Moving Time Average Research Articles

The carotid body in the motorneuron response to protriptyline

Protriptyline (PRT) has been shown to preferentially stimulate upper airway inspiratory motorneurons relative to phrenic activity in hyperoxic hypercapnia in the decerebrate cat via a carotid body-independent mechanism. Since previous studies indicated that carotid body stimulation results in preferential activation of upper airway respiratory muscles during both hypercapnia and hypoxemia, we hypothesized that if PRT preferentially stimulated upper airway motorneurons, the mechanism of action might involve the carotid body. We investigated the effect of PRT on carotid body function by comparing the electrical activity of the hypoglossal (HYP) with that of the phrenic (PHR) nerve in carotid sinus nerve intact (CSNI) and CSN-sectioned (CSNX) anesthetized rats, before and after PRT (0.5 mg/kg i.v.), during 100% O 2, 15% O 2(N 2 balance), and 4% CO 2(O 2 balance) administration. The moving time average (MTA) peak inspiratory electroneurogram activities of both the HYP and PHR nerves increased an equivalent amount after PRT injection during hyperoxia, in both CSNI and CSNX rats. During hypoxia, the HYP activity increased significantly more than the PHR activity only in CSNI rats after PRT injection. During hyperoxic hypercapnia, HYP MTAs increased a similar amount in the CSNI and CSNX rats. We conclude that the HYP and PHR respiratory motorneutron pool responses to PRT depend on the blood gas status at the time of drug administration.

Comparisons among external resistive loading, drug-induced bronchospasm, and dense gas breathing in cats: roles of vagal and spinal afferents.

In anesthetized cats, breathing spontaneously, increase in lung resistance (RL) was induced by either external resistive loads (ERL) or internal loading produced by dense gas breathing (sulfur hexafluoride, SF6) or serotonin (5-HT)-induced bronchoconstriction. The 3 test agents were used in each animal. Arterial blood gases were maintained in the normal range. Ventilatory and cardiovascular responses were studied in 3 groups of animals: intact, vagotomized, or spinalized at C8 level, a condition that preserved diaphragmatic afferents. In intact or spinal animals, ERL as well as SF6 inhalation lengthened the inspiratory and/or the expiratory periods, whereas 5-HT injections elicited rapid shallow breathing. The changes in ventilatory timing with either type of load were not observed in vagotomized cats. In all animals, ERL breathing or 5-HT injections increased the moving-time average of diaphragmatic EMG measured at constant time (Edi 0.1 and 0.5 secs), but this was not observed during SF6 inhalation, a condition in which the magnitude of RL increase was less than in the 2 other situations. The changes in systemic arterial blood pressure and/or cardiac frequency were mostly associated with 5 HT-induced bronchoconstriction. They persisted in spinalized cats, but were not observed or reversed in vagotomized ones. These observations demonstrate that vagal afferents play a major role in the changes in ventilatory timing and cardiovascular function in response to both external or internal moderate resistive loading. The existence of Edi changes in the 3 groups of cats suggests also that diaphragmatic afferents, preserved in both situations, are involved in this response.

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.

Cricothyroid muscle responses to increased chemical drive in awake normal humans

To examine the response of the cricothyroid muscle (CT) to increased chemical drive, we measured its electromyogram simultaneously with that of the alae nasi (AN) in seven normal awake subjects. During both progressive hyperoxic hypercapnia and hypoxia, peak integrated inspiratory activity (moving time average, MTA) of the CT and AN increased as a power function of mean inspiratory flow (ratio of tidal volume to inspiratory time, VT/TI), given by MTA = a(VT/TI)b + c (where a, b, and c are constants). The exponent b varied from 0.009 to 3.4 among subjects but was correlated between CT and AN both during hypercapnia (r = 0.86) and hypoxia (r = 0.81). The onset of inspiratory activity of the CT and AN preceded that of inspiratory flow. Expressed as a percentage of expiratory time, the CT lead time rose from 7% at rest to 20% during hyperpnea. The corresponding values for the AN were from 22 to 52% (both P less than 0.03). Thus the pattern of response of the CT and AN is similar and related to that of the inspiratory muscles in a curvilinear manner. The findings suggest that during chemical stimulation the electrical activity of the CT is analogous to that of the AN, an upper airway dilator.

