPD) is a severe lung disease of preterm infants, which is characteri... more Bronchopulmonary dysplasia (BPD) is a severe lung disease of preterm infants, which is characterized by fewer, enlarged alveoli and increased inflammation. BPD has grave consequences for affected infants, but no effective and safe therapy exists. We previously showed that prophylactic treatment with interleukin-1 receptor antagonist (IL-1Ra) prevents murine BPD induced by perinatal inflammation and hyperoxia. Here, we used the same BPD model to assess whether an alternative anti-inflammatory agent, protein C (PC), is as effective as IL-1Ra against BPD. We also tested whether delayed administration or a higher dose of IL-1Ra affects its ability to ameliorate BPD and investigated aspects of drug safety. Pups were reared in room air (21% O2 ) or hyperoxia (65% or 85% O2 ) and received daily injections with vehicle, 1200 IU/kg PC, 10 mg/kg IL-1Ra (early or late onset) or 100 mg/kg IL-1Ra. After 3 or 28 days, lung and brain histology were assessed and pulmonary cytokines were analysed us...
Journal of Applied Physiology, 2015
Systemic maternal inflammation is implicated in preterm birth and bronchopulmonary dysplasia (BPD... more Systemic maternal inflammation is implicated in preterm birth and bronchopulmonary dysplasia (BPD) and may induce morbidities including reduced pulmonary function, sleep-disordered breathing, and cardiovascular disorders. Here we test the hypothesis that antenatal maternal inflammation per se causes altered alveolar development and increased chemoreflex sensitivity that persists beyond infancy. Pregnant C57BL/6 mice were administered lipopolysaccharide (LPS) (150 μg/kg ip) to induce maternal inflammation or saline (SHAM) at embryonic day 16 (randomized). Pups were weighed daily. On days 7, 28, and 60 (D07, D28, and D60), unrestrained wholebody plethysmography quantified ventilation and chemoreflex responses to hypoxia (10%), hypercapnia (7%), and asphyxia (hypoxic hypercapnia). Lungs were harvested to quantify alveolar number, size, and septal thickness. LPS pups had reduced baseline ventilation per unit bodyweight (∼40%, P < 0.001) vs. SHAM. LPS increased ventilatory responses t...
Archives of Disease in Childhood, 2014
necessary. In 21/82 cases INSURE was not successful. In the unsuccessful group patients were not ... more necessary. In 21/82 cases INSURE was not successful. In the unsuccessful group patients were not significantly younger and smaller. Procalcitonin levels at the age of one day were significantly higher the group of unsuccessful cases. III-IV Gr. IVH occurred in 6/82 necrotizing enterocolitis in 7/82 and bronchopulmonary dysplasia in 7/82 cases. Complications were more frequent in those cases whose INSURE therapy was unsuccessful. Conclusions The introduction of INSURE-therapy grossly decreased the need for invasive respiratory support. High procalcitonin levels and clinical manifestations of early neonatal infections as well as low birth weight negatively influenced the success of INSURE-therapy.
Archives of Disease in Childhood, 2014
necessary. In 21/82 cases INSURE was not successful. In the unsuccessful group patients were not ... more necessary. In 21/82 cases INSURE was not successful. In the unsuccessful group patients were not significantly younger and smaller. Procalcitonin levels at the age of one day were significantly higher the group of unsuccessful cases. III-IV Gr. IVH occurred in 6/82 necrotizing enterocolitis in 7/82 and bronchopulmonary dysplasia in 7/82 cases. Complications were more frequent in those cases whose INSURE therapy was unsuccessful. Conclusions The introduction of INSURE-therapy grossly decreased the need for invasive respiratory support. High procalcitonin levels and clinical manifestations of early neonatal infections as well as low birth weight negatively influenced the success of INSURE-therapy.
