Reflex control of expiratory duration in newborn infants

We investigated the effect on expiratory duration (TE) of application of graded resistive and elastic loads and total airway occlusions to single expirations in 9 full-term healthy infants studied on the 2nd or 3rd day of life. The infants breathed through a face mask and pneumotachograph, and flow, volume, airway pressure, and diaphragm electromyogram (EMG) were recorded. Loads were applied to the expiratory outlet of a two-way respiratory valve using a manifold system. Application of all loads resulted in expired volumes (VE) decreased from control (P less than 0.05), and changes were progressive with increasing loads. As VE became smaller, end-expiratory volume (EEV) became greater. TE, measured either from the pattern of airflow or airway pressure, or from diaphragm EMG activity, progressively increased with increasing loads and was greatest with total occlusions (P less than 0.05, compared with control). Resistive loading resulted in a greater accumulated VE history than elastic loading to the same EEV. For equivalent changes in EEV, TE was more prolonged with resistive than with elastic loading. Expiratory loading did not change the inspiratory duration determined from the diaphragm EMG activity of the breath immediately following each loaded expiration. These findings in infants are consistent with an integrative neural mechanism that modulates TE in response to the accumulated VE history, including both EEV and rate of lung deflation.     

Control of inspiratory duration in premature infants

We used single-breath mechanical loads and airway occlusions in premature infants to determine whether maturation influences the reflex control of inspiratory duration. We measured flow, volume, airway pressure, and surface diaphragmatic electromyogram (EMG) in 10 healthy preterm infants [33 +/- 1 (SD) wk gestation], 2-7 days of age. Three resistive and two elastic loads and occlusions were applied to the inspiratory outlet of a two-way respiratory valve. Application of all loads resulted in inspired volumes significantly decreased from control (P less than 0.001), and these decreases were progressive with increasing loads. Inspiratory duration (TI) was prolonged from control by all loads and occlusions when measured from the diaphragmatic EMG (neural TI) and by all but the smaller elastic load when measured from the flow tracing (mechanical TI). Similar decreases in inspired volume at the end of neural TI produced by application of both elastic and resistive loads resulted in comparable prolongation of neural TI. In contrast, for comparable volume decrements, resistive loading prolonged mechanical TI more than elastic loading (P less than 0.001). Mechanical and neural TI values of the breath after the loaded breath were unchanged from control values. Comparison of the neural volume-timing relationship in premature infants with our data in full-term infants suggests that the strength of the timing response to similar relative decrements in inspired volume is comparable. We conclude that reflex control of neural TI in premature infants depends on the magnitude of inspired volume and is independent of the volume trajectory.(ABSTRACT TRUNCATED AT 250 WORDS)     

On the relation between expiratory duration and subsequent inspiratory duration

To characterize respiratory interphase relationships in dogs, inspiratory duration (TI) or expiratory duration (TE) was systematically altered by electrical activation of vagal afferents, and the effect on subsequent TE or TI values was measured from the phrenic discharge. A linear TI-subsequent TE relationship was found. Following a vagally mediated prolongation of TE, 1) TI was prolonged, and the TE-subsequent TI relationship was curvilinear, 2) the threshold for inspiratory termination by phasic vagal inputs was increased, 3) the amplitude of the time course of the phrenic discharge was reduced so that the peak discharge reached the same level at inspiratory termination independent of TI, 4) the effect on TI prolongation persisted for several breaths whereas the effect was minimal on subsequent TE values, and 5) for tonic inputs the direct shortening of TI was nearly offset by the indirect lengthening of TI. These studies suggest the existence of slow central mechanisms that provide adaptation to elevated levels of vagal input in the control of TI. These mechanisms may also be responsible for the interphase timing relationships.     

A chronobiological study on the relation between heart rate and QT interval duration in newborn infants

The relation between heart rate and QT interval is the result of the autonomic nervous system control on cardiac function in healthy adults; accordingly, chronobiological studies have shown that adult subjects have circadian rhythms of heart rate (expressed as R-R interval) and QT interval in phase. We have employed chronobiological methods to study heart rate and QT interval relation in 10 newborn infants, who are known to have an immature cardiac control. Findings from this study indicate that not all the newborns show circadian rhythms of heart rate and QT interval and that when both rhythms are present they do not correlate like in the adults. Likely, this lack of relationship between heart rate and QT interval in newborns is due to different maturational stages of the newborns studied. As a practical implication, in newborn infants, mathematical correction of QT interval by heart rate is not a reliable method.     

Microbiological control of drug resistance of causative agents in suppurative-septic infections in newborn infants

Resistance of the main causative agents of purulent septic infections such as pneumonia, meningitis, sepsis, etc. to 11 chemotherapeutic drugs was studied. The pathogens were isolated from autopsies of 203 newborns who died within 1981 to 1987. Among 2978 isolates belonging to Enterobacteriaceae (2466 strains) and Pseudomonadaceae (512 strains) which constituted 88% of all the isolates, strains with multiple resistance predominated: 90% of the strains resistant to 4 or more antibiotics, 77% of the strains resistant to 6 or more antibiotics and 48% of the strains resistant to 8 or more antibiotics. The highest number of the isolates were resistant to 8 and 9 chemotherapeutics (19 and 20%, respectively). 84% of all the isolates belonged to 4 genera: Klebsiella (34%), Escherichia (21%), Serratia (14%) and Pseudomonas (15%). They were characterized by the highest resistance spectra. In all the cases massive colonization of the intestine by the strains with multiple resistance which caused purulent septic infections was observed. The most frequent variants of the drug resistance combination were determined. In the total frequency of the isolate with multiple resistance no significant differences were detected in 1981 and thereafter. In 1986-1987 the frequency of S. marcescens strains increased 3-5 times with simultaneous broadening of their drug resistance spectra. Strains of S. marcescens and K. pneumoniae with multiple drug resistance endemic for definite hospitals were detected.     

