Dissociation between diaphragmatic and rib cage muscle fatigue

To assess rib cage muscle fatigue and its relationship to diaphragmatic fatigue, we recorded the electromyogram (EMG) of the parasternal intercostals (PS), sternocleidomastoid (SM), and platysma with fine wire electrodes and the EMG of the diaphragm (DI) with an esophageal electrode. Six normal subjects were studied during inspiratory resistive breathing. Two different breathing patterns were imposed: mainly diaphragmatic or mainly rib cage breathing. The development of fatigue was assessed by analysis of the high-to-low (H/L) ratio of the EMG. To determine the appropriate frequency bands for the PS and SM, we established their EMG power spectrum by Fourier analysis. The mean and SD for the centroid frequency was 312 +/- 16 Hz for PS and 244 +/- 48 Hz for SM. When breathing with the diaphragmatic patterns, all subjects showed a fall in H/L of the DI and none had a fall in H/L of the PS or SM. During rib cage emphasis, four out of five subjects showed a fall in H/L of the PS and five out of six showed a fall in H/L of the SM. Four subjects showed no fall in H/L of the DI; the other two subjects were unable to inhibit diaphragm activity to a substantial degree and did show a fall in H/L of the DI. Activity of the platysma was minimal or absent during diaphragmatic emphasis but was usually strong during rib cage breathing. We conclude that fatigue of either the diaphragm or the parasternal and sternocleidomastoid can occur independently according to the recruitment pattern of inspiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of respiratory muscle unloading on exercise-induced diaphragm fatigue.

We previously compared the effects of increased respiratory muscle work during whole body exercise and at rest on diaphragmatic fatigue and showed that the amount of diaphragmatic force output required to cause fatigue was reduced significantly during exercise (Babcock et al., J Appl Physiol 78: 1710, 1995). In this study, we use positive-pressure proportional assist ventilation (PAV) to unload the respiratory muscles during exercise to determine the effects of respiratory muscle work, per se, on exercise-induced diaphragmatic fatigue. After 8-13 min of exercise to exhaustion under control conditions at 80-85% maximal oxygen consumption, bilateral phrenic nerve stimulation using single-twitch stimuli (1 Hz) and paired stimuli (10-100 Hz) showed that diaphragmatic pressure was reduced by 20-30% for up to 60 min after exercise. Usage of PAV during heavy exercise reduced the work of breathing by 40-50% and oxygen consumption by 10-15% below control. PAV prevented exercise-induced diaphragmatic fatigue as determined by bilateral phrenic nerve stimulation at all frequencies and times postexercise. Our study has confirmed that high- and low-frequency diaphragmatic fatigue result from heavy-intensity whole body exercise to exhaustion; furthermore, the data show that the workload endured by the respiratory muscles is a critical determinant of this exercise-induced diaphragmatic fatigue.     

Diaphragmatic work of breathing in premature human infants

Present methods of assessing the work of breathing in human infants do not account for the added load when intercostal muscle activity is lost and rib cage distortion occurs. We have developed a technique for assessing diaphragmatic work in this circumstance utilizing measurements of transdiaphragmatic pressure and abdominal volume displacement. Eleven preterm infants without evidence of lung disease were studied. During periods of minimal rib cage distortion, inspiratory diaphragmatic work averaged 5.9 g X cm X ml-1, increasing to an average of 12.4 g X cm X ml-1 with periods of paradoxical rib cage motion (P less than 0.01). Inspiratory work was strongly correlated with the electrical activity of the diaphragm as measured from its moving time average (P less than 0.05). Assuming a mechanical efficiency of 4% in these infants, the caloric cost of diaphragmatic work may reach 10% of their basal metabolic rate in periods with rib cage distortion. When lung disease is superimposed, the increased metabolic demands of the diaphragm may predispose preterm infants to fatigue and may contribute to a failure to grow.     