Effect of withdrawal of respiratory CO2 oscillations on respiratory control at rest

We examined the effect of sudden withdrawal of respiratory oscillations of arterial PCO2 (CO2 oscillations) at resting metabolic rate on the control of respiration in 11 anesthetized paralyzed vagotomized dogs in normoxic normocapnia. A double-lumen endotracheal tube was inserted so that the left and right lungs were ventilated independently. By alternately ventilating each lung, we could completely abolish CO2 oscillations without affecting the mean blood gas levels (withdrawal of CO2 oscillations). The CO2 oscillation was calculated from arterial pH oscillation measured by a rapidly responding intra-arterial pH electrode. Respiratory center output was monitored by use of a moving time average of the phrenic neurogram. A 3-min period of withdrawal of CO2 oscillations was bracketed by two control periods (simultaneous ventilation of lungs for 3 min) to avoid the confounding effect of the baseline drift in the respiratory center output. The amplitude of the CO2 oscillations in the control was 2.33 +/- 0.89 (SD) Torr. When the difference in the mean level of arterial PCO2 between the control and withdrawal of CO2 oscillations was minimized (-0.09 +/- 0.54 Torr; P greater than 0.25), we found negligible change in the minute phrenic activity during withdrawal of CO2 oscillations (-0.02 +/- 6.11% of the control, P greater than 0.98, n = 49; 99% confidence interval -2.36 to 2.32%). Thus we conclude that the maintenance of normal respiration at rest is not critically dependent on a phasic afferent input to the respiratory center arising from respiratory CO2 oscillations.

Upper airway muscle activity and the thoracic volume dependence of upper airway resistance

Although a thoracic volume dependence of upper airway resistance and caliber is known to exist in seated subjects, the mechanisms mediating this phenomenon are unknown. To test the hypothesis that actively altered end-expiratory lung volume (EELV) affects upper airway resistance in the supine position and to explore the mechanisms of any EELV-induced resistance changes, we studied five normal males during wakefulness. Supraglottic upper airway resistance (Ruaw) was calculated at an inspiratory flow of 0.1 l/s. The genioglossal electromyogram was obtained with indwelling wire electrodes and processed as moving time average. End-tidal CO2 was monitored by infrared analyzer. Observations were made during four 20-breath voluntary maneuvers: two at high and two at low EELV in each subject. Each maneuver was preceded by a control period at functional residual capacity. At high lung volume the EELV was increased by 2.23 +/- 0.54 (SD) liters; Ruaw decreased to 67.8 +/- 35.1% of control, while tonic and phasic genioglossal activities declined to 79.0 +/- 23.1 and 72.4 +/- 29.8%, respectively. At low lung volume the EELV was decreased by 0.86 +/- 0.23 liters. Ruaw increased to 178.2 +/- 186.8%, while tonic and phasic genioglossal activities increased to 243.0 +/- 139.3 and 249.1 +/- 146.3%, respectively (P less than 0.0001 for all). The findings were not explained by CO2 perturbations or respiratory pattern. Multiple linear regression analysis indicated that the genioglossal responses blunted the EELV-induced changes in upper airway patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of varying concentrations of halothane on the activity of the genioglossus, intercostals, and diaphragm in cats: an electromyographic study.

To determine the possible differential effects of depth of inhalation anesthetics on inspiratory muscle activity, the following were studied in seven adult cats: the phasic activity of the diaphragm, the external intercostals, and the genioglossus, by means of electromyography (EMG) and its moving time average (MTA). The animals spontaneously breathed 1.0-3.0% halothane in O2, while arterial PCO2 was maintained constant at approximately 60 mmHg by adjusting CO2 in the inspired gas mixture. Muscle activity was evaluated in terms of peak height of MTA, with measurements at 1% halothane used as control values. Halothane anesthesia attenuated inspiratory muscle activity significantly (P less than 0.05) in a dose-dependent fashion; muscle activity decreased most in the genioglossus, least in the diaphragm, and intermediately in the intercostals. Respiratory frequency, inspiratory time, and inspiratory duty cycle did not change significantly with increasing concentration of halothane.