Head measurements in newborn infants

Normal anthropometric standards for head length and head width expressed in absolute and index values were determined in 366 newborn infants born between 28 and 42 gestational weeks. Mean +/- 2 SD values are tabulated separately according to gestational age or birth weight. The findings suggest that breech presentation and cesarean section alone do not significantly influence the anthropometric indices of the head in the otherwise normal neonate.     

Breath-by-breath interactions between inspiratory and expiratory duration in occlusive sleep apnea

We examined interactions between inspiratory duration (TI), expiratory duration (TE), and inspiratory (esophageal) pressure (Pes) generation in seven subjects with confirmed occlusive sleep apnea. Breath-by-breath values of TI, TE, and Pes were identified by digital computer during 21 260-s epochs of repetitive occlusive apnea during non-rapid-eye-movement sleep. The control theory of interacting nonlinear oscillators was used to categorize the interaction between TI and TE for each epoch as either 1) synchronization, the strongest possible interaction between biological oscillators; 2) relative entrainment, a moderate interaction between oscillators; or 3) relative coordination, a weak interaction. The latter two interactions were characterized by systemic oscillations in the moving cross-correlation between TI and TE. The relationship between TI and Pes was analyzed in a similar fashion. Significant oscillations were present in all three parameters (P less than 0.0001 for each). We observed significant negative correlations between TI and TE and between TI and Pes (P less than 0.001 for each) when all breaths for all epochs were pooled. In no epoch was there a significant positive correlation between TI and TE or Pes. All three interactions were observed between TI and TE: five epochs of synchronization, nine of relative entrainment, and seven of relative coordination. In contrast, 19 of 21 epochs exhibited synchronization between TI and Pes, with 2 epochs of relative entrainment. The relative frequency of TI vs. Pes synchronization was significantly greater than TI vs. TE synchronization (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimation of gluconeogenesis in newborn infants

The rate of glucose turnover (R(a)) and gluconeogenesis (GNG) via pyruvate were quantified in seven full-term healthy babies between 24 and 48 h after birth and in twelve low-birth-weight infants on days 3 and 4 by use of [(13)C(6)]glucose and (2)H(2)O. The preterm babies were receiving parenteral alimentation of either glucose or glucose plus amino acid with or without lipids. The contribution of GNG to glucose production was measured by the appearance of (2)H on C-6 of glucose. Glucose R(a) in full-term babies was 30 +/- 1.7 (SD) micromol. kg(-1). min(-1). GNG via pyruvate contributed approximately 31% to glucose R(a). In preterm babies, the contribution of GNG to endogenous glucose R(a) was variable (range 6-60%). The highest contribution was in infants receiving low rates of exogenous glucose infusion. In an additional group of infants of normal and diabetic mothers, lactate turnover and its incorporation into glucose were measured within 4-24 h of birth by use of [(13)C(3)]lactate tracer. The rate of lactate turnover was 38 micromol. kg(-1). min(-1), and lactate C, not corrected for loss of tracer in the tricarboxylic acid cycle, contributed approximately 18% to glucose C. Lactate and glucose kinetics were similar in infants that were small for their gestational age and in normal infants or infants of diabetic mothers. These data show that gluconeogenesis is evident soon after birth in the newborn infant and that, even after a brief fast (5 h), GNG via pyruvate makes a significant contribution to glucose production in healthy full-term infants. These data may have important implications for the nutritional support of the healthy and sick newborn infant.     

Metabolism of threonine in newborn infants

Threonine kinetics, threonine oxidative pathway, and the relationship between threonine and whole body protein turnover were quantified in 10 healthy term infants during the first 48 h after birth. The kinetic data were obtained 6 h after the last feed (fasting) and in response to formula feeding, using [U-(13)C(4),(15)N]threonine, [(2)H(5)]phenylalanine, and [(15)N]glycine tracers. The rate of carbon dioxide production (Vco(2)) and (13)C enrichment of the expired CO(2) were measured to quantify the rate of oxidation of threonine. The rate of appearance (R(a)) of threonine (136 +/- 37 micromol.kg(-1).h(-1)) was higher in newborn infants than that reported in adults. Formula feeding resulted in a significant decrease in threonine R(a) (P < 0.05). A significant positive correlation was seen between phenylalanine R(a) and threonine R(a), both during fasting and after formula feeding (r(2) = 0.65). In contrast to a 1:1 ratio of threonine and phenylalanine in mixed muscle protein, threonine R(a) relative to phenylalanine R(a) was 2.2 +/- 0.4. The fractional rate of threonine flux oxidized was 20% during fasting and 26% (P < 0.05) in response to nutrient administration. There was a significant correlation between plasma threonine concentration and threonine oxidation (r(2) = 0.75). No measurable incorporation of threonine in plasma glycine was seen. These data suggest that threonine is exclusively degraded by the glycine-independent serine/threonine dehydratase pathway. A higher flux of threonine relative to phenylalanine indicates higher turnover of threonine enriched proteins.