Control de la ventilación y regulación del estado ácido-base del pez al hombre / Control of ventilation and regulation of acid-base status from fish to man

RESUMEN Este artículo analiza ciertos aspectos evolutivos en el intercambio gaseoso, el desa rrollo pulmonar, la bomba respiratoria, el estado ácido-base y el control de la ventila ción en relación con un evento trascendente: el pasaje de la vida acuática a la terres tre. Su estudio puede permitir comprender ciertos aspectos con los que lidiamos en la práctica clínica: ¿Por qué las personas con debilidad muscular respiratoria extrema respiran como ranas (respiración frog)?, ¿Por qué los recién nacidos con dificultad respiratoria tienen aleteo nasal y quejido espiratorio?, ¿cómo es posible que los mús culos abdominales, típicamente espiratorios, asistan a la inspiración en casos de la parálisis diafragmática?, ¿por qué en la insuficiencia respiratoria el patrón respiratorio tiene menos variabilidad y se torna más rígido? y, por último, ¿es posible imaginar un pH neutro que no tenga el valor de 7,0, para qué sirve este conocimiento y como se deben interpretar los gases en hipotermia? La transición del agua a la tierra es una de las más importantes e inspiradoras de las grandes transiciones en la evolución de los vertebrados. Ante la sorprendente diversi dad de organismos vivos, es tentador imaginar una cantidad enorme de adaptaciones evolutivas para resolver los diferentes desafíos que cada especie tiene para la vida en la tierra. Hay desarrollos tempranos que comparten algunos factores cruciales y algunas de las redes genéticas regulatorias cercanas y lejanas están conservadas. Somos testigos de hallazgos clínicos que son el testimonio de especies que han vivido en épocas remotas y nos han legado su historia evolutiva.

ABSTRACT This article analyzes certain evolutionary aspects of gas exchange, lung development, the respiratory pump, the acid-base status and control of ventilation in relation to a significant event: the passing from aquatic to terrestrial life. By studying this, we can understand certain aspects that are present in the clinical practice: Why do people with extreme respiratory muscle weakness breathe as frogs? (frog breathing); why do newborns with breathing difficulties have nasal flaring and expiratory grunting?; how is it possible that abdominal muscles, which are typically expiratory, assist with inspira tion in cases of diaphragmatic paralysis?; why does the breathing pattern of respiratory failure has less variability and becomes more rigid? and, finally, is it possible to imagine a neutral pH that doesn't have the 7.0 value?; what's the use of this knowledge, and how should gases in hypothermia be interpreted? Water-to-land transition is one of the most important and inspiring major transitions of vertebrate evolution. Given the amazing diversity of living organisms, it is tempting to imagine an enormous amount of evolutionary adaptation processes to solve the different challenges of living on earth faced by each species. There are certain early development processes that share some crucial factors, and some of the close and distant gene regulatory networks are conserved. We are witnesses of clinical findings that serve as testimony of the species that lived in remote times and left us their evo lutionary history.

Central Hypoventilation Syndrome in Posterior Circulation Stroke Treated by Respiratory Rehabilitation: a Case Report

Central hypoventilation syndrome is a rare and fatal condition resulting from various central nervous system disorders that is characterized by a failure of automatic breathing. We report a case of central hypoventilation syndrome following posterior circulation stroke whose pulmonary function was improved by respiratory rehabilitation. A 59-year-old woman with a history of hemorrhagic stroke of the bilateral cerebellum was hospitalized due to pneumonia. A portable ventilator was applied via tracheostomy, recurrent episodes of apnea and hypercapnia impeded weaning. A respiratory rehabilitation program including chest wall range of motion exercise, air stacking exercise, neuromuscular electrical stimulation (NMES) on abdominal muscles, upper extremity ergometer, locomotor training, high-frequency chest wall oscillator, mechanical insufflation, and exsufflation was employed, as spirometry showed a severe restrictive pattern. A spontaneous breathing trial was started, and a portable ventilator was applied for 8 hours, only during nighttime, to prevent sudden apneic event. After 4 weeks of treatment, follow-up spirometry showed much improved respiratory parameters. This case suggests that respiratory rehabilitation can improve pulmonary function parameters and quality of life in central hypoventilation syndrome.

