Inspiratory Intercostal Muscles Research Articles

Wavelet Analysis of Respiratory Muscle sEMG Signals during the Physiological Breakpoint of Static Dry End-Expiratory Breath-Holding in Naive Apneists: A Pilot Study.

The wavelet spectral characteristics of three respiratory muscle signals (scalenus (SC), parasternal intercostal (IC), and rectus abdominis (RA)) and one locomotor muscle (brachioradialis (BR)) were analyzed in the time-frequency (T-F) domain during voluntary breath-holding (BH), with a focus on the physiological breakpoint that is commonly considered the first involuntary breathing movement (IBM) that signals the end of the easy-going phase of BH. The study was performed for an end-expiratory BH physiological breaking point maneuver on twelve healthy, physically active, naive breath-holders/apneists (six professional athletes; six recreational athletes, and two individuals in the post-COVID-19 period) using surface electromyography (sEMG). We observed individual effects that were dependent on muscle oxygenation and each person's fitness, which were consistent with the mechanism of motor unit (MU) recruitment and the transition of slow-twitch oxidative (type 1) to fast-twitch glycolytic (type 2) muscle fibers. Professional athletes had longer BH durations (BHDs) and strong hypercapnic responses regarding the expiratory RA muscle, which is activated abruptly at higher BHDs in a person-specific range below 250 Hz and is dependent on the BHD. This is in contrast with recreational athletes, who had strong hypoxic responses regarding inspiratory IC muscle, which is activated faster and gradually in the frequency range of 250-450 Hz (independent of the person and BHD). This pilot study preliminarily indicates that it is possible to noninvasively assess the physiological characteristics of skeletal muscles, especially oxygenation, and improve physical fitness tests by determining the T-F features of elevated myoelectric IC and RA activity during BH.

Phrenic-to-intercostal reflex activity in response to high frequency spinal cord stimulation (HF-SCS)

ObjectiveHF-SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic-to-intercostal reflex during HF-SCS. MethodsIn 5 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the left and right external intercostal muscles (EI) in the 3rd interspace before and after sequential left and right phrenicotomy. ResultsMean control peak firing frequency of the right EI and left EI was 11.4 ± 0.3 Hz and 10.6 ± 0.3 Hz respectively. Following unilateral right phrenic nerve section, mean SMU peak firing frequency of right EI (ipsilateral to the section) was significantly greater when compared to control (15.9 ± 0.5 Hz vs 11.4 ± 0.3 Hz; p = 0.01). Mean SMU peak firing frequency of the contralateral left EI remained unchanged (10.2 ± 0.3 Hz vs 10.6 ± 0.3 Hz, p = 0.40). Subsequent, section of the left phrenic nerve resulted in significantly higher mean SMU peak firing frequency of the left EI (16.2 ± 0.5 Hz vs 10.2 ± 0.3 Hz) when compared to before section p = 0.01). Contralateral, right EI peak firing frequency was not different if compared to before left phrenic nerve section (16.9 ± 0.4 Hz vs. 15.9 ± 0.5 Hz; p = 0.14). ConclusionThis study demonstrates that during HF-SCS: 1) unilateral diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral EI muscles, 2) the neural circuitry mediating the phrenic-to-intercostal reflex is preserved at a spinal level and does not require supraspinal input and 3) unilateral compensatory increases were observed in EI muscle activation following ipsilateral diaphragm paralysis.

Model-Based Optimization of Spinal Cord Stimulation for Inspiratory Muscle Activation

