RESUMO
We previously reported on the presence of respiratory pacemaker cells that are highly sensitive to CO(2), in a region of the medulla oblongata in the fetal rat, 2 mm rostral to the obex. We now report on the CO(2) 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% CO(2) for 2-3 weeks. Cells were then studied using patch-clamp techniques. Pacemaker cells with single or bursting potentials showed responsiveness to CO(2) starting with pulses of 10 msec. Irregular beating or silent cells had poor or absent responsiveness to CO(2). Pacemaker cells responded to norepinephrine with increased firing potential; this action was blocked by metropolol. PGE(2) had no effect on pacemaker-cell activity, but indomethacin increased the spike frequency from 336+/-41 to 384+/- 65 spikes/min. Morphine stimulated the pacemaker cells from 205+/-25 to 272+/-29 spikes/min; this was blocked by naloxone. Finally, a placental extract, which inhibited breathing in the unanesthetized fetal sheep preparation, increased the activity of pacemaker cells from 301+/-35 to 452+/-52 spikes/min. In all of the above, irregular beating cells responded poorly and silent cells did not respond. The findings indicate that these pacemaker cells are uniquely designed to respond to CO(2) and have some properties which allow them to respond to certain chemical mediators in a manner similar to that of the whole respiratory system in vivo.
Assuntos
Relógios Biológicos/efeitos dos fármacos , Dióxido de Carbono/farmacologia , Fenômenos Fisiológicos Respiratórios , Animais , Relógios Biológicos/fisiologia , Dióxido de Carbono/fisiologia , Células Cultivadas , Células Quimiorreceptoras/fisiologia , Relação Dose-Resposta a Droga , Bulbo/fisiologia , Morfina/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Neurotransmissores/fisiologiaRESUMO
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 L x min(-1) x 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) V(T)/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.
Assuntos
Envelhecimento/fisiologia , Recém-Nascido Prematuro , Ventilação Pulmonar/fisiologia , Respiração , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sono/fisiologiaRESUMO
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.
Assuntos
Obstrução das Vias Respiratórias/complicações , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/etiologia , Ventilação Pulmonar/fisiologia , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/etiologia , Idade Gestacional , Frequência Cardíaca , Humanos , Recém-Nascido , Fatores de TempoRESUMO
The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas the amplitude of the cardiac airflow oscillation remains nearly constant, in a subset of events the waveform decreases with time, suggesting airway narrowing. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during central apnea. To test this hypothesis we studied 41 preterm infants. Of 4,456 central apneas, 585 had a decrease in the amplitude of the cardiac oscillation. The amplitude of the cardiac airflow oscillation during an apnea was recorded to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 s intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using ANOVA. We found a significant decrease in cardiac airflow oscillation after only 1 s irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but appears shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation.
Assuntos
Apneia/fisiopatologia , Recém-Nascido Prematuro/fisiologia , Sistema Respiratório/fisiopatologia , Coração/fisiopatologia , Humanos , Recém-Nascido , Oscilometria , Ventilação Pulmonar/fisiologia , Fatores de TempoRESUMO
Paraplegia after an open heart operation in a neonate is a rare complication. We report a case of a infant in whom paraplegia developed after a successful arterial switch operation for transposition of the great arteries. The infant was monitored and resuscitated in the preoperative period with umbilical arterial and venous catheter tips located in the midthoracic region. He likely suffered a clinically silent thromboembolic event predisposing him to a localized hemorrhagic infarction during the repair.