Aamir Hussain

A study of breathing pattern and ventilation in newborn infants and adult subjects

Experimentally modified breathing pattern in human subjects, by varying the inspired gas mixture or administering different neuromodulators, has been studied extensively in the past, yet unmodified breathing has not. Moreover, most data refer to infants during sleep and adults during wakefulness. We studied the baseline breathing pattern of preterm infants [n= 10; GA 30 (27–34) wk (median, range)]; term infants [n= 10; GA 40 (39–41) wk)], and adult subjects [n= 10; age 31 (17–48) y)] during quiet sleep. A flow‐through system was used to measure ventilation. We found: (i) instantaneous ventilation was 0.273 ± 0.006, 0.200 ± 0.003, and 0.135 ± 0.002 Lmin‐1.kg‐1 in preterm, term infants, and adult subjects; the coefficients of variation were 39%, 25%, and 14% (p <0.01). The greater coefficient of variation in neonates compared to adults related to increased variability in Vt (39% and 25% in preterm and term infants vs 14% in adults; p < 0.01) and f (39% and 22% vs 9%; p < 0.01). The major determinant of frequency in preterm infants was Te (81% variability), Ti varying less (25% variability); (ii) VT/Ti decreased and Ti/Ttot increased with age; (iii) the higher breath‐to‐breath variability in preterm infants was associated with larger changes in alveolar PCO2 and a larger variability in O2 saturation than later in life.

The morphology of periodic breathing in infants and adults

To test the hypothesis that the crescendo-decrescendo type of pattern of periodic breathing is more common in infants than in adulthood, we examined the morphologies of periodic breathing in four groups of subjects: group 1 (n=10, gestational age 30+/-1 week), group 2 (n=10, GA 31+/-1 week), group 3 (n=10, GA 38+/-1 week), and group 4 (n=10, age 50+/-4 years). Respiratory pattern and ventilation were measured using a flow-through system. The breathing morphologies were defined according to the respiratory flow. We found (1) a predominant crescendo-decrescendo pattern in preterm infants (groups 1 and 2, >50%) and this changed to a predominant decrescendo breathing in adults (group 4, 50%); (2) total breathing cycle and its phases did not change significantly among the neonatal groups, but they almost doubled in adult subjects; however, the number of breaths per breathing interval remained the same (crescendo-decrescendo) or less (flat and decrescendo) in adults as compared to preterm infants; (3) the duty cycle (breathing interval/cycle duration) remained consistent with age; and (4) at the beginning of each breathing interval, alveolar P(CO2) was highest and alveolar P(O2) and O2 saturation lowest. The findings suggest a change in the strategy of the respiratory control system during periodic breathing between the infant and the adult, perhaps dictated by mechanical and chemoreceptor limitations early in age, with a switch from a crescendo-decrescendo to a predominantly decrescendo pattern.

Respiratory pacemaker cells responsive to CO2 in the upper medulla: Dose response and effects of mediators

We previously reported on the presence of respiratory pacemaker cells that are highly sensitive to CO2, in a region of the medulla oblongata in the fetal rat, 2 mm rostral to the obex. We now report on the CO2 dose responses of these cells, as well as their responsiveness to certain chemical agents known to affect breathing in the fetus. Twenty‐day‐old fetal Sprague Dawley rats were block‐dissected, and the cells of target areas were dissociated as previously described. Neuronal cells were plated on a medullary background and placed in the incubator with 10% CO2 for 2–3 weeks. Cells were then studied using patch‐clamp techniques.