ObjectiveHigh-frequency spinal cord stimulation (HF-SCS) is a potential method to provide natural and effective inspiratory muscle pacing in patients with ventilator-dependent spinal cord injuries. Experimental data have demonstrated that HF-SCS elicits physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways. However, the activation thresholds, extent of activation, and optimal electrode configurations (i.e., lead separation, contact spacing, and contact length) to activate these neural elements remain unknown. Therefore, the goal of this study was to use a computational modeling approach to investigate the direct effects of HF-SCS on the spinal cord and to optimize electrode design and stimulation parameters. Materials and MethodsWe developed a computer model of HF-SCS that consisted of two main components: 1) finite element models of the electric field generated during HF-SCS, and 2) multicompartment cable models of axons and motoneurons within the spinal cord. We systematically evaluated the neural recruitment during HF-SCS for several unique electrode designs and stimulation configurations to optimize activation of these neural elements. We then evaluated our predictions by testing two of these lead designs with in vivo canine experiments. ResultsOur model results suggested that within physiological stimulation amplitudes, HF-SCS activates both axons in the ventrolateral funiculi (VLF) and inspiratory intercostal motoneurons. We used our model to predict a lead design to maximize HF-SCS activation of these neural targets. We evaluated this lead design via in vivo experiments, and our computational model predictions demonstrated excellent agreement with our experimental testing. ConclusionsOur computational modeling and experimental results support the potential advantages of a lead design with longer contacts and larger edge-to-edge contact spacing to maximize inspiratory muscle activation during HF-SCS at the T2 spinal level. While these results need to be further validated in future studies, we believe that the results of this study will help improve the efficacy of HF-SCS technologies for inspiratory muscle pacing.

Evaluation of Loaded Breathing on Inspiratory Intercostal Muscle Activation During High Frequency Spinal Cord Stimulation to Restore Breathing in Spinal Cord Injury – Animal Model

BackgroundHigh Frequency Spinal Cord Stimulation (HF‐SCS) is a unique method of inspiratory muscle activation and has the potential to restore breathing in ventilator dependent tetraplegic subjects. However, these subjects are 3‐4 times more likely to have sleep disordered breathing (SDB) and have a higher incidence of obstructive airways disease than individuals in the general population, resulting in an increased inspiratory load.ObjectiveTo examine the effects of increased inspiratory load (airway occlusion) on inspiratory intercostal muscle activation during HF‐SCS.MethodsIn 3 spinalized (C2 level) anesthetized dogs, recording electrodes were positioned in the parasternal (PA) and external (EI) intercostal muscles (2nd and 3rd interspaces respectively) to record multiunit (integrated) and single motor units (SMU) EMG activities. During HF‐SCS at functional residual capacity (FRC), respiratory muscle activity was assessed before and after single and multi‐breath airway occlusion.ResultsDuring HF‐SCS, tracheal occlusion resulted in augmentation of peak multi‐unit integrated EI, but little change in PA EMG activity. During the occluded breath, EI activity increased to 148 ± 3% of that observed during control breaths (p<0.01) whereas PA activity was little changed (105 ± 5%; NS). EI instantaneous SMU peak firing frequency (PFF) was also greater during the occluded breath (15.7 ± 1.6Hz vs. 11.3 ± 0.3Hz; p<0.05). whereas there was only a small increase in PA PFF (10.8 ± 0.6Hz vs. 10.0 ± 0.6Hz; NS).SummaryHF‐SCS during airway occlusion results in significant increases in activation of the EI but not PA muscles.ConclusionHF‐SCS applied to support ventilation in high tetraplegics with airway obstruction may elicit compensatory increases in EI muscle activation. These results support the concept that spinal reflex effects remain functional during HF‐SCS. The EI have a much higher density of muscle spindles compared to the PA muscles, which may mediate the differential activation of these muscles.

Investigation of inspiratory intercostal muscle activity in patients with spinal cord injury: a pilot study using electromyography, ultrasonography, and respiratory inductance plethysmography.

[Purpose] The respiratory function in patients with cervical spinal cord injury is influenced by inspiratory intercostal muscle function. However, inspiratory intercostal muscle activity has not been conclusively evaluated. We evaluated the inspiratory intercostal muscle activity in patients with cervical spinal cord injury by using inspiratory intercostal electromyography, respiratory inductance plethysmography, and ultrasonography. [Participants and Methods] Three patients with cervical spinal cord injury were assessed. The change in mean amplitude (rest vs. maximum inspiration) was calculated by using intercostal muscle electromyography. Changes in intercostal muscle thickness (resting expiration and maximum inspiration) were also evaluated on ultrasonography. The waveform was converted to spirometry ventilation with respiratory inductance plethysmography, and the waveform at the xiphoid was considered to determine the rib cage volume. Each index was compared with the inspiratory capacities in each case. [Results] Intercostal muscle electromyography failed to measure the notable myoelectric potential in all the patients. The rib cage volume was higher at higher inspiratory capacities. The changes in muscle thickness were not significantly different between the patients. [Conclusion] The rib cage volume (measured with inductance plethysmography) was greater in the patients with cervical spinal cord injury when inspiratory intercostal muscle activity was high. Respiratory inductance plethysmography can capture inspiratory intercostal muscle function in patients with cervical spinal cord injury.