Expiratory muscle activity in anesthetized children: Effect on the single breath technique

Phasic expiratory activity of the abdominal muscles occurs in adults during halothane anesthesia, but has not been demonstrated in children. If present, abdominal muscle activity would preclude the use of recently developed tests of respiratory mechanics in children during anesthesia. We therefore measured abdominal muscle activity throughout induction of anesthesia with halothane in 10 patients between 1.5 and 9.5 years of age, seven with normal respiratory function and three with chronic airway obstruction. During induction of anesthesia with halothane in N2O and oxygen, the abdominal wall electromyograph (a-EMG) was continuously recorded from surface electrodes. At the same time, the expiratory time constant (tau a) was measured using the single breath test (SBT). The patients were then paralyzed with succinyl choline, and the a-EMG signal and expiratory time constant during paralysis (tau p) were recorded. The raw a-EMG signal and its moving time average were compared with the phase of respiration and with the end-tidal fraction of halothane (Fehalo), and the effect of abdominal muscle activity on tau a was noted. Of the 10 patients, 2 had no abdominal muscle activity at any time during induction. Of the remaining 8 patients, 3 had continuous abdominal muscle activity throughout induction, including one patient with asthma. In the remaining five patients, abdominal muscle activity was present during light halothane anesthesia and disappeared at increased Fehalo. When abdominal muscle activity was present, tau a was significantly less than tau p. It is concluded that abdominal muscle activity in expiration is undetectable during deep halothane anesthesia in most children.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of phasic afferent information on phrenic neural output during hypercapnia.

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.

Ventilatory compensation for changes in functional residual capacity during sleep.

The role of conscious factors in the ventilatory compensation for shortened inspiratory muscle length and the potency of this compensatory response were studied in five normal subjects during non-rapid-eye-movement sleep. To shorten inspiratory muscles, functional residual capacity (FRC) was increased and maintained for 2-3 min at a constant level (range of increase 160-1,880 ml) by creating negative pressure within a tank respirator in which the subjects slept. Minute ventilation was maintained in all subjects over the entire range of increased FRC (mean change +/- SE = -3 +/- 1%) through preservation of tidal volume (-2 +/- 2%) despite slightly decreased breathing frequency (-6 +/- 2%). The decrease in frequency (-13 +/- 2%) was due to a prolongation in expiratory time. Inspiratory time shortened (-10 +/- 1%). Mean inspiratory flow increased 15 +/- 3% coincident with an increase in the slope of the moving time average of the integrated surface diaphragmatic electromyogram (67 +/- 21%). End-tidal CO2 did not rise. In two subjects, control tidal volume was increased 35-50% with CO2 breathing. This augmented tidal volume was still preserved when FRC was increased. We concluded that the compensatory response to inspiratory muscle shortening did not require factors associated with the conscious state. In addition, the potency of this response was demonstrated by preservation of tidal volume despite extreme shortening of the inspiratory muscles and increase in control tidal volumes caused by CO2 breathing. Finally, the timing changes we observed may be due to reflexes following shortening of inspiratory muscle length, increase in abdominal muscle length, or cardiovascular changes.

Effect of inspiratory resistive loading on costal and crural diaphragm electromyograms in piglets.