Physiologic Mechanisms Responsible for the Initiation of Periodic Breathing and Apnea in Preterm Infants ♦ 1674

Physiologic Mechanisms Responsible for the Initiation of Periodic Breathing and Apnea in Preterm Infants ♦ 1674

The Profile and Significance of Periodic Breathing in Preterm Infants.† 1517

Traditionally, periodic breathing in preterm infants has been considered benign, yet we have seen it frequently associated with more prolonged respiratory pauses. To examine the profile of periodic breathing during development we studied preterm and term infants at postconceptional ages 30±2 wk (weight 1.2±0.2 kg; n=9), 34±2 wk (weight 1.9±0.3 kg; n=8), 38±2 wk (weight 3.0±0.3 kg; n=8), and 42±2 wk (weight 4.2±0.4 kg; n=10). We hypothesized that the presence of periodic breathing is an ominous sign which correlates closely with increased prematurity, low oxygenation and prevalence of significant apnea (≥20 s). Respiratory pattern was measured using a flow-through system. Sleep state was monitored. We found 1) the prevalence of periodic breathing decreased from 25% to 22%, 21%, and 10% at 30, 34, 38, and 42 wk respectively; 2) this trend correlated closely with an increase in TcPO2 from 53±2 Torr at 30 wk to 70±2 Torr at 42 wk(p=0.01); the lowest saturation observed increased from 82% at 30 wk to 92% at 42 wk (p=0.02); 3) these changes were similar in quiet and REM sleep although the proportion of quiet sleep increased with age at the expense of REM sleep; 4) prevalence of apneas ≥20 s decreased from 28% at 30 wk to 12% at 34 wk, and to 0% thereafter (p=0.005); the longest apnea decreased from 42 to 35, 14, and 11 seconds at 30, 34, 38, and 42 wk of postconceptional age, respectively, and 5) the breathing cycle decreased from 17±1 seconds at 30 wk to 15±1 seconds at 42 wk of gestation (p=0.01); this was due primarily to a decrease in the breathing interval, apnea length remaining unchanged. The findings indicate a very significant link between prematurity, low oxygenation, periodic breathing and significant apnea, which appears to be independent of sleep state. We conclude that periodic breathing of prematurity is indeed an ominous sign and represents the initial instability of the respiratory control system necessary to generate pathologic apneas.Supported by the Childrens Hospital of Winnipeg Research Foundation.

Periodic Breathing (BP) in Small Infants (≤1500g): Ventilatory Correlates and Significance. 1450

Periodic Breathing (BP) in Small Infants (≤1500g): Ventilatory Correlates and Significance. 1450

Airway Closure During Mixed Apneas in Preterm Infants: Is Respiratory Effort Necessary? |[bull]| 1800

Airway closure during mixed apneas in preterm infants may be due to lack of tone in the upper airway followed by collapse and obstruction or diaphragmatic action inducing obstruction. We examine whether respiratory efforts are necessary for airway closure using a new method of detecting airway obstruction, based on the disappearance of an amplified cardiac pulse observed on the respiratory flow tracing. We analyzed 198 episodes of mixed apnea of various lengths (> or = 3 seconds) observed in 33 preterm infants (birth weight, 1.4 +/- 0.1 kg [mean +/- SEM]; study weight, 1.7 +/- 0.1 kg; gestational age, 29 +/- 1 weeks; post-natal age, 33 +/- 4 days). The great majority of these episodes (88%) had a central, followed by an obstructive, component. Infants were studied by using a nosepiece and a flow-through system. Respiratory efforts (abdominal and chest movements) were recorded. Of the apneas, 20 were < 5 seconds; 78, 5 to < 10 seconds; 45, 10 to < 15 seconds; 27, 15 to < 20 seconds; and 28, > or = 20 seconds. Of the 198 mixed apneas, 151 (76%) occurred in the absence of any respiratory effort; 43 (22%) showed a simultaneous cessation of the cardiac oscillation and respiratory effort; and 4 (2%) showed diaphragmatic activity appearing after cessation of the cardiac oscillation (airway occlusion). Respiratory efforts never preceded the cessation of the cardiac oscillation. The findings suggest that diaphragmatic action is not needed to occlude the airway in mixed apneas. The simultaneous cessation of cardiac oscillations (airway occlusion) and onset of respiratory efforts may indicate that such effort contributes to closure or is induced by the same stimulus that closes the airway. We speculate that the mechanism for airway closure in mixed apneas is most likely a lack of upper airway tone, which normally occurs with the cessation of a central drive to breathe.