Comparison of Wire and Disc Leads to Activate the Inspiratory Muscles in Dogs

ObjectiveHF‐SCS is a unique method of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury (SCI). The purpose of the present study was to examine the effectiveness of wire leads, which can be placed using minimally invasive techniques, to activate the inspiratory muscles.MethodsIn 5 anesthetized dogs, in separate trials, disc and wire leads were inserted onto the ventral epidural space at the T1–T4 spinal cord levels. The effects of electrical stimulation with disc, single wire, and two wire leads placed in parallel were compared.Outcome measuresAirway pressure generation following stimulation with disc and various configurations of wire leads were compared.ResultsSeveral different configurations of wire leads resulted in airway pressures that were similar to those generated with monopolar stimulation with disc leads (D). For example, monopolar stimulation (3mA, 300Hz, 0.2ms) with parallel wire leads in which each of the electrode contacts at the T2 were connected together and functioned as a common cathode (Y‐connection) and monopolar stimulation (separate cathode) at T2 both with a remote ground resulted in airway pressures that were 91±6 and 92±4%, respectively, of those achieved with D (NS for both). Bipolar stimulation (3mA, 300Hz, 0.2ms) with parallel wire leads using Y‐connection and with a separate cathode at the T2 and T3 level resulted in airway pressures that were 96 ± 4 and 94 ± 4%, respectively, of the pressures achieved with D (NS for both).ConclusionThese results suggest that specific configurations of wire leads, which can be placed via minimally invasive techniques, result in comparable activation of the inspiratory muscles compared to disc leads and may be a useful technique to restore ventilatory support in persons with SCI.Support or Funding InformationSupportNIH‐NINDS (R01NS064157)DisclosureDr. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems and holds patents for spinal cord stimulation to restore cough and respiration (5,678,535; 5,911,218; 5,999,855; 8,751,004). Drs. DiMarco and Kowalski hold the U.S. patents for technology related to the content of this manuscript: Respiratory Muscle Activation by Spinal Cord Stimulation (8,352,036).

A Computational Model of Upper Thoracic High‐Frequency Spinal Cord Stimulation to Optimize Inspiratory Muscle Activation

BackgroundHigh‐frequency spinal cord stimulation (HFSCS) has been previously shown to elicit physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways in canines. It was previously hypothesized that during upper thoracic HF‐SCS, the phrenic motoneuron pools are activated via spinal pathways located in the ventro‐lateral funiculus (VLF).ObjectiveThe aim of the present study was to develop a computational model of ventral HFSCS to optimize stimulation parameters and electrode configurations for activation of the inspiratory muscles.MethodsWe created a computer model of an anatomically‐accurate finite element model (FEM) of the canine spinal cord and surrounding anatomy, along with an implanted HFSCS electrode array. From this FEM, we calculated extracellular voltages generated by SCS and applied them to multicompartment cable models of axons within the VLF. Model analysis compared activation thresholds for several unique electrode designs, configurations, and electrode placements in order to optimize activation of these VLF fibers to maximize inspiratory muscle activation.ResultsFor initial model parameterization, we performed experimental measurements testing various electrode configurations and designs. We then used our computer model to evaluate several additional stimulation configurations (e.g. monopolar, bipolar) on VLF fiber selectivity. We then evaluated the effect of wider or narrow lateral lead spacing, contact spacing, and contact size. Finally, we considered several SCS waveform settings, such as rectangular waveforms and ramped waveforms, to potentially generate muscle activation more similar to natural inspiration.ConclusionsWe used our model to optimize electrode configurations, placements and novel stimulation waveforms of HFSCS to target fibers within the VLF. In particular, we found that wider lateral spacing between percutaneous electrodes better targets VLF fibers as opposed to the narrower spacing initially tested. We also show that ramped stimulation slowly recruits VLF fibers over time, which could improve naturalistic inspiratory muscle activation. In future work, we will perform experimental measurements in an animal model of HFSCS to confirm the ability of these optimized electrode designs and waveform parameters to better recreate normal inspiration.DisclosureDr. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems and holds patents for spinal cord stimulation to restore cough and respiration (5,678,535; 5,911,218; 5,999,855; 8,751,004). Drs. DiMarco and Kowalski hold the U.S. patents for technology related to the content of this manuscript: Respiratory Muscle Activation by Spinal Cord Stimulation (8,352,036).Support or Funding InformationThis work is supported by NIH‐NINDS (R01NS064157).