Chest wall motion of infants during spinal anesthesia

To test the extent to which diaphragmatic contraction moves the rib cage in awake supine infants during quiet breathing, we studied chest wall motion in seven prematurely born infants before and during spinal anesthesia for inguinal hernia repair. Infants were studied at or around term (postconceptional age 43 +/- 8 wk). Spinal anesthesia produced a sensory block at the T2-T4 level, with concomitant motor block at a slightly lower level. This resulted in the loss of most intercostal muscle activity, whereas diaphragmatic function was preserved. Rib cage and abdominal displacements were measured with respiratory inductance plethysmography before and during spinal anesthesia. During the anesthetic, outward inspiratory rib cage motion decreased in six infants (P less than 0.02, paired t test); four of these developed paradoxical inward movement of the rib cage during inspiration. One infant, the most immature in the group, had inward movement of the rib cage both before and during the anesthetic. Abdominal displacements increased during spinal anesthesia in six of seven infants (P less than 0.05), suggesting an increase in diaphragmatic motion. We conclude that, in the group of infants studied, outward rib cage movement during awake tidal breathing requires active, coordinated intercostal muscle activity that is suppressed by spinal anesthesia.     

Effect of inspiratory muscle fatigue on breathing pattern

Our aim was to determine whether inspiratory muscle fatigue changes breathing pattern and whether any changes seen occur before mechanical fatigue develops. Nine normal subjects breathed through a variable inspiratory resistance with a predetermined mouth pressure (Pm) during inspiration and a fixed ratio of inspiratory time to total breath duration. Breathing pattern after resistive breathing (recovery breathing pattern) was compared with breathing pattern at rest and during CO2 rebreathing (control breathing pattern) for each subject. Relative rapid shallow breathing was seen after mechanical fatigue and also in experiments with electromyogram evidence of diaphragmatic fatigue where Pm was maintained at the predetermined level during the period of resistive breathing. In contrast there was no significant difference between recovery and control breathing patterns when neither mechanical nor electromyogram fatigue was seen. It is suggested that breathing pattern after inspiratory muscle fatigue changes in order to minimize respiratory sensation.     

Effect of inspiratory muscle fatigue on breathing pattern during inspiratory resistive loading

The purpose of this study was to determine whether induction of either inspiratory muscle fatigue (expt 1) or diaphragmatic fatigue (expt 2) would alter the breathing pattern response to large inspiratory resistive loads. In particular, we wondered whether induction of fatigue would result in rapid shallow breathing during inspiratory resistive loading. The breathing pattern during inspiratory resistive loading was measured for 5 min in the absence of fatigue (control) and immediately after induction of either inspiratory muscle fatigue or diaphragmatic fatigue. Data were separately analyzed for the 1st and 5th min of resistive loading to distinguish between immediate and sustained effects. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating a predetermined fraction of either the maximal mouth pressure or maximal transdiaphragmatic pressure until they could no longer reach the target pressure. Compared with control, there were no significant alterations in breathing pattern after induction of fatigue during either the 1st or 5th min of resistive loading, regardless of whether fatigue was induced in the majority of the inspiratory muscles or just in the diaphragm. We conclude that the development of inspiratory muscle fatigue does not alter the breathing pattern response to large inspiratory resistive loads.     

Distortion of chest wall and work of diaphragm in preterm infants

Chest wall distortion is common in infants and is especially visible in preterm infants. It has been suggested that this distortion increases the volume displacement of the diaphragm during inspiration, which may be associated with muscular fatigue and apnea. We studied 10 preterm infants who had no evidence of lung disease, investigating the effect of chest wall distortion on the volume displacement and work of the diaphragm. The volume changes of the respiratory system were partitioned using an inductance plethysmograph. The minute volume displacement and the work of the diaphragm were calculated using the partitioned abdominal volume change and the gastric and esophageal pressures. The paradoxical movement of the chest wall lasted an average of 36% of inspiration. The minute volume displacement of the diaphragm ranged from 72 to 176% of the minute pulmonary ventilation, and diaphragmatic work ranged from 94 to 793% of that performed on the lungs. The amount of chest wall distortion, as reflected by the duration of the paradoxical chest wall movement, the minute volume excursion, or work of the diaphragm, was not related to the mechanical properties of the lungs. This estimated work load may represent a significant expenditure of calories in these infants and may contribute to the development of diaphragmatic fatigue, apnea, and a prolonged need for mechanical ventilation.     