Physiologic Mechanisms Likely Responsible for the Termination of Apnea in Preterm Infants ♦ 1676

To examine the mechanisms responsible for the termination of apnea in preterm infants, we analyzed the polygraphic records of 35 infants [BW 1200±112 g (Mean±SE); SW 1400±136 g; GA 29±1 wk; PNA 29±4 d] studied in our apnea lab over the last 5 years. Of 2572 apneas, 391 apneas (15%) were ≥ 10 s and 62 (2.4%) ≥ 20 s. Pulmonary resistance increased 57% (1.1±0.1 to 1.7±0.3 cmH2O·L·-1·min-1) from the breath just preceding apnea to the breath just following apnea, and increased with the duration of apnea (p=0.01). Narrowing or obstruction of the airway was reflected by breaths in-phase (no chest distortion; 85%) before apnea and out-of-phase (distortion; 96%) after apnea. Sighs, reflecting a strong chemical drive, occurred during the first 2-3 breaths following apnea and were more frequent in long apneas (40% vs 22% in short apneas; p<0.001). Movements were also more common during long apneas (31%; 122/391) than during short apneas (6%; 135/2181; p<0.001). Sighs and movements were more common in apneas with bradycardia (50%) than in those without bradycardia (32%; p<0.01) and in apneas with desaturation <85% (44%) than in those without desaturation (28%; p<0.001). Of 62 apneas longer than 20 s, 12 followed an episode of periodic breathing, resembling “a pause -following- a pause”, each consisting of a respiratory pause followed by an ineffective respiratory effort and a subsequent pause. Coinciding with this ineffective respiratory effort, bradycardia and desaturation became pronounced, further impairing the reinitiation of breathing. In the remaining prolonged apneas, chemical drive was unable to induce a respiratory effort. We suggest: 1) the mechanism responsible for prolonged apneas consists frequently of a failure of an ineffective chemical drive to overcome the high pulmonary resistance at the end of apnea; 2) bradycardia and desaturation further impair the cardiorespiratory system, perpetuating the respiratory pause; and 3) sighs and movements are factors aimed at breaking the respiratory pause. We speculate that the termination of apnea is a balance between the strength of the chemical drive and the increased airway resistance related to a partial or completely collapsed airway at the end of apnea.

Charaterization of Pacemaker Cells Uniquely Responsive to CO 2 : Effects of Neuromediators and a Placental Extract ♦ 1731

Charaterization of Pacemaker Cells Uniquely Responsive to CO 2 : Effects of Neuromediators and a Placental Extract ♦ 1731

Pure Obstructive Apneas in Preterm Infants: Where are They? 1538

According to the traditional classification an obstructive apnea is defined by absence of respiratory flow and presence of respiratory efforts. However, when we examined these apneas according to the presence or absence of the magnified cardiac oscillation signal (Lemke et al, Pediatr. Res., 37:340A, 1995), it became clear that these obstructive apneas were actually mixed, with the intermittent presence of the cardiac oscillation signal on the respiratory flow. We have therefore hypothesized that purely obstructive apneas are non-existent and that what used to be called obstructive by the traditional method were indeed mixed apneas. To test this hypothesis we examine 1931 apneas ≥ 3 seconds in 15 infants (birthweight 1200±114g; study weight 1400±136g; gestational age 29±1 wk; postnatal age 29±4 d). We used a flow-through system to measure respiratory pattern. Of the 1931 apneas, 1481 (77%) were central and 450 (23%) were mixed by the cardiac oscillation method; 285 (15%) were ≥ 10 seconds and 55 (3%) were longer than 20 seconds. No obstructive apneas were observed. However, of the mixed apneas, 11% would have been classified as obstructive by the previous method, because there were sporadic respiratory efforts present in the absence of respiratory flow. These were clearly interspersed with periods of airway opening and presence of cardiac oscillations. These findings suggest that when apneas are measured with a more accurate index of airway obstruction, ie., absence of a magnified cardiac oscillation signal, obstructive apneas are non-existent. We conclude that in preterm infants apneas should be defined as central or mixed only and speculate that the primary mechanism responsible for all apneas is central.Supported by the Childrens Hospital of Winnipeg Research Foundation.