Postnatal development of the Hering-Breuer reflex in the rat

The intensity of the Breuer-Hering inflation reflex was studied in newborn (1 day old), in young (8 days old) and in adult rats (90 days old) under urethane general anaesthesia (1.3 g/kg i.p.). The inflation pressure was adjusted with the aid of a water-valve. The reflex was present in all 3 age groups. An inflation pressure of 0.2 kPa applied in the course of expiration produced a long lasting apnoea in newborn rats which lasted 48 normal respiratory cycles. An inflation pressure of 0.5 kPa in young rats induced an apnoea lasting for only 3 normal respiratory cycles, whereas a pressure of 1 kPa in adult rats led to an apnoea which lasted for 20 normal respiratory cycles. The compliance of the respiratory system in relation to lung weight is approximately 5 times higher in adult rats compared with that of newborn rats. It is approximately double in comparison with young rats. The pressures of inflation mentioned in the 3 age categories can be considered as equieffective from the point of stimulation pulmonary stretch receptors. It can be concluded from these findings that the reflex of Breuer-Hering in newborn rats is more potent in comparison with adult rats, but it is lower in young rats at the age of 8 days. It is suggested that the differences observed are due to functional and anatomical maturation.     

Persistence of the Hering-Breuer reflex beyond the neonatal period

There is conflicting evidence regarding the persistence of the Hering-Breuer reflex (HBR) beyond the 1st wk of life. This study was designed to assess the influence of postnatal age on the HBR. The airway occlusion technique was used to assess changes in respiratory timing during stimulation of the HBR in healthy full-term unsedated infants measured shortly after birth and at 6-8 wk of life. The strength of the HBR was assessed from the relative change in expiratory time (TE) after end-inspiratory occlusion compared with resting TE during spontaneous breathing. Paired studies were performed in 31 infants at approximately 2 days and 6 wk of age. There was a significant increase in TE during each occlusion in every infant irrespective of age at measurement. No maturational changes were observed. The increase in TE after end-inspiratory occlusion was 91.9 +/- 31.6% (SD) (range 38-158%) at approximately 2 days and 89.8 +/- 30.7% (range 44-175%) at approximately 6 wk. We conclude that the activity of the HBR during tidal breathing persists beyond the neonatal period and that there is no statistically significant change in its strength during the first 2 mo life in healthy infants during natural sleep.     

Effects of lung congestion and oleic acid injury on the Hering-Breuer reflex

Breathing and the Hering-Breuer (HB) reflex may be stimulated by congestion and by acute lung injury, but there is disagreement about the effects of both stimuli. This study evaluated these effects using greater stimulus isolation and control of secondary interactions than have previously been employed. Pressurization of lung vessels and left heart and oleic acid injury were individually imposed on anesthetized open-chest dogs perfused with an external pump and gas exchanger. Lungs were inflated in steps before and during those stimuli. The HB reflex was evaluated from graphs of breathing frequency (fr) vs. airway pressure. Congestion itself had no significant sustained effect on fr, but it slightly depressed the HB reflex. Oleic acid tachypnea that was depressed to pretreatment fr by inflation, implying enhancement of the HB response. Capsaicin and oleic acid had similar effects. Vagal cooling to 8 degrees C slightly depressed the effects of oleic acid and capsaicin, had no effect on the sustained fr response to congestion, and reversed the inhibitory effect of inflation. A stimulation of breathing or an enhancement of the HB reflex by congestion was not confirmed, but oleic acid increased fr and the HB reflex.     

Volume of activation of the Hering-Breuer inflation reflex in the newborn infant.

Although the Hering-Breuer inflation reflex (HBIR) is active within tidal breathing range in the neonatal period, there is no information regarding whether a critical volume has to be exceeded before any effect can be observed. To explore this, effects of multiple airway occlusions on inspiratory and expiratory timing were measured throughout tidal breathing range using a face mask and shutter system. In 20 of the 22 healthy infants studied, there was significant shortening of inspiration because the volume at which occlusion occurred rose from functional residual capacity (FRC) to end-inspiratory volume [14.9% reduction in inspiratory time (per ml/kg increase in lung volume at occlusion)]. All infants showed a significant increase in expiratory time [17.1% increase (per ml/kg increase in lung volume at occlusion)]. Polynomial regression analyses revealed a progressive increase in strength of HBIR from FRC to approximately 4 ml/kg above FRC. Eighteen infants showed no further shortening of inspiratory time and 10 infants no further lengthening of expiratory time with increasing occlusion volumes, indicating maximal stimulation of the reflex had been achieved. There was a significant relationship between strength of HBIR and respiratory rate, suggesting that HBIR modifies the breathing pattern in the neonatal period.     