Role of GABAA receptors in sevoflurane-induced inhibition of discharge activities of inspiratory neurons in medullary respiratory center of neonatal rats / 中华麻醉学杂志

Objective To evaluate the role of GABAA receptors in sevoflurane-induced inhibition of the discharge activities of inspiratory neurons in the medullary respiratory center of neonatal rats.Methods The medulla oblongnta slices of neonatal rats (aged 0-4 days) including the medial region of the nucleus retrofacialis with the hypoglossal nerve rootlets retained were prepared.The slices were perfused with artificial cerebrospinal fluid (ACSF),and the activity of the inspiratory neurons in the medial region of the nucleus retrofacialis and the respiratory rhythmical discharge activity of the hypoglossal nerve rootlets were simultaneously recorded using microelectrodes and suction electrodes,respectively.The ACSF,5％ sevoflurane,GABAA receptor blocker bicuculline 10 μmol/L and combination of 5％ sevoflurane and 10 μmol/L bicuculline were added to the perfusion liquid after the discharge activity was stable.The respiratory cycle (RC),inspiratory time (TI),integral amplitude (IA) and changes in peak frequency (PFn) of the inspiratory neurons were recorded.Results Compared with that after giving ACSF,RC was significantly prolonged,TI was shortened,and IA and PFn were decreased after giving sevoflurane,and RC was significantly shortened,IA and PFn were increased (P＜0.05),and no significant change was found in TI after giving bicuculline (P＞ 0.05).Compared with that after giving sevoflurane,RC was significantly shortened,TI was prolonged,and IA and PFn were increased after giving sevoflurane and bicuculline (P＜ 0.05).Conclusion Sevoflurane inhibits the discharge activities of inspiratory neurons through GABAA receptors in the medullary respiratory center of neonatal rats.

The Relationship between Orexin A and Respiratory Drive in Patients with Chronic Obstructive Pulmonary Disease / 天津医药

Obejective To explore the correlation of Orexin A and respiratory drive in chronic obstructive pulmo-nary disease (COPD) patients. Methods Pulmonary function was tested in 30 stable COPD patients and 20 normal healthy adults. Plasma orexin A level was measured with a radioimmunoassay kit. The correlation of Orexin A with BMI, age, BDI, FEV1, FVC, FEV1/FVC, MEP, MIP, P0.1 in COPD patients was analyzed. Results Plasma Orexin A levels in patients with COPD group(1.87±0.43)ng/L was higher than those in the control group(1.49±0.19)ng/L, P<0.01. Plasma Orexin A lev-els in patients with COPD correlated negatively with FEV1(r=-0.389,P < 0.05),and correlated positively with P0.1(r=0.728,P<0.01). Conclusion Plasma orexin A in COPD patients increased which may be caused by smoking and hyper-capnia. Orexin A may play a crucial role in regulating respiratory drive in COPD patients.

The relationship between reduction of lung function and neural respiratory drive in healthy middle and aged subjects / 中华老年医学杂志