Intractable hiccups (Singultus) of psychogenic origin- a case report.

Hiccups are repeated involuntary, intermittent spasmodic contractions of the diaphragm and inspiratory intercostal muscles that results in sudden inspiration followed by a sudden closure of the glottis. It is naturally benign, self-limited but may be most of the time organic in nature and in some cases chronic, debilitating and psychogenic. Here we report a case of a 16 year old female student who developed hiccups of a psychogenic origin started by stress, which lasted for more than weeks sometime for a month and is successfully treated by antipsychotics haloperidol and psychological interventions. Physicians always face a diagnostic challenge, especially when no identifiable organic cause is elicited. However, such cases are invariably referred for psychiatric evaluation and treatment.

Phrenic‐to‐Intercostal Reflex Activity in Response to High Frequency Spinal Cord Stimulation (HF‐SCS)

ObjectiveHF‐SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic to intercostal reflex during HF‐SCS.MethodsIn 3 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level before and after cervical phrenicotomy. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the external intercostal muscles before and after phrenicotomy.ResultsFollowing unilateral phrenic nerve section, mean peak SMU firing frequency of EI ipsilateral to the section was significantly greater when compared to control (15.9±0.7 vs. 12.1±0.5 Hz, p<0.05). However, mean peak SMU firing frequency of the contralateral EI was unchanged (11.1±0.4 vs. 12±0.4 Hz, NS). Section of the contralateral phrenic nerve results in significantly higher mean peak SMU firing frequency of the contralateral EI (15.9±0.7 Hz, p<0.05) when compared to before section.ConclusionThis study demonstrates that during HF‐SCS after C2 spinalization: 1) diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral external intercostal muscles, and 2) the neural circuitry mediating the phrenic‐to‐intercostal reflex is preserved at a spinal level. Consequently, HF‐SCS applied to support ventilation in high tetraplegics with unilateral phrenic nerve injury may elicit increased activity of ipsilateral inspiratory intercostal muscles.Support or Funding InformationSupport: NIH‐NINDS (R01NS064157) and MetroHeath FoundationDisclosure: Dr. DiMarco is a Founder of and has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Risperidone-Induced Hiccups in an Adolescent

Hiccups are involuntary spasmodic contractions of the diaphragm and inspiratory intercostal muscles followed by sudden closure of glottis which leads to halting the start of an inspiration. There are many factors which may cause hiccups. Although the exact pathophysiological processes involved have not yet been established, the neurotransmitters dopamine, serotonin and gamma amino butyric acid (GABA) have been documented to play a significant role in the generation of hiccups. Here, we present a case of risperidone-induced hiccups in a 14-year old adolescent to discuss the probable causes, the etiology and the clinical outcomes of this side effect.

