Respiratory Muscle Responses Research Articles

Respiratory muscle coordination and diaphragm length during expiratory threshold loading

Active expiration is produced by the abdominal muscles and the rib cage expiratory muscles. We hypothesized that the relative contribution of these two groups to expiration would affect diaphragmatic length and, hence, influence the subsequent inspiration. To address this question we measured the respiratory muscle response to expiratory threshold loading in spontaneously breathing anesthetized dogs. Prevagotomy, the increase in lung volume (functional residual capacity) and decrease in initial resting length of the diaphragm were attenuated by greater than 50% of values predicted by the passive relationships. Diaphragmatic activation (electromyogram) increased and tidal volume (VT) was preserved. Postvagotomy, effective expiratory muscle recruitment was abolished. The triangularis sterni muscle remained active, and the increase in lung volume was attenuated by less than 15% of that predicted by the passive relationship. Diaphragmatic length was shorter than predicted. VT was not restored, even though costal diaphragmatic and parasternal intercostal electromyogram increased. During expiratory threshold loading with abdominal muscles resected and vagus intact, recruitment of the rib cage expiratory muscles produced a reduction in lung volume comparable with prevagotomy; however, diaphragmatic length decreased markedly. Both the rib cage and abdominal expiratory muscles may defend lung volume; however, their combined action is important to restore diaphragmatic initial length and, accordingly, to preserve VT.

An isometric method to study respiratory smooth muscle responses in mice

An isometric method to measure the smooth muscle tone of murine tracheas in vitro was developed. Nine trachea rings from just beneath the larynx were prepared free of excess tissue with the help of a binocular microscope. These trachea parts were slipped onto supports in an organ bath containing Krebs' solution. Isometric tension was measured with a force displacement transducer connected to the upper-trachea support, and is expressed as changes in grams force. The cholinergic agonist carbachol contracted isolated tracheas. Serotonin also induced contractions, but was less potent than carbachol. Histamine induced tracheal contractions only at very high concentrations. Sympathomimetic β adrenergic agonists relaxed carbachol-precontracted tracheas with the following order of potency: isoprenaline (β 1 and β 2 adrenoceptor agonist) > salbutamol (β 2 adrenoceptor agonist) > prenalterol (β 1 adrenoceptor agonist). Adrenaline and noradrenaline relaxed carbachol-precontracted tracheas, with adrenaline being the more potent relaxant. For the study of airway reactivity, this mouse trachea model has several advantages over immunopharmacologic models: The immune system of the mouse has been characterized extensively, and many reagents are available to study the immune system and, thus, possible interactions of this system with pharmacological mechanisms. Other animal models used in pharmacology are generally less well defined immunologically.

Inspiratory and expiratory muscle function during continuous positive airway pressure in dogs

Continuous positive airway pressure (CPAP) is known to produce activation of the expiratory muscles. Several factors may determine whether this activation can assist inspiration. In this study we asked how and to what extent expiratory muscle contraction can assist inspiration during CPAP. Respiratory muscle response to CPAP was studied in eight supine anesthetized dogs. Lung volume and diaphragmatic initial length were defended by recruitment of the expiratory muscles. At the maximum CPAP of 18 cmH2O, diaphragmatic initial lengths were longer than predicted by the passive relationship by 52 and 46% in the costal and crural diaphragmatic segments, respectively. During tidal breathing after cessation of expiratory muscle activity, a component of passive inspiration occurred before the onset of inspiratory diaphragmatic electromyogram (EMG). At CPAP of 18 cmH2O, passive inspiration represented 24% of the tidal volume (VT) and tidal breathing was within the relaxation characteristic. Diaphragmatic EMG decreased at CPAP of 18 cmH2O; however, VT and tidal shortening were unchanged. We identified passive and active components of inspiration. Passive inspiration was limited by the time between the cessation of expiratory activity and the onset of inspiratory activity. We conclude that increased expiratory activity during CPAP defends diaphragmatic initial length, assists inspiration, and preserves VT. Even though breathing appeared to be an expiratory act, there remained a significant component of active inspiratory diaphragmatic shortening, and the major portion of VT was produced during active inspiration.

Respiratory muscle responses to changes in chemoreceptor drive in infants

Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea.