Objective To explore the relationship between reduction of lung function and neural respiratory drive in healthy middle and aged subjects. Methods Eight healthy middle and elderly subjects aged (57.3±5.0) years and 8 sex-matched healthy young subjects aged (28.3±3.4)years were enrolled iu this study. Conventional lung function tests were performed in all the subjects.Neural respiratory drive was assessed by electromyogram(EMG) recorded from a multipair esophageal electrode in quiescent condition and maximal forced inspiration. Results Maximal diaphragm EMG (EMGdi) at inspiration was similar between elderly and young subjects [(172.2 ± 54.66) μV vs.(175.0±55.7) μV,t -0.10,P=0.921] while vital capacity(VC) in the elderly subjects [(3.2±0.5)L] was much smaller than young subjects[(4.0±0.8)L](t=-2.27,P＜0.05).The tidal volume and ventilatory capacity per minute in quiescent condition in middle and aged people were similar to the youth,however,EMGdi％max was higher in the elderly subjects (27.8± 12.9)％ than in the young subjects (16.4±7.2)％ (t-2.18,P＜0.05).Effective drive of respiration center was much less in the elderly subjects than in young subjects [(62.7±23.2)％ vs.(128.6±96.2) ％].Conclusions Reserve of neural respiratory drive is less in the elderly than in young subjects.Decrease of lung function with ageing may be not due to reduction of neural respiratory drive but lung structure change.

Effect of doxapram on inhibition of medullary respiratory center excitability by sevoflurane in rats / 中华麻醉学杂志

Objective To investigate the effect of doxapram on inhibition of medullary respiratory center excitability by sevoflurane in rats.Methods Neonatal Sprague-Dawley rats of both sexes,aged 1-4 days,were used in this study.Isolated medulla oblongata-spinal cord specimens were made according to the method described by Suzue and perfused with the artificial cerebrospinal fluid saturated with 95％O2-5％CO2.The specimens were randomly divided into 3 groups ( n =9 each):control group (group C),sevoflurane group (group S) and sevoflurane + doxapram group (group S + D).Respiratory rhythmical discharge activity of the hypoglossal nerve rootlets was recorded using suction electrode.After 10 min of equilibration,the specimens were perfused with the artificial cerebrospinal fluid,5％ sevoflurane and the mixture of 5％ sevoflurane and 5 μmol/L doxapram for 10 min in groups C,S,and S + D respectively.The respiratory cycle,inspiratory time and integral amplitude of inspiratory discharge were recorded.Results Compared with group C,the respiratory cycle was significantly prolonged,the inspiratory time was significantly shortened,and the integral amplitude of inspiratory discharge was significantly decreased in group S (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group S + D (P ＞ 0.05).Compared with group S,the respiratory cycle was significantly shortened,the inspiratory time was significantly prolonged,the integral amplitude of inspiratory discharge was significantly increased in group S + D ( P ＜ 0.05).Conclusion Doxapram antagonizes sevoflurane-induced inhibition of excitability of medullary respiratory center in rats.

Role of reactive oxygen species in regulation of respiratory rhythm in medial area of nucleus retrofacialis / 第二军医大学学报

Objective: To explore the role of reactive oxygen species (ROS, i. e, H2O2 and O2-) in regulation of respiratory rhythm in the medial area of nucleus retrofacialis (mNRF). Methods: Medullary slices of neonatal SD rats, including hypoglossal nerve (XII n) and mNRF, were made according to Suzue's method. Simultaneous recording of the XII n respiratory rhythmic activity (RRA) with suction electrode and the respiratory neuronal discharge were performed with whole cell patch in the mNRF on the brainstem slice in vitro. The effect of t-butyl hydroperoxide (tBHP) and α-lipoic acid (α-LA) on the respiratory pacemaker neurons and respiratory rhythm in the mNRF were observed. Results: tBHP significantly decreased respiratory cycle (RC) and increased respiratory amplitude; α-LA significantly increased RC and decreased its amplitude. Meanwhile, α-LA significantly prolonged the action potential of the respiratory cadmium-insensitive pacemaker neurons and reduced its amplitude, but it had no significant effect on the cadmium-sensitive respiratory pacemaker neurons. Voltage steps and ramps showed that α-LA inhibited both the transient and persistent sodium current of cadmium-insensitive pacemaker neurons. Conclusion: ROS has an excitatory effect on the respiratory rhythm and the cadmium-insensitive respiratory pacemaker neurons through modulating sodium current.