Distribution of respiration-related neuronal activity in the thoracic spinal cord of the neonatal rat: An optical imaging study

The inspiratory motor outputs are larger in the intercostal muscles positioned at more rostral segments. To obtain further insights into the involvement of the spinal interneurons in the generation of this rostrocaudal gradient, the respiratory-related neuronal activities were optically recorded from various thoracic segments in brainstem–spinal cord preparations from 0- to 2-day-old rats. The preparation was stained with a voltage-sensitive dye, and the optical signals from about 2.5s before to about 7.7s after the peak of the C4 inspiratory discharge were obtained. Respiratory-related depolarizing signals were detectable from the ventral surface of all thoracic segments. Since the local blockage of the synaptic transmission in the thoracic spinal cord induced by the low-Ca2+ superfusate blocked all respiratory signals, it is likely that these signals came from spinal neurons. Under the-low Ca2+ superfusate, ventral root stimulation, inducing antidromic activation of motoneurons, evoked depolarizing optical signals in a restricted middle area between the lateral edge and midline of the spinal cord. These areas were referred to as ‘motoneuron areas’. The respiratory signals were observed not only in the motoneuron areas but also in areas medial to the motoneuron areas, where interneurons should exist; these were referred to as ‘interneuron areas’. The upper thoracic segments showed significantly larger inspiratory-related signals than the lower thoracic segments in both the motoneuron and interneuron areas. These results suggest that the inspiratory interneurons in the thoracic spinal cord play a role in the generation of the rostrocaudal gradient in the inspiratory intercostal muscle activity.

Daily acute intermittent hypoxia elicits functional recovery of diaphragm and inspiratory intercostal muscle activity after acute cervical spinal injury

A major cause of mortality after spinal cord injury is respiratory failure. In normal rats, acute intermittent hypoxia (AIH) induces respiratory motor plasticity, expressed as diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF). Dia (not T2 EIC) LTF is enhanced by systemic adenosine 2A (A2A) receptor inhibition in normal rats. We investigated the respective contributions of Dia and T2 EIC to daily AIH-induced functional recovery of breathing capacity with/without A2A receptor antagonist (KW6002, i.p.) following C2 hemisection (C2HS). Rats received daily AIH (dAIH: 10, 5-min episodes, 10.5% O2; 5-min normoxic intervals; 7 successive days beginning 7days post-C2HS) or daily normoxia (dNx) with/without KW6002, followed by weekly (reminder) presentations for 8weeks. Ventilation and EMGs from bilateral diaphragm and T2 EIC muscles were measured with room air breathing (21% O2) and maximum chemoreceptor stimulation (MCS: 7% CO2, 10.5% O2). dAIH increased tidal volume (VT) in C2HS rats breathing room air (dAIH+vehicle: 0.47±0.02, dNx+vehicle: 0.40±0.01ml/100g; p<0.05) and MCS (dAIH+vehicle: 0.83±0.01, dNx+vehicle: 0.73±0.01ml/100g; p<0.001); KW6002 had no significant effect. dAIH enhanced contralateral (uninjured) diaphragm EMG activity, an effect attenuated by KW6002, during room air breathing and MCS (p<0.05). Although dAIH enhanced contralateral T2 EIC EMG activity during room air breathing, KW6002 had no effect. dAIH had no statistically significant effects on diaphragm or T2 EIC EMG activity ipsilateral to injury. Thus, two weeks post-C2HS: 1) dAIH enhances breathing capacity by effects on contralateral diaphragm and T2 EIC activity; and 2) dAIH-induced recovery is A2A dependent in diaphragm, but not T2 EIC. Daily AIH may be a useful in promoting functional recovery of breathing capacity after cervical spinal injury, but A2A receptor antagonists (e.g. caffeine) may undermine its effectiveness shortly after injury.

Mechanism of the increased rib cage expansion produced by the diaphragm with abdominal support.

When the abdomen in quadriplegic subjects is given a passive mechanical support, the expansion of the lower rib cage during inspiration is greater and the inward displacement of the upper rib cage is smaller. These changes have traditionally been attributed to an increase in the appositional force of the diaphragm, but the mechanisms have not been assessed. In this study, the inspiratory intercostal muscles in all interspaces were severed in anesthetized dogs, so that the diaphragm was the only muscle active during inspiration, and the displacements of the ribs 10 and 5 and the changes in pleural and abdominal pressure were measured during unimpeded breathing and during breathing with a plate applied on the ventral abdominal wall. In addition, external forces were applied to the 10th rib pair in the cranial and lateral directions, and the rib trajectories thus obtained were used as the basis for a vector analysis to estimate the relative contributions of the insertional and appositional forces to the rib 10 displacements during breathing. Application of the abdominal plate caused a marked increase in the inspiratory cranial and outward displacement of rib 10 and a decrease in the inspiratory caudal displacement of rib 5. Analysis of the results showed, however, that 1) the insertional and appositional forces contributed nearly equally to the increased inspiratory displacement of rib 10 and 2) the decrease in the expiratory displacement of rib 5 was the result of both the greater displacement of the lower ribs and the decrease in pleural pressure.