We examined the effect of inspiratory resistive loaded breathing (IRL) on the electromyographic (EMG) activity of the costal and crural diaphragm in nine anesthetized spontaneously breathing piglets (age 10-23 days, weight 2.8-4.4 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (baseline) and during 30 min of IRL. Thirty min of IRL increased the peak moving time average of both parts of the diaphragm, with the increase in the crural EMG activity (from baseline: 22 +/- 2 to 30 min of IRL: 76 +/- 22 au) exceeding that of costal (from baseline: 23 +/- 2 to 30 min of IRL: 50 +/- 24 au), p less than 0.05. These results 1) suggest that the inspiratory EMG activity of the diaphragm can be differentially distributed between its costal and crural components and 2) document that crural inspiratory EMG activity undergoes greater augmentation under the condition of IRL than does the costal activity in piglets.

Dynamics of respiratory drive and pressure during NREM sleep in patients with occlusive apneas.

To study the dynamics of respiratory drive and pressure in patients with occlusive apneas, diaphragmatic electromyogram (EMGdi), esophageal pressure (Pes), and genioglossal electromyogram (EMGge) were monitored during nocturnal sleep in five patients. Both EMGs were analyzed as peak moving time average, and Pes was quantitated as the peak inspiratory change from base line. During the ventilatory phase both EMGs decreased proportionally. The decrease in Pes was less than the decrease observed in EMGdi, and Pes generated for a given EMGdi increased during the preapneic phase in spite of the proportional decrease in EMGdi and EMGge during this period. We conclude that negative inspiratory pressures which lead to the passive collapse of oropharyngeal walls are dependent on both respiratory and upper airway muscle activity and that occlusive apneas of non-rapid-eye-movement (NREM) sleep do occur in spite of proportional changes observed in the activity of both muscle groups. The preapneic increase in negative inspiratory pressures generated for a given respiratory muscle activity is most likely due to the decrease in upper airway muscle activity that is associated with an increase in oropharyngeal resistance.

Alae nasi electromyographic activity and timing in obstructive sleep apnea.

The alae nasi is an accessible dilator muscle of the upper airway located in the nose. We measured electromyograms (EMG) of the alae nasi to determine the relationship between their activity and timing to contraction of the rib cage muscles and diaphragm during obstructive apnea in nine patients. Alae nasi EMG were measured with surface electrodes and processed to obtain a moving time average. Contraction of the rib cage and diaphragm during apneas was detected with esophageal pressure. During non-rapid-eye-movement (NREM) sleep, there was a significant correlation in each patient between alae nasi EMG activity and the change in esophageal pressure. During rapid-eye-movement (REM) sleep, correlations were significantly lower than during NREM sleep. As the duration of each apnea increased, the activation of alae nasi EMG occurred progressively earlier than the change in esophageal pressure. We conclude that during obstructive apneas in NREM sleep, activity of the alae nasi increases when diaphragm and rib cage muscle force increases and the activation occurs earlier as each apneic episode progresses.

Effects of position on respiratory muscle function during CO2 rebreathing.

The effects of changing from the sitting to supine position on respiratory muscle function was assessed during CO2 rebreathing. Gastric (Pg), pleural (Ppl) and transdiaphragmatic (Pdi) pressures and thoracoabdominal motion were monitored. Diaphragmatic EMG was measured by a bipolar esophageal electrode and quantitated as a moving time average (EMGdi). From sitting to supine, in only 2 of 7 subjects (group A) the diaphragm gained a mechanical advantage as evident by an increased slope of the Pdi versus EMGdi relationship not present in the other 5 subjects (group B). At high levels of ventilation while sitting, only group B increased expiratory abdominal muscle activity leading to a more favorable diaphragm length and a passive descent of the abdomen-diaphragm on inspiration. In the supine position functional residual capacity progressively increased in all subjects and the above abdominal pattern was not seen. We conclude that during upright CO2 rebreathing the recruitment of the expiratory abdominal muscles assists diaphragmatic function by placing the diaphragm in an advantageous pressure generating configuration.

Respiratory responses in reversible diaphragm paralysis.

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.

Effects of electrode position on esophageal diaphragmatic EMG in humans.