Genioglossus and diaphragm activity during obstructive apnea and airway occlusion in infants.

To document mechanisms contributing to upper airway collapse, we compared the electromyographic activity of the genioglossus (GG) and diaphragm (DIA) during spontaneous mixed and obstructive apnea and during induced end-expiratory airway occlusion in 11 premature infants. In addition to ventilation and esophageal pressure measurements, we obtained DIA and GG electromyograms (EMG) from subcostal and sublingual surface electrodes, respectively. Amplitude of the DIA EMG and the frequency of occurrence of the GG EMG were determined for: 1) the breath preceding apnea or occlusion, 2) the initial and last obstructed inspiratory efforts, and 3) the first breath at resolution of both apnea and occlusion. During spontaneous apnea with airway obstruction amplitude of the DIA, EMG decreased on the initial obstructed inspiratory effort and did not exceed that of the breath preceding apnea until reestablishment of flow. In contrast, during end-expiratory airway occlusion, the amplitude of the DIA EMG increased both during and at release of occlusion. In 18 +/- 6% of the spontaneous apneic episodes, GG EMG was present with the breath preceding apnea and this frequency did not increase significantly until resolution of the apnea. During induced airway occlusion, GG EMG was not present with the breath preceding occlusion but its frequency did increase to 58 +/- 8 and 42 +/- 8% with the last occluded inspiratory effort and the first breath after release of occlusion, respectively. The decreased presence of the GG EMG from the last occluded effort to the breath at release of occlusion (58 +/- 8 versus 42 +/- 8%, p less than 0.05) was probably due to the greater mechanoreceptor-mediated inhibition associated with reestablishment of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of platelet-activating factor on leukotriene D4-induced contractions of the guinea pig parenchymal strip.

Platelet-activating factor (PAF) and sulphidopeptide leukotrienes, such as leukotriene D4 (LTD4), are potent constrictors that are probably released simultaneously in a variety of inflammatory respiratory events. The purpose of the present study was to determine whether LTD4-induced contractions of guinea pig parenchymal lung strips (GPPS) are modified in the presence of PAF. The contractile responses of isolated GPPS to cumulative doses of LTD4, acetylcholine, histamine, and potassium chloride in the presence of PAF (0.1 nM, 0.1 microM) were compared with parallel controls. There was no significant alteration of the response to acetylcholine and potassium chloride and the PAF-induced inhibition of the response to histamine, although significant, was not concentration dependent. In contrast, PAF in a concentration range from 0.1 nM to 1.0 microM caused a marked, concentration-dependent reduction of LTD4-induced contractions. Pretreatment with the PAF receptor antagonist, BN52021, prevented the attenuation of LTD4-induced contraction by PAF. The attenuation of LTD4-induced contraction by PAF was also prevented by pretreatment with indomethacin or with the thromboxane synthase inhibitor U63,557A, but not by pretreatment with the lipoxygenase inhibitors BW755c or nordihydroguaiaretic acid. Thus inhibition of LTD4-induced GPPS contraction by PAF is receptor dependent and probably secondary to thromboxane generation. The respiratory smooth muscle response to leukotrienes may be modified significantly by concomitant PAF release.

Upper airway and respiratory muscle responses to continuous negative airway pressure

To determine upper airway and respiratory muscle responses to nasal continuous negative airway pressure (CNAP), we quantitated the changes in diaphragmatic and genioglossal electromyographic activity, inspiratory duration, tidal volume, minute ventilation, and end-expiratory lung volume (EEL) during CNAP in six normal subjects during wakefulness and five during sleep. During wakefulness, CNAP resulted in immediate increases in electromyographic diaphragmatic and genioglossal muscle activity, and inspiratory duration, preserved or increased tidal volume and minute ventilation, and decreased EEL. During non-rapid-eye-movement and rapid-eye-movement sleep, CNAP was associated with no immediate muscle or timing responses, incomplete or complete upper airway occlusion, and decreased EEL. Progressive diaphragmatic and genioglossal responses were observed during non-rapid-eye-movement sleep in association with arterial O2 desaturation, but airway patency was not reestablished until further increases occurred with arousal. These results indicate that normal subjects, while awake, can fully compensate for CNAP by increasing respiratory and upper airway muscle activities but are unable to do so during sleep in the absence of arousal. This sleep-induced failure of load compensation predisposes the airways to collapse under conditions which threaten airway patency during sleep. The abrupt electromyogram responses seen during wakefulness and arousal are indicative of the importance of state effects, whereas the gradual increases seen during sleep probably reflect responses to changing blood gas composition.