Action of the isolated canine diaphragm on the lower ribs at high lung volumes.

The normal diaphragm has an inspiratory action on the lower ribs, but subjects with chronic obstructive pulmonary disease commonly have an inward displacement of the lateral portions of the lower rib cage during inspiration. This paradoxical displacement, conventionally called 'Hoover's sign', has traditionally been attributed to the direct action of radially oriented diaphragmatic muscle fibres. In the present study, the inspiratory intercostal muscles in all interspaces in anaesthetized dogs were severed so that the diaphragm was the only muscle active during inspiration. The displacements of the lower ribs along the craniocaudal and laterolateral axes and the changes in pleural pressure (∆Ppl) and transdiaphragmatic pressure were measured during occluded breaths and mechanical ventilation at different lung volumes between functional residual capacity (FRC) and total lung capacity. From these data, the separate effects on rib displacement of ∆Ppl and of the force exerted by the diaphragm on the ribs were determined. Isolated spontaneous diaphragm contraction at FRC displaced the lower ribs cranially and outward, but this motion was progressively reversed into a caudal and inward motion as lung volume increased. However, although the force exerted by the diaphragm on the ribs decreased with increasing volume, it continued to displace the ribs cranially and outward. These observations suggest that Hoover's sign is usually caused by the decrease in the zone of apposition and, thus, by the dominant effect of ∆Ppl on the lower ribs, rather than an inward pull from the diaphragm.

Ipsilateral inspiratory intercostal muscle activity after C2 spinal cord hemisection in rats

BackgroundUpper cervical spinal cord hemisection causes paralysis of the ipsilateral hemidiaphragm; however, the effect of C2 hemisection on the function of the intercostal muscles is not clear. We hypothesized that C2 hemisection would eliminate inspiratory intercostal activity ipsilateral to the injury and that some activity would return in a time-dependent manner.MethodsFemale Sprague Dawley rats were anesthetized with urethane and inspiratory intercostal electromyogram (EMG) activity was recorded in control rats, acutely injured C2 hemisected rats, and at 1 and 16 weeks post C2 hemisection.ResultsBilateral recordings of intercostal EMG activity showed that inspiratory activity was reduced immediately after injury and increased over time. EMG activity was observed first in rostral spaces followed by recovery occurring in caudal spaces. Theophylline increased respiratory drive and increased intercostal activity, inducing activity that was previously absent.ConclusionThese results suggest that there are crossed, initially latent, respiratory connections to neurons innervating the intercostal muscles similar to those innervating phrenic motor neurons.

Novel Use of Chicory for the Treatment of Hiccups in Liver Obstruction: In Iranian Traditional Medicine