The effects of electrode position and gastric-balloon anchoring on esophageal diaphragmatic EMG (EMGdi) responses to CO2 rebreathing were studied in seven normal sitting humans using an esophageal catheter that consisted of four platinum wire coils enabling simultaneous recording of three EMGdi signals from three different sites in the esophagus. A gastric balloon attached to the distal end of the catheter allowed anchoring of the catheter. EMGdi signals were quantitated as a moving time average. Two rebreathing experiments were performed with and without balloon anchoring on the same day. Changes in electrode position of at least 2 cm above the site of maximum EMGdi activity caused minimal changes in the moving average EMGdi and did not significantly effect the quantitated EMGdi response to CO2 rebreathing. The maximum EMGdi activity was approximately 2 cm above the gastroesophageal junction in sitting humans. Stabilization of the catheter with an inflated gastric balloon did not improve the reproducibility of the EMGdi data. Finally, the EMGdi response to two CO2 rebreathing runs done at the same sitting showed intraindividual reproducibility.

Quantification of diaphragmatic EMG response to CO2 rebreathing in humans.

To determine a reliable quantitative method of measuring diaphragmatic EMG (EMGdi), electrical activity of the diaphragm was obtained via an esophageal electrode during CO2 rebreathing in 6 normal males and processed three different ways: 1) integration (area), 2) as a moving time average, and 3) as a moving time variance. Integrated activity was quantified in terms of total activity and inspiratory activity. In addition, average total activity and average inspiratory activity were calculated. Moving average and moving variance were analyzed in terms of rate of rise (slope) and peak activities. All integration parameters, except average inspiratory activity, were poorly correlated to changes in PCO2, minute ventilation, and inspiratory muscle force, during rebreathing. Moving average and variance responses to rebreathing were linear with high correlation coefficients, with the slope measures showing the overall best correlations. There was no significant difference between average and variance EMGdi parameters in their responses to rebreathing. Time-related quantification of EMGdi, including average inspiratory activity, and particularly moving average and moving variance, appear to be reliable methods for quantitating neural drive to the respiratory muscles during CO2 rebreathing.

Phrenic nerve activity and occlusion pressure changes during CO2 rebreathing in cats.

Changes in phrenic nerve activity, quantified as a moving time average, PNG(t), were characterized during complete airway occlusion at functional residual capacity (FRC) and compared to simultaneously occurring changes in intratracheal pressure. In anesthetized cats breathing room air and during CO2 breathing, PNG(t) during occlusion was the same as that found during unobstructed breathing until it reached a value approximately corresponding to that at peak inspiration in the preceding unoccluded breath, the rate of change of PNG(t) usually remained the same but in a few cases (2 out of 11) increased. When intratracheal occlusion pressure was plotted as a function of PNG(t), both while breathing room air and during CO2 rebreathing, an approximately linear relationship was obtained. Thus, changes in intratracheas occlusion pressure obtained at FRC parallel changes in phrenic motor nerve activity. Quantification of electrical activity of respiratory nerves as a moving time average provides a means of characterizing changes in the average level of electrical activity during an inspiratory effort.

Probabilities of moving time averages of a meteorological variate

Probabilities of moving time averages of a meteorological variate

Probabilities of moving time averages of a meteorological variate

A meteorological element, such as the surface air temperature, averaged over a given time interval, can serve as a measure of the persistence or duration of the condition over that time interval. To study the probability distribution of moving time averages involving both common and extreme averages, it was found necessary to use a Monte Carlo simulation technique. A simple Markov process generating a sequence of values of a normally distributed variate, characterized by a constant hour-to-hour correlation, has worked fortuitously well as a model of duration on the selected examples, for the number of hours ranging from one to 768. Charts have been prepared to give the probability distribution of the highest m -hour average in n hours, where n is equal to the number of hours in one day, 8 days or 32 days, and m is equal to 1, 3, 6, 12, 24, 48, 96, 192, 384 or 768 hours. The hour-to-hour correlation, in this study, ranges from zero to 0.999, with the usual value approximately 0.95. DOI: 10.1111/j.2153-3490.1968.tb00387.x