Differential responses of expiratory muscles to chemical stimuli in awake dogs

We assessed respiratory muscle response patterns to chemoreceptor stimuli (hypercapnia, hypoxia, normocapnic hypoxia, almitrine, and almitrine + CO2) in six awake dogs. Mean electromyogram (EMG) activities were measured in the crural (CR) diaphragm, triangularis sterni (TS), and transversus abdominis (TA). Hypercapnia and normocapnic hypoxia caused mild to marked hyperpnea [2-5 times control inspiratory flow (VI)] and increased activity in CR diaphragm, TS, and TA. When hypocapnia was permitted to develop during hypoxia and almitrine-induced moderate hyperpnea, CR diaphragm activity increased, whereas TS and TA activities usually did not change or were reduced below control. Over time in hypercapnia, CR diaphragm, TS, and TA were augmented and maintained at these levels over many minutes; with hypoxic hyperventilation CR diaphragm, TS, and TA were first augmented but then CR diaphragm remained augmented while TS and, less consistently, TA were inhibited over time. Marked hyperpnea (4-5 times control) due to carotid body stimulation increased TA and TS EMG activity despite an accompanying hypocapnia. We conclude that in the intact awake dog 1) carotid body stimulation augments the activity of both inspiratory and expiratory muscles; 2) hypocapnia overrides the augmenting effect of carotid body stimulation on expiratory muscles during moderate hyperpnea, usually resulting in either no change or inhibition; 3) at higher levels of hyperpnea both chemoreceptor stimulation and stimulatory effects secondary to a high ventilatory output favor expiratory muscle activation; these effects override any inhibitory effects of a coincident hypocapnia; and 4) expiratory muscles of the rib cage/abdomen may be augmented/inhibited independently of one another.

Naloxone enhances the response to hypercampia of spinal and cranial respiratory nerves

To assess the effects of endogenous opiates on respiratory muscle responses to CO 2, naloxone was administered intravenously to paralyzed, vagotomized and artificially ventilated cats anesthetized with alpha-chloralose. Neural activity was recorded from the phrenic, hypoglossal *HG), glossopharyngeal (GP) and recurrent laryngeal (RL) nerves. Before naloxone, phasic activity began first in the phrenic at a P et CO2 of 30.0±1.8 Torr, followed by the RL at a P et CO2 of 33.5±1.7 Torr, the HG at a P et CO2 of 39.9±2.1 Torr and the GP at a P et CO2 of 42.5±2.2 Torr during CO 2 rebreathing. Naloxone had no significant effect on the apneic threshold of any of the nerves studied. Naloxone did, however, increase respiratory frequency ( P<0.01) mainly by causing a significant ( P<0.01) shortening of TE as it had no significant effect on TI. Naloxone also significantly the rate at which peak nerve activity increased with CO 2 in the HG ( P<0.01) at the GP ( P<0.01) nerves, but not in the phrenic and RL nerves. Instead, the maximum activity produced by hypercapnia and the P et CO2 level at which maximum activity occurred in the phrenic, but not the RL, increased after naloxone. The result of these effects was that naloxone extended the range over which the HG and GP behaved proportionally with the phrenic, but it did not change the curvilinear nature of these relationships.