Dear Editor, A hiccup is the result of an involuntary, intermittent spasmodic contraction of the diaphragm and the inspiratory intercostal muscles. Based on Iranian Traditional Medicine, hiccups are stomach diseases and movements in the stomach with the combination of spasmodic contraction followed by a stretching distention (1). Although hiccups may be a temporary action which need no treatment, sometimes a refractory hiccup would be disturbing to a normal life. According to Avicenna, a hiccup may occur due to different causes, one of which occurs because of liver obstruction. We experienced the successful use of Chicory to cure two cases of hiccups caused by liver obstruction and inflammation in digestion Clinic of Shahid Beheshti Medical Faculty. The first case was a 78 year old male with two years of refractory and chronic hiccup, who was under a common drug treatment. Due to his refusal in using the drugs because of their side effects, his hiccups were continuous and loud enough to disturb his sleep, eating routines. It also was so severe that made him depressed. Other symptoms included pains and heaviness in RUQ. These two symptoms based on Avicenna are Pathgnomonic of liver obstruction. This was resolved by one dose of 10% syrup of Chicory, which was orally taken. It was used for three weeks before breakfast. In the middle of the second week, his problem was slighter so that it was completely gone by the end of third week. The subject was under control for six months. The problem appeared again at the end of the third month, so we started the same treatment. By the end of the sixth months, he never complained. The other patient was a 54 year old male with an intermittent hiccup, which occurred almost every day, worsening lately. He had been under medical treatment; however, his hiccups were not completely cured. The same treatment was prescribed to him in three weeks and after the 2nd week, the hiccup was resolved and there was seen no relapse within six months of control. In the Allopathic medicine hiccup etiology is not pretty clear. As far as it is known hiccups are caused by various factors such as neurologic or non-neurologic agents, cerebral tumors, prostate cancer, abdomen surgery, MI, hepatitis, gastritis, duodenitis, esophageal reflux, peptic ulcer, and esophagitis (2-4). To cure a hiccup, in the Allopathic medicine metoclopramide, chlorpromazine, baclofen, gabapentin, Phernic nerve neurolysis, and nerve blocks are used (2, 4). The best result was obtained by using Gabapentin in acute cases. In Traditional medicine, which goes back to Hippocrates, BC 460 hiccups are sometimes defined as a symptom of prognosis and it has been also mentioned that if hiccups are accompanied with red eyes, it indicates bad prognosis which can be indicative of encephalitis, gastritis, and neuritis attaching stomach and brain (1, 5). In Avicenna's view, hiccups are known as stomach diseases. He relates it to the cardia of stomach. Hiccups sometimes happen due to the interaction between stomach and diseases in other organs such as hepatitis and liver obstruction. In this study we investigated those hiccups caused by liver disease (5). Chicory belongs to the Composite family with the scientific name of Chicorium Intybus L. which is used as Diuretic, appetizer, and cholagogue (6-8). In ITM (Iranian Traditional Medicine), Chicory is known as Handba and is an Opener that is the literal translation for MOFATTEH. It is bile and blood intensity and Heddat (Acuity) reliever, and its root is deeply opener and MOLATTEF (to dilute dense humor with moderate heat) of humors (3). It is also useful for refining blood and swelling organs. Its usage dose is from 4 to 12 grams (9). Considering the weak effects of chemical drugs on treatment of refractory hiccups and their side effects, Chicory which was also proved useful in this study with no recorded side effect, (10) is recommended as an appropriate treatment for chronic hiccups caused by liver disease.

Aripiprazole induced hiccups

Hiccups are a product of involuntary, intermittent spasmodic contraction of the diaphragm and inspiratory intercostal muscles that results in sudden inspiration and abrupt closure of the glottis. The exact pathophysiology of hiccups remains unknown. However, certain neurotransmitters, medications, and other factors have been implicated. We report a case of a 38 year old patient who developed hiccups three days after adding aripiprazole 5 mg once a day to his medication regimen. Medical and environmental causes were ruled out and aripiprazole was discontinued. One day later, the hiccups resolved. Several case reports have described patients who developed hiccups when treated with aripiprazole and related this to changes in neurotransmitter concentrations. However, due to limited literature, it was difficult to determine rate of occurrence of this adverse event with aripiprazole. A temporal but not a causal relationship was observed between initiating aripiprazole and development of hiccups in this patient. A causal relationship cannot be established since the patient was not re-challenged with aripiprazole. Nonetheless, clinicians should be cognizant that use of aripiprazole may be associated with hiccups.

Effects of the insertional and appositional forces of the canine diaphragm on the lower ribs.