Bilateral phrenic stimulation: a simple technique to assess diaphragmatic fatigue in humans

Transdiaphragmatic pressure (Pdi) and the rate of relaxation of the diaphragm (tau) were measured at functional residual capacity (FRC) in six normal seated subjects during single-twitch stimulation of both phrenic nerves. The latter were stimulated supramaximally with needle electrodes with square-wave impulses of 0.1-ms duration at 1 Hz before and after diaphragmatic fatigue produced by resistive loaded breathing. Constancy of chest wall configuration was achieved by monitoring the diameter of the abdomen and the rib cage with a respiratory inductive plethysmograph system. During control the peak Pdi generated during the phrenic stimulation amounted to 34.4 +/- 4.2 (SE) cmH2O and represented in each subject a fixed fraction (17%) of its maximal transdiaphragmatic pressure. After diaphragmatic fatigue the peak Pdi decreased by an average of 45%, amounting to 18.1 +/- 2.7 cmH2O 5 min after the fatigue run, and tau increased from 55.2 +/- 9 ms during control to 77 +/- 8 ms 5 min after the fatigue run. The decrease in peak Pdi and the increase in tau observed after the fatigue run persisted throughout the 30 min of the recovery period studied, the peak Pdi amounting to 18.4 +/- 2.8 and 18.9 +/- 3.3 cmH2O and tau to 81.3 +/- 5.7 and 88.7 +/- 10 ms at 15 and 30 min after the end of the fatigue run, respectively. It is concluded that diaphragmatic fatigue can be detected in man by bilateral phrenic stimulation with needle electrodes without any discomfort for the subject and that the decrease in diaphragmatic strength after fatigue is long lasting.     

Preferential fatigue of the rib cage muscles during inspiratory resistive loaded ventilation

Because the inspiratory rib cage muscles are recruited during inspiratory resistive loaded breathing, we hypothesized that such loading would preferentially fatigue the rib cage muscles. We measured the pressure developed by the inspiratory rib cage muscles during maximal static inspiratory maneuvers (Pinsp) and the pressure developed by the diaphragm during maximal static open-glottis expulsive maneuvers (Pdimax) in four human subjects, both before and after fatigue induced by an inspiratory resistive loaded breathing task. Tasks consisted of maintaining a target esophageal pressure, breathing frequency, and duty cycle for 3-5 min, after which the subjects maintained the highest esophageal pressure possible for an additional 5 min. After loading, Pinsp decreased in all subjects [control, -128 +/- 14 (SD) cmH2O; with fatigue, -102 +/- 18 cmH2O; P less than 0.001, paired t test]. Pdimax was unchanged (control, -192 +/- 23 cmH2O; fatigue, -195 +/- 27 cmH2O). These data suggest that 1) inability to sustain the target during loading resulted from fatigue of the inspiratory rib cage muscles, not diaphragm, and 2) simultaneous measurement of Pinsp and Pdimax may be useful in partitioning muscle fatigue into rib cage and diaphragmatic components.     

Changes in respiratory muscle activity in conscious cats during experimental dives at 101 ATA.

The rationale for the present study was to test the hypothesis that increased work of breathing during experimental deep diving may lead to respiratory muscle fatigue. For this purpose, electromyograms (EMGs) of respiratory and skeletal muscles, plus electrocardiogram and electroencephalogram (EEG) derivatives, were continuously recorded in conscious cats. In each muscle group, the ratio of power in a high (H) to that in a low (L) band of EMG frequencies was computed. Direct diaphragmatic stimulation in selected animals produced a mass action potential to obtain the muscle fiber conduction velocity (MFCV). The maximal pressure was 101 ATA (1,000 msw) with a maximal duration of 72 h. Four cats breathed an He-O2 mixture and five others a ternary mixture (10% N2 in He-O2). Inspired O2 partial pressure was 350 Torr. With the He-O2 mixture, all the animals died within 2-54 h during the study at maximal depth. EEG signs of high-pressure nervous syndrome (HPNS) were present in all cats, and low-frequency (11-14 Hz) hyperbaric tremor discontinuously contaminated all EMG tracings. The H/L ratio computed from diaphragmatic and intercostal muscle EMGs increased after 12 h at 101 ATA. With the He-N2-O2 mixture, the cats survived until the end of the sojourn at 101 ATA, during which no hyperbaric tremor was detected from EMG tracings, and EEG signs of HPNS were weak or absent. From 31 ATA, the H/L ratio decreased significantly in respiratory but not in skeletal muscles; this was associated with decreased MFCV in the diaphragm after several hours at maximal depth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of theophylline on the velocity of diaphragmatic muscle shortening

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory modulation of human autonomic rhythms

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.     