Respiratory muscle response to load and glycogen content in type I and II fibers

To study the relation between the response of respiratory muscle to inspiratory loads and glycogen content, we subjected unanesthetized sheep to moderate and severe inspiratory flow resistive (IFR) loads. Only severe IFR loads eventually led to a decrease in transdiaphragmatic pressure ( P di) and a concomitant rise in P aCO 2. Respiratory and nonrespiratory skeletal muscle samples were obtained at necropsy. Glycogen content was determined biochemically in muscle homogenates. Frozen sections were stained with periodic acid-Schiff (PAS) for glycogen and fibers were typed using myosin ATPase stain. Fibers were categorized as full, intermediate, or devoid of glycogen by a subjective scoring system of PAS staining intensity. We found that glycogen content decreased in the costal and crural diaphragm and in the intercostal muscles as the duration of moderate IFR loaded breathing was increased. With severe loads glycogen content decreased significantly, reaching about 40 and 22% of control levels in the costal and crural diaphragm, respectively ( P < 0.01). In addition, with severe IFR loads, a statistically significant proportion of both type I and type II muscle fibers was depleted of glycogen when compared with that of controls ( P < 0.05), but more type II fibers were depleted than type I fibers (50 vs 23%). These data indicate that in sheep subjected to IFR loads: (1) glycogen content in the respiratory muscles decreases as the severity and duration of loaded breathing increases and (2) respiratory muscle fatigue occurs at a time when considerable glycogen is still present in type I fibers in the diaphragm.

Inspiratory muscle responses to airway occlusion during learned breathing movements.

Respiratory muscle responses to sudden obstruction of learned breathing movements were studied in seven normal adults. Subjects were trained to inspire at a constant rate (0.4 liters/s), or maintain a static inspiratory effort(-10 cmH2O). On each trial these efforts were loaded unpredictably by occluding the airway or applying an opposing negative pressure at the mouth. Surface EMGs were recorded from the neck, parasternal intercostal, pectoral, diaphragmatic, and abdominal muscles. The latency and pattern of the responses to occlusion or to negative pressure were obtained from 10-trial computer-averaged records. When subjects were trained to relax in response to loading, inhibitory responses (mean latency: 32 ms) were recorded from the neck (16 out of 21 10-trial averages), diaphragm (9 out of 21), and parasternal (3 out of 21) locations. Excitatory responses (mean latency: 69 ms) were also recorded from the neck (11 out of 21 10-trial averages), diaphragm (8 out of 21), and parasternal (1 out of 21) sites. These responses were also observed in many single trial records. When subjects were trained to make an additional inspiratory effort as quickly as possible after loading, the reaction was a high-amplitude EMG burst, sometimes preceded by a brief inhibitory response. The mean reaction times for the large bursts were: 70 ms for the neck, 86 ms for the diaphragm, and 91 ms for the parasternal intercostals. Latencies in the 60- to 70-ms range were found on many 10-trial averages. Because the latencies of the excitatory responses evoked when subjects were trained to relax in response to loading were similar to those of the EMG bursts recorded when subjects were trained to react quickly in response to loading, it is not possible to distinguish long-latency reflex and learned response components on the basis of latency alone. Previous work, which has assumed that responses in the 50- to 70-ms latency range must be reflexive rather than learned, may need to be reexamined.

Differential response of respiratory muscles to airway occlusion in infants.

The effect of end-expiratory occlusion on respiratory muscle activity was studied in 10 unsedated preterm infants during sleep. Electromyograms (EMG) of the upper airway were recorded from surface electrodes placed over the submental (SM) area; diaphragm (DIA) EMGs were obtained with identical electrodes over the right subcostal margin. Phasic SM EMG accompanied 56 +/- 36% of breaths during spontaneous breathing and increased to 80 +/- 26% (P less than 0.05) on the first inspiratory effort after occlusion. Occlusion increased peak amplitude (P less than 0.001) and total duration (P less than 0.005) of the SM EMG without significant changes in its initial rate of rise. In contrast, only the total duration of the DIA EMG increased (P less than 0.005) during occlusion. Inspiratory time increased from 470 +/- 120 to 720 +/- 210 ms (P less than 0.001) during the first occluded effort, but expiratory time did not change. With sustained occlusion, peak amplitude of the SM EMG progressively increased, but DIA EMG only significantly increased by the third occluded effort. Pharyngeal patency was invariably maintained throughout the induced airway occlusions. Sharp bursts of SM EMG activity coincided with resolution of spontaneous obstructive apneic episodes in four infants. The immediate increase in SM EMG associated with airway occlusion may be a mechanism that prevents the development of obstructive apnea.

On the measurement of vascular and respiratory smooth muscle responses in vitro.