Evolución clínica y de laboratorio en lactantes con inmadurez del centro respiratorio que presentan episodios de apnea

Resumen Los episodios de pausas respiratorias y de respiración periódica son normales en los lactantes, conformando un patrón de sueño normal con el crecimiento. El objetivo de este trabajo fue evaluar un grupo de lactantes con sospecha de apnea, en quienes se encontraron, mediante polisomnografía (PSG1), evidencias de inmadurez del centro respiratorio, indicándose educación en reanimación cardiopulmonar, monitor cardiorrespiratorio (MCRP) y control de polisomnografía (PSG2). Pacientes y método: se incluyeron 34 lactantes entre mayo 1997 y mayo 2001. Apnea fue definida como la ausencia de respiración por 20 segundos (central) y 10 segundos (obstructiva y mixta); pausas respiratorias como ausencia de respiración > 6 < 20 seg (central) y > 6 < 10 seg (obstructiva). Resultados: en todos se incluyó MCRP y se realizó un estudio inicial (PSG1) y final (PSG2); se evaluó las características de la PSG1 y se compara la evolución entre los 2 estudios. La muestra incluyó 22 hombres (65%), la edad promedio de la serie fue de 2,7 ± 2,3 meses ( ± DS), rango 0,3-9 meses. Los diagnósticos de referencia fueron apnea: (n = 27), RGE (n = 2) y cianosis (n = 4). Los eventos respiratorios promedio mostraron un índice total de pausas respiratorias de 14,1/hora, con predominio de centrales, y un porcentaje de respiración periódica de 4,5%. El examen fue anormal en 32 casos por presentar desaturación arterial (n = 23), apneas (n = 8), pausas centrales (n = 19), obstructivas (n = 9) y RGE patológico (n = 5). En relación al segundo examen (PSG2), la edad fue de 11,5 ± 4,5 (rango 6-24 meses). Al comparar PSG1 vs PSG2, hubo diferencias significativas en índice total de pausas (p < 0,01), pausas centrales (p < 0,05) y respiración periódica (p < 0,05). Se concluye que la mayoría de los pacientes con inmadurez del centro respiratorio normalizan sus parámetros al año de vida, y que en éstos es de utilidad un adecuado uso del monitor cardiorrespiratorio.

Summary Introduction: episodes of central pauses and periodic breathing are normal in infants and decrease with age and growth. Objective: to evaluate a group of infants that had a polysomnography (PSG) performed due to an episode of apnea, with elevated immature sleep characteristics and who required home cardiorespiratory monitoring (HCRM) and further control PSGs. Methods: 34 patients, 22 (65%) were male, mean age 27 ± 2 months (PSG1), range 0,3-9 years, were studied between May 1997 and May 2001. Along with the first PSG (PSG1) a second was performed (PSG2) prior to the suspension of HCRM. Apnea was defined as the absence of respiration for more than 20 sec (central) or more than 10 sec (obstructive and mixed); respiratory pauses as the absence of respiration for more than 6 sec and less than 20 sec (central) or more than 6 sec and less than 10 sec (obstructive). Results: the main indications for PSG were apnea (27 pts), cyanosis (4 pts) and gastro-oesophageal reflux (GER) in 2. Respiratory events showed mean respiratory pauses of 14.1/hr, mostly central and periodic breathing during 4,5% of the total sleep time (TST). PSG1 was abnormal in 32 cases, with desaturation in 23, apnea in 8, central pauses in 19, obstructive pauses in 9 and GER in 5. PSG2 was performed at a mean age of 11,5 ± 4 months, range 6-24 months. The comparision of PSG1 vs PSG2 showed significant differences in the total respiratory index (p < 0,01), central pauses (p < 0,05) and periodic breathing (p < 0,05), being always lower in the PSG2. We conclude that the majority of patients with episodes of apnea and immature sleep patterns normalized their sleep pattern in the first year of life. In this group the correct use of HCRM is indicated.