Effects and mechanism of action of terbutaline on diaphragmatic contractility and fatigue

We studied the effects of intravenously administered terbutaline on diaphragmatic force and fatigue during electrical stimulation of the diaphragm in 17 anesthetized dogs. The diaphragm was stimulated indirectly through the phrenic nerves with electrodes placed around the fifth roots and directly with electrodes surgically implanted in the abdominal side of each hemidiaphragm. Transdiaphragmatic pressure (Pdi) during direct or indirect supramaximal 2-s stimulation applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. In seven dogs the administration of terbutaline (0.5 mg) had no effect on Pdi at any stimulation frequency applied directly or indirectly. The effect of terbutaline (0.5 mg) on diaphragmatic fatigue was then tested in 10 other dogs. Diaphragmatic fatigue was produced by continuous 20-Hz electrical supramaxial stimulation of the phrenic nerves during 30 min. At the end of the fatigue procedure Pdi decreased by 50 +/- 5 and 30 +/- 8% of control values at 10 and 100 Hz, respectively, for either direct or indirect stimulation. The decrease in Pdi for low frequencies of stimulation (10 and 20 Hz) lasted 100 +/- 18 min, whereas it lasted only 40 +/- 10 min for the high frequencies (50 and 100 Hz). When terbutaline (0.5 mg) was administered after the fatiguing procedure, Pdi increased within 15 min by 20 +/- 4% at 10 Hz and by 12 +/- 3% at 100 Hz for either direct or indirect stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of inspiratory resistive loaded breathing and hypoxemia on diaphragmatic function in the piglet.

The combined effects of inspiratory resistive loaded breathing (IRL) and hypoxemia on transdiaphragmatic pressure (Pdi) in nine 1-mo-old Yorkshire piglets were studied. IRL was adjusted to increase spontaneously generated Pdi five to six times above baseline but maintain arterial PCO2 < 70 Torr to prevent hypercapnic depression of diaphragmatic contractility. Measurements of ventilation, blood gases and pH, Pdi, diaphragmatic electromyogram, Pdi during phrenic nerve stimulation, diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 2 h of IRL, and then after 1 h of hypoxemia (arterial PO2 approximately 40 Torr) combined with IRL. Diaphragmatic muscle samples were obtained after study completion and immediately frozen in liquid nitrogen for determination of tissue ATP, phosphocreatine, lactate, and glycogen levels. Ten 1-mo-old piglets were subjected to IRL alone and served as controls. IRL alone resulted in significant impairment of Pdi generation. The addition of hypoxemia for 1 h did not further compromise Pdi in comparison to control animals who were subjected to IRL alone. Blood flow to both the costal and crural segments of the diaphragm increased significantly during IRL; the addition of the hypoxemic stress resulted in further significant augmentation of blood flow to both segments of the diaphragm. No differences were noted in diaphragmatic muscle tissue ATP, phosphocreatine, or glycogen between control and IRL animals or between control and IRL plus hypoxemia animals. Muscle lactate levels increased significantly in the IRL plus hypoxemia animals only. The data from this study suggest that moderate hypoxemia during resistive-loaded breathing in the piglet does not accentuate diaphragmatic fatigue.     

Diaphragm fatigue induced by inspiratory resistive loading in spontaneously breathing rabbits

Diaphragmatic contractility was assessed in spontaneously breathing ketamine-anesthetized rabbits by measuring the strength of diaphragmatic contraction in response to bilateral supramaximal phrenic nerve stimulation at frequencies between 10 and 100 Hz. During 10-180 min of inspiratory resistive loading, contractility decreased by approximately 40%, and hypoxemia and both respiratory and lactic acidosis developed. After 10 min of recovery, both the response to high-frequency stimulation (100 Hz) and the arterial PO2 and PCO2 returned to base-line levels, whereas metabolic acidosis and reduced response to low-frequency stimulation (10-20 Hz) persisted. Similar levels of hypoxemia and respiratory acidosis in the absence of inspiratory resistive loading did not alter diaphragmatic contractility. We conclude that in anesthetized rabbits excessive inspiratory resistive loading results in partially reversible diaphragm fatigue of the high- and low-frequency types, accompanied by hypoventilation and lactic acidosis.     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Airway obstruction during periodic breathing in premature infants