The diaphragm has an inspiratory action on the lower ribs, and current conventional wisdom maintains that this action is the result of two mechanisms, namely, the force applied by the muscle fibres on the ribs into which they insert (insertional force) and the transmission of abdominal pressure through the zone of apposition (appositional force). The magnitude of the diaphragmatic force and the relative contributions of the insertional and appositional components, however, are unknown. To assess these forces, the inspiratory intercostal muscles in all interspaces were severed in anaesthetized dogs, so that the diaphragm was the only muscle active during inspiration, and the displacements of the lower ribs along the craniocaudal and laterolateral axes were measured during quiet breathing, during occluded breaths and during passive lung inflation. From these data, the isolated effects of pleural pressure and transdiaphragmatic pressure on rib displacement were determined. Then external forces were applied to the ribs in the cranial and the lateral direction to simulate, respectively, the effects of the insertional and appositional forces, and the rib trajectories for these external forces were used as the basis for a vector analysis to obtain the relative magnitudes of the insertional and appositional contributions to the rib displacement driven by transdiaphragmatic pressure. The results show that, per unit pressure, the inspiratory effect of the diaphragmatic force on the lower ribs is equal to the expiratory effect of pleural pressure, and that the insertional force contributes 60% of that inspiratory effect.

INSPIRATORY INTERCOSTAL LONG TERM FACILITATION IN UNANESTHETIZED RATS

Moderate acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long‐term facilitation (LTF). AIH‐induced LTF is most frequently observed as a persistent increase in phrenic motor output (phrenic long term facilitation, pLTF), diaphragm activity (diaphragm long term facilitation, diaLTF) or ventilation (ventilatory LTF). Since little is known concerning the potential contributions of accessory inspiratory pump muscles to ventilatory LTF, we investigated the effects of AIH on respiratory activity in the second external intercostal muscle (T2 EIM) in unanesthetized Sprague Dawley rats. Rats were instrumented to enable chronic EMG telemetry from the right T2 EIM and diaphragm. Diaphragm and T2 EIM EMG activities were measured before (60 min), during, and after AIH (10, 5‐min hypoxic episodes, 10.5% O2; 5 min normoxic intervals; n = 8) or time control (continuous normoxia, n = 6). Integrated Dia (22.1 ± 6.6% p &lt; 0.05) and T2 EIM burst amplitude (42.6 ± 3.5 % p &lt;0.05) were significantly increased 60 min post‐AIH; thus EIM LTF is relatively greater than diaLTF in unanesthetized rats. Respiratory frequency (15 ± 2.7%; p &lt; 0.05) and external intercostal minute activity (activity × frequency; 64.1 ± 5.7%, p &lt; 0.05) were also significantly elevated 60 min post‐AIH. TC did not induce diaLTF or EIM LTF. Thus, inspiratory intercostal muscles express greater capacity for AIH‐induced plasticity versus the diaphragm. An understanding of AIH induced respiratory plasticity may inspire development of new therapeutic strategies to treat conditions causing respiratory insufficiency, such as cervical spinal injury. Supported by NIH HL69064 and HL80209.

Function of the canine inspiratory muscle pump in pleural effusion: influence of body position

Pleural effusion, a complicating feature of many diseases of the lung and pleura, adversely affects the pressure-generating capacity of the diaphragm in supine dogs. The objective of the present study was to assess the impact of body position on this effect and to evaluate the adaptation to effusion of the inspiratory muscle pump during breathing. Two experiments were performed. In the first, progressively increasing effusion was induced in anesthetized animals, and the changes in pleural (ΔPpl) and abdominal (ΔPab) pressure were measured during isolated phrenic nerve stimulation while the animals were placed in both the supine and the 45° head-up posture. In the second experiment, graded pleural effusion was also performed, and ΔPpl, ΔPab, and the electromyogram of the parasternal intercostal muscles were measured while the vagotomized animals were breathing spontaneously in the same two postures. The data showed that with effusion 1) ΔPpl during phrenic nerve stimulation was substantially lower with the animals in the head-up than in the supine posture; 2) this postural effect was primarily the result of the decrease in muscle length in the head-up posture; 3) during spontaneous breathing, however, parasternal intercostal inspiratory activity increased and ΔPpl remained unaltered while ΔPab decreased; and 4) the decrease in ΔPab and in the ΔPab/ΔPpl ratio was much larger in the head-up than in the supine posture. It is concluded that in the presence of pleural effusion, the pressure contribution of the inspiratory intercostal muscles during breathing increases and compensates for the shortening of the diaphragm, particularly in the upright posture.