The action of drugs on circular smooth muscle from rabbit renal artery, renal vein, mesenteric vein, inferior vena cava, guinea pig bronchus, and mouse trachea was studied using an inexpensive modification of the method of Bevan, Nielsen and Owman, and Bevan and Osher. Two 30-gauge disposable stainless steel hypodermic needles supported the tissue rings in a standard 10-ml isolated muscle bath. All the blood vessels contracted to norepinephrine, histamine, and KCl. The veins, unlike the renal artery, did not respond maximally to KCl and did not contract at all to serotonin. The guinea pig bronchi contracted to carbachol, histamine, and KCl and relaxed to isoproterenol. The mouse trachea contracted maximally to carbachol, did not contract to histamine, and contracted to 50% of maximum in response to KCl. Thus, standard isolated tissue baths can be inexpensively adapted for the study of relatively small blood vessels and airways (about 1 mm in diameter).

Electromyographic response of respiratory muscles during elastic loading.

The response of respiratory motor neurons to graded elastic loading was assessed in anesthetized dogs by recording the electromyogram (EMG) from the diaphragm (ED) and the intercostal muscle (EIC). Elastic loads were applied for 1-20 breaths. The effects of changes in PCO2 on respiratory motor neuron output was assessed by applying loads during the course of CO2 rebreathing. On the first loaded breath, ED and EIC increased reflexly due chiefly to prolongation of inspiration. Vagotomy or vagal cooling to block the Hering-Breuer reflex eliminated the increase in ED and diminished the increase in EIC. During the second to fifth breath, the level of EMG activity was disproportionately high for the level of PCO2, suggesting an additional reflex component over and above the reflex activity present on the first loaded breath.

Measurement of diaphragmatic blood flow in dogs from xenon 133 clearance.

ArticleMeasurement of diaphragmatic blood flow in dogs from xenon 133 clearance.D F Rochester, and M Pradel-GuenaD F Rochester, and M Pradel-GuenaPublished Online:01 Jan 1973https://doi.org/10.1152/jappl.1973.34.1.68MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByMechanical ventilation weaning issues can be counted on the fingers of just one hand: part 113 March 2020 | The Ultrasound Journal, Vol. 12, No. 1Differences in Respiratory Muscle Responses to Hyperpnea or Loaded Breathing in COPD25 December 2019 | Medicine & Science in Sports & Exercise, Vol. 52, No. 5Human respiratory muscle blood flow measured by near-infrared spectroscopy and indocyanine greenJordan A. Guenette, Ioannis Vogiatzis, Spyros Zakynthinos, Dimitrios Athanasopoulos, Maria Koskolou, Spyretta Golemati, Maroula Vasilopoulou, Harrieth E. Wagner, Charis Roussos, Peter D. Wagner, and Robert Boushel1 April 2008 | Journal of Applied Physiology, Vol. 104, No. 4The Impact of Morbid Obesity on Oxygen Cost of Breathing (V˙ o2RESP ) at RestAmerican Journal of Respiratory and Critical Care Medicine, Vol. 160, No. 3Distribution of diaphragm blood flow during sevoflurane anaesthesia in dogsCanadian Journal of Anaesthesia, Vol. 43, No. 1Pharmacotherapy of the Respiratory MuscleDiaphragmatic fatigue and its recovery are influenced by cardiac outputJournal of Anesthesia, Vol. 5, No. 1Pharmacologic Strategies for Treating Respiratory FailureChest, Vol. 97, No. 3Efficiency of Work of Inspiratory Muscles in Standing and in Exercising DogsChest, Vol. 94, No. 5Respiratory Muscle Energetics1 January 2011Inspiratory Muscle Fatigue1 January 2011Breathing During Exercise1 January 2011Adaptation of Respiratory Muscles to Acute and Chronic StressClinics in Chest Medicine, Vol. 7, No. 1Respiratory muscles: A review of old and newer conceptsLung, Vol. 157, No. 1Diaphragmatic blood flow at various levels of ventilation in the rabbitActa Physiologica Scandinavica, Vol. 106, No. 1Perfusion of inspiratory muscles at different levels of ventilation in rabbitsRespiration Physiology, Vol. 20, No. 2 More from this issue > Volume 34Issue 1January 1973Pages 68-74 https://doi.org/10.1152/jappl.1973.34.1.68PubMed4572509History Published online 1 January 1973 Published in print 1 January 1973 Metrics

Scalene and sternomastoid muscle function.

Scalene and sternomastoid muscle function.