To characterize changes in pulmonary resistance, timing, and respiratory drive during periodic breathing, we studied 10 healthy preterm infants (body wt 1,340 +/- 240 g, postconceptional age 35 +/- 2 wk). Periodic breathing in these infants was defined by characteristic cycles of ventilation with intervening respiratory pauses greater than or equal to 2 s. Nasal airflow was recorded with a pneumotachometer, and esophageal or pharyngeal pressure was recorded with a fluid-filled catheter. Pulmonary resistance at half-maximal tidal volume, inspiratory time (TI), expiratory time (TE), and mean inspiratory flow (VT/TI) were derived from computer analysis of five cycles of periodic breathing per infant. In 80% of infants periodic breathing was accompanied by completely obstructed breaths at the onset of ventilatory cycles; the site of airway obstruction occurred within the pharynx. The first one-third of the ventilatory phase of each cycle was accompanied by the highest airway resistance of the entire cycle (168 +/- 98 cmH2O.l-1.s). In all infants TI was greatest at the onset of the ventilatory cycle, VT/TI was maximal at the midpoint of the cycle, and TE was longest in the latter two-thirds of each cycle. A characteristic increase and subsequent decrease of 4.5 +/- 1.9 ml in end-expiratory volume also occurred within each cycle. These results demonstrate that partial or complete airway obstruction occurs during periodic breathing. Both apnea and periodic breathing share the element of upper airway instability common to premature infants.     

Respiratory muscle interaction during NREM sleep in patients with occlusive apnea

To study respiratory muscle interaction in patients with occlusive apnea, diaphragmatic electromyogram (EMGdi) and gastric, pleural, and transdiaphragmatic pressures (Pga, Ppl, and Pdi, respectively) were studied in seven patients during non-rapid-eye-movement (NREM) sleep. Diaphragmatic force output, as assessed by Pdi, followed the periodic changes in EMGdi but during the occlusive phase the increase in Pdi was more than the increase in EMGdi. This increase in Pdi was essentially due to an increase in Ppl, since Pga and EMGdi had a linear relationship (r = 0.98, P less than 0.001) that did not change during the occlusive and ventilatory phases. Abdominal muscle recruitment evident in Pga and abdominal motion tracings during the occlusive phase when paradoxical rib cage motion was observed suggested that this increase in diaphragmatic efficiency was likely due to a change in diaphragmatic length-tension characteristics. These results demonstrate that, in patients with occlusive apneas, the diaphragm is the predominant respiratory muscle during NREM sleep and that its function is supported by abdominal muscle recruitment.     

Changes in afferent and efferent phrenic activities with electrically induced diaphragmatic fatigue.

In anesthetized artificially ventilated cats, diaphragmatic fatigue was produced by direct muscle stimulation with trains of pulses for 30 min. Failure of contraction was assessed from decrease in the maximal relaxation rate of transdiaphragmatic pressure twitches. Motor activities (electromyogram and motor phrenic neurogram) were processed by fast-Fourier transform analysis, which provided the power spectrum density function (PSDF). The discharge frequency of diaphragmatic afferents was also measured. In control conditions (before fatigue), intra-arterial bolus injection of lactic acid enhanced tonically active diaphragmatic afferents, whereas it reduced the firing rate of afferent fibers activated in phase with diaphragmatic contraction or relaxation. The same sensory response pattern was observed with the development of diaphragmatic fatigue. Leftward shift in PSDFs of motor phrenic neurogram also occurred, but it preceded the failure of diaphragmatic contraction as well as the changes in the electromyogram's PSDF and afferent paths, which were closely associated with lengthening of both inspiratory and total breath durations. After section of the phrenic nerves, the motor phrenic response disappeared during the fatigue trial. This demonstrates the existence of complex reflex-induced changes in the ventilatory control during diaphragmatic fatigue. They seem to involve the participation of several types of phrenic afferents.     

Periodicities in respiration and heart rate in newborns

Periodic breathing is common in normal infants, but may be associated with prolonged apnea leading to crib death. The mechanisms of periodic breathing and its relation to normal breathing patterns are unclear. We recorded respiratory and heart rate (HR) patterns of 11 healthy newborn infants during quiet sleep, in both normal and periodic breathing. Spectral analysis of the respiratory pattern revealed a low-frequency (LF) periodicity in normal breathing approximately equal to the frequency of periodic breathing when this occurs. Periodic breathing thus appears to be an exaggeration of an underlying slow amplitude variation which is present in regular breathing. LF periodicity also appeared in the HR pattern in both normal and periodic breathing, suggesting an LF modulation of cardiovascular control as well. The lack of a definite phase relation between HR and ventilation at LF may indicate dominant peripheral, rather than central, interactions between HR and respiration at these frequencies.