The Hering-Breuer reflex in anesthetized infants: end-inspiratory vs. end-expiratory occlusion technique

Bothend-inspiratory (EIO) and end-expiratory (EEO) occlusions have beenused to measure the strength of the Hering-Breuer inflation reflex(HBIR) in infants. The purpose of this study was to compare bothtechniques in anesthetized infants. In each infant, HBIR activity wascalculated as the relative prolongation of expiratory and inspiratorytime during EIO and EEO, respectively. Respiratory drive was assessedfrom the change in airway pressure during inspiratory effort againstthe occlusion, both at a fixed time interval of 100 ms(P_0.1) and a fixed proportion(10%) of the occluded inspiratory time(P_10%). Twenty-two infants [age 14.3 ± 6.4 (SD) mo] were studied. No HBIR activitywas present during EIO [11.8 ± 15.9 (SD) %]. Bycontrast, there was significant, albeit weak, reflex activity duringEEO [HBIR: 27.2 ± 17.4%]. A strong HBIR (up to 310%)was elicited in six of seven infants in whom EIO was repeated afterlung inflation. P_0.1 was similar during both types of occlusions, whereas mean ± SDP_10% was lower during EEO thanduring EIO: 0.198 ± 0.09 vs. 0.367 ± 0.15 kPa, respectively(P < 0.01). These data suggest adifference in the central integration of stretch receptor activity ininfants during anesthesia compared with during sleep.

     

Influence of volume dependency and timing of airway occlusions on the Hering-Breuer reflex in infants

Bothend-inspiratory (EIO) and end-expiratory (EEO) airway occlusions areused to calculate the strength of the Hering-Breuer inflation reflex(HBIR) in infants. However, the influence of the timing of suchocclusions is unknown, as is the extent to which changes in volumewithin and above the tidal range affect this reflex. The purpose ofthis study was to compare both techniques and to evaluate the volumedependency of the HBIR in healthy, sleeping infants up to 1 yr of age.The strength of the HBIR was expressed as the ratio of expiratory orinspiratory time during EIO or EEO, respectively, to that recordedduring spontaneous breathing, i.e., as the "inhibitory ratio"(IR). Paired measurements of the EIO and EEO in 26 naturally sleepingnewborn and 15 lightly sedated infants at ~1 yr showed nostatistically significant differences in the IR according to technique:mean (95% CI) of the difference (EIO  EEO) being0.02 (0.17, 0.13) during the first week of life and 0.04 (0.14, 0.22) at 1 yr. During tidalbreathing, a volume threshold of ~4 ml/kg was required to evoke theHBIR. Marked volume and age dependency were observed. In newborninfants, occlusions at ~10 ml/kg during sighs always resulted in anIR > 4, whereas a similar response was only evoked at 25 ml/kg inolder infants. Age-related changes in the volume threshold may reflectmaturational changes in the control of breathing and respiratorymechanics throughout the first year of life.

     

Hering-Breuer reflex in conscious newborn rats: effects of changes in ambient temperature during hypoxia.