Catastrophic Respiratory Failure Associated with Unilateral PICA Infarction Involving Lateral Medullar Region

Medullar respiratory centers are composed of ventral and dorsal groups. A direct infarction to their structure could lead to a complete loss of respiratory drive, despite unilateral brainstem lesion is rarely associated with central respiratory dysfunction. A 70-year-old man was admitted with sudden dizziness and disequilibrium without motor weakness. Brain MRI (diffuse weight image) shows high signals intensities on left PICA territory of cerebellum and medulla oblongata including reticular formation, nucleus of tractus solitarius, nucleus ambiguus, and nucleus retroambiguus but sparing corticospinal and corticobulbar pathway. On 3rd hospital day, he had a complete loss of respiratory drive involving both autonomic and voluntary components. He didn't get the respiratory drive during CO2 retention while his consciousness and motor power were preserved.

Central Hypoventilation Syndrome during Awake and Sleep

Central hypoventilation syndrome (CHS) can be caused by any lesions to the medullary respiratory centers, cerebral cortex, corticospinal pathways, and their connections. We report 5 patients with central hypoventilation syndrome and analyzed 26 patients who experienced central hypoventilation syndrome during sleep and waking states. We compared initial clinical symptoms and signs, maximal neurologic deficits, brain MRI and pathologic findings, and associated autonomic dysfunctions. The patients with respiratory failure during waking states showed quadriplegia, a rapidly progressing respiratory failure. The patients who had automatic respiratory failure showed mild hemiparesis, bulbar dysfunction, dysautonomia, and subacute to chronic recurrent respiratory failures. These results support the concept of two separate respiratory systems: a voluntary system and an automatic system. The respiratory management of these patients with central hypoventilation syndrome should be considered critical to their survival.

Voluntary and Automatic Respiratory Failure after Unilateral Medullary Infarct: A Case Report

Medullary respiratory centers are composed of two respiratory groups: dorsal and ventral. A dorsal respiratory group consists primarily of inspiratory neurons. A ventral respiratory group consists both of inspiratory and expiratory neurons. A direct infarction of their structure may lead to a complete loss of respiratory drive involving both automatic and voluntary components. A 78-year-old man was admitted with sudden dysarthria, dizziness, and bilateral ophthalmoplegia. On the second and third hospital day, he nearly had a complete loss of respiratory drive involving both automatic and voluntary components. He did not get the respiratory drive during CO2 retention while consciousness and motor were preserved. Brain MRI showed unilateral lesions involving the medullary reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus but sparing the corticospinal tract. Unilateral medullary infarction may lead to severe respiratory failures not limited to automatic responses, which differentiates it from Ondine's curse.

Role of reactive oxygen species in regulation of respiratory rhythm in medial area of nucleus retrofacialis / 第二军医大学学报

Objective:To explore the role of reactive oxygen species(ROS,i.e,H_2O_2 and O_2-) in regulation of respiratory rhythm in the medial area of nucleus retrofacialis(mNRF).Methods: Medullary slices of neonatal SD rats,including hypoglossal nerve(Ⅻn) and mNRF,were made according to Suzue's method.Simultaneous recording of the Ⅻn respiratory rhythmic activity(RRA) with suction electrode and the respiratory neuronal discharge were performed with whole cell patch in the mNRF on the brainstem slice in vitro.The effect of t-butyl hydroperoxide(tBHP) and ?-lipoic acid(?-LA) on the respiratory pacemaker neurons and respiratory rhythm in the mNRF were observed.Results: tBHP significantly decreased respiratory cycle(RC) and increased respiratory amplitude;?-LA significantly increased RC and decreased its amplitude.Meanwhile,?-LA significantly prolonged the action potential of the respiratory cadmium-insensitive pacemaker neurons and reduced its amplitude,but it had no significant effect on the cadmium-sensitive respiratory pacemaker neurons.Voltage steps and ramps showed that ?-LA inhibited both the transient and persistent sodium current of cadmium-insensitive pacemaker neurons.Conclusion: ROS has an excitatory effect on the respiratory rhythm and the cadmium-insensitive respiratory pacemaker neurons through modulating sodium current.