Archives of Disease in Childhood, 2012
The Aim of this study is to evaluate the lung function of babies who were born under birth weight... more The Aim of this study is to evaluate the lung function of babies who were born under birth weight of 1500 grams using impulse oscillometry in preschool age. Eighty-six children who were 3-6 years old and followed in our neonatology clinic (born under birth weight of 1500 grams) were enrolled in the study as the patient group and 40 term-born healthy children as the control group. The demographic data of the patients, duration of mechanical ventilation and oxygen therapy and presence of BPD were recorded. After routine physical examination, lung functions of the patients were measured by impulse oscillometry. The data were evaluated by SPSS 16 program. Forty-nine (57%) of 86 patients were non-BPD, 20 were mild BPD, 14 were moderate BPD and 3 were severe BPD. Weight and height of pramature and control groups were similar. There was a statistically significant difference between the two groups in terms of resistance (R5, R10, R20), reactance (X5, X10, X20) and resonant frequency (fres). The airway resistance was significantly higher and reactance was significantly lower in the premature group. However, there was no difference between BPD and non-BPD groups. In conclusion; although premature babies can catch-up their peers at 3-4 years old in terms of their body percentiles, their lungs still reflect the traces of prematurity.
The Journal of Physiology, 1997
1. Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body ... more 1. Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body activity, and yet earlier experiments in neonates have shown that PB incidence may be increased following the application of hyperoxia. To clarify this paradox, we studied the changes in the pattern of PB that occur following administration of oxygen in a lamb model of PB. 2. PB was induced in eleven of seventeen anaesthetized lambs following passive hyperventilation with air. When oxygen was administered during PB, the pattern was first enhanced, as evidenced by a sudden decrease in the ratio of the ventilatory duration to the apnoeic pause duration, and then suppressed, as evidenced by a progressive return to stable breathing which was associated with an increase in minute ventilation. 3. Five of the six lambs that did not show PB following passive hyperventilation with air could be made to do so if oxygen was substituted for air as the inspired gas following passive hyperventilation. 4. Five of the eleven lambs that showed PB following hyperventilation with air responded to the application of oxygen during PB by switching to a gross form of episodic breathing consisting of long apnoeic pauses followed by equally long periods of breathing during which minute ventilation fell progressively with time. 5. We conclude that when applied against a background of arterial hypoxaemia, oxygen has a destabilizing influence on ventilation in that (a) it accentuates the unstable breathing that occurs during PB, (b) it induces PB in lambs that exhibited stable breathing in air, and (c) it may precipitate episodic breathing.
PLoS Computational Biology, 2009
Rapid arterial O 2 desaturation during apnea in the preterm infant has obvious clinical implicati... more Rapid arterial O 2 desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O 2 desaturation during apnea (_ S Sa O2) is complicated by the non-linear O 2 dissociation curve, falling pulmonary O 2 uptake, and by the fact that O 2 desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O 2 consumption accelerates _ S Sa O2 throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar P O2 causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates _ S Sa O2 during stage 1, and finally, total blood O 2 capacity (blood volume and hemoglobin content) alone determines _ S Sa O2 during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia.
Journal of Applied Physiology, 2009
Limited evidence suggests that the ventilatory interaction between O2 and CO2 is additive after b... more Limited evidence suggests that the ventilatory interaction between O2 and CO2 is additive after birth and becomes multiplicative with postnatal development. Such a switch may be linked to the propensity for periodic breathing (PB) in infancy. To test this idea, we characterized the maturation of the respiratory controller and its effect on breathing stability in ∼10-day-old lambs and 6-mo-old sheep. We measured 1) carotid body sensitivity via dynamic ventilatory responses to step changes in O2 and CO2, 2) steady-state ventilatory sensitivity to CO2 under hypoxic and hyperoxic conditions, 3) the dependence of the apneic threshold on arterial Po2, and 4) the effect of hypoxic or hypercapnic gas inhalation during induced PB. Stability of the system was assessed using surrogate measures of loop gain. Peripheral sensitivity to O2 was higher in newborn than in older animals ( P < 0.05), but peripheral CO2 sensitivity was unchanged. Central CO2 sensitivity was reduced with age, but the ...
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Papers by Philip J Berger