In a previous study in conscious normoxic newborn rats, we found that the strength of the Hering-Breuer reflex (HB reflex) was greater (188%) at high (36 degrees C) than at low (24 degrees C) ambient temperature (T(a); D. Merazzi and J. P. Mortola. Pediatr. Res. 45: 370-376, 1999). We now asked what the effect would be of changes in T(a) during hypoxia. Rat pups at 3-4 days of age were studied in a double-chamber airflow plethysmograph. The HB reflex was induced by negative body surface pressures of 5 or 10 cmH(2)O and quantified from the inhibition of breathing during maintained lung inflation. Rats were first studied at T(a) = 32 degrees C in normoxia, followed by hypoxia (10% O(2) breathing). During hypoxia, oxygen consumption (VO(2)) averaged 47%, and HB reflex 115%, of the corresponding normoxic values, confirming that in the newborn, differently from the adult, hypoxia does not decrease the strength of the HB reflex. As hypoxia was maintained, lowering T(a) to 24 degrees C or increasing it to 36 degrees C, on average, had no significant effects on VO(2) and the HB reflex. However, with 5-cmH(2)O inflations, the HB reflex during the combined hypoxia and hyperthermia was significantly stronger than in normoxia. We conclude that in conscious newborn rats during normoxia the T(a) sensitivity of the HB reflex is largely mediated by the effects of T(a) on thermogenesis and VO(2); in hypoxia, because thermogenesis is depressed and VO(2) varies little with T(a), the HB reflex is T(a) independent. The observation that the reflex response to lung inflations during hypoxic hyperthermia can be greater than in normoxia may be of importance in the pathophysiology of apneas during the neonatal period.     

Circadian rhythms in the chemoreflex control of breathing

Mechanisms underlying the circadian rhythm in lung ventilation were investigated. Ten healthy male subjects were studied for 36 h using a constant routine protocol to minimize potentially confounding variables. Laboratory light, humidity, and temperature remained constant, subjects did not sleep, and their meals and activities were held to a strict schedule. Respiratory chemoreflex responses were measured every 3 h using an iso-oxic rebreathing technique incorporating prior hyperventilation. Subjects exhibited circadian rhythms in oral temperature and respiratory chemoreflex responses, but not in metabolic rate. Basal ventilation [i.e., at subthreshold end-tidal carbon dioxide partial pressure (PET(CO(2)))] did not vary with time of day, but the ventilatory response to suprathreshold PET(CO(2)) exhibited a rhythm amplitude of approximately 25%, mediated mainly by circadian variations in the CO(2) threshold for tidal volume. We conclude that the circadian rhythm in lung ventilation is not a simple consequence of circadian variations in arousal state and metabolic rate. By raising the chemoreflex threshold, the circadian timing system may increase the propensity for respiratory instability at night.     

电刺激家兔迷走神经中枢端诱导的黑-伯反射中的非联合型学习现象

本文旨在研究电刺激家兔迷走神经诱导的黑-伯（Hering-Breuer,HB）反射中的学习和记忆现象。选择性电刺激家兔迷走神经中枢端（频率10～100Hz,强度20～60μA,波宽0．3ms,持续60s）,观察对膈神经放电的影响。以不同频率电刺激家兔迷走神经可模拟HB反射的两种成分,即类似肺容积增大所致抑制吸气的肺扩张反射和类似肺容积缩小所致加强吸气的肺萎陷反射。（1）长时高频（≥40Hz,60s）电刺激迷走神经可模拟呼吸频率减慢,呼气时程延长的肺扩张反射。随着刺激时间的延长,膈神经放电抑制的程度逐渐衰减,表现为呼吸频率的减慢（主要由呼气时程延长所致）在刺激过程中逐渐减弱或消失,显示为适应性或“习惯化”的现象;刺激结束时呼吸运动呈现反跳性增强,表现为一过性的呼气时程缩短,呼吸频率加快,然后才逐渐恢复正常。长时低频（〈40Hz,60s）电刺激迷走神经可模拟呼吸频率加快、呼气时程缩短的肺萎陷反射。随着刺激时间的延长,膈神经放电增强的程度逐渐衰减,同样表现出“习惯化”现象;刺激结束后,膈神经放电不是突然降低,而是继续衰减,表现为呼气时程逐渐延长,呼吸频率逐渐减慢,直至恢复到前对照水平,表现了刺激后的短时增强效应。（2）HB反射的适应性或“习惯化”程度反向依赖于刺激强度和刺激频率,表现为随着刺激强度和频率的增加,膈神经放电越远离正常基线水平,即爿惯化程度减弱。结果表明,家兔HB反射具有“习惯化”这一非联合型学习现象,反映与其有关的呼吸神经元网络具有突触功能的可翅性,呼吸的中枢调控反射具有一定的适应性。