Diaphragm activation with intramuscular stimulation in dogs

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.     

Diaphragm EMG measured by cervical magnetic and electrical phrenic nerve stimulation

The purpose of the study was to compare electrical stimulation (ES) and cervical magnetic stimulation (CMS) of the phrenic nerves for the measurement of the diaphragm compound muscle action potential (CMAP) and phrenic nerve conduction time. A specially designed esophageal catheter with three pairs of electrodes was used, with control of electrode positioning in 10 normal subjects. Pair A and pair B were close to the diaphragm (pair A lower than pair B); pair C was positioned 10 cm above the diaphragm to detect the electromyogram from extradiaphragmatic muscles. Electromyograms were also recorded from upper and lower chest wall surface electrodes. The shape of the CMAP measured with CMS (CMS-CMAP) usually differed from that of the CMAP measured with ES (ES-CMAP). Moreover, the latency of the CMS-CMAP from pair B (5.3 +/- 0.4 ms) was significantly shorter than that from pair A (7.1 +/- 0.7 ms). The amplitude of the CMS-CMAP (1.00 +/- 0.15 mV) was much higher than that of ES-CMAP (0.26 +/- 0.15 mV) when recorded from pair C. Good-quality CMS-CMAPs could be recorded in some subjects from an electrode positioned very low in the esophagus. The differences between ES-CMAP and CMS-CMAP recorded either from esophageal or chest wall electrodes make CMS unreliable for the measurement of phrenic nerve conduction time.     

Intestinal permeability and inflammation in patients on NSAIDs

PURPOSE: The purpose of this study was to determine whether high frequency fatigue was present in the diaphragm after intense whole body endurance exercise. METHODS: We used bilateral phrenic nerve stimulation (BPNS) before and during recovery from whole body exercise to detect fatigue in the diaphragm. To detect high frequency fatigue we used paired stimuli at 10, 20, 50, 70, and 100 Hz frequency and determined the transdiaphragmatic pressure (Pdi) response to the second stimulation (T2). RESULTS: The subjects (N = 10) exercised at 93.3 +/- 2.3% of their VO2max for 9.9 +/- 0.5 min. The Pdi response to "twitch" and 10 Hz "tetanic" stimulation was decreased immediately after exercise versus pre-exercise values (-23.4 +/- 3.3%). The T2 amplitude was substantially reduced at all frequencies immediately after exercise (-28.0%), but by 30 min into recovery the T2 amplitude at 70 and 100 Hz was not different from pre-exercise values. In contrast, at 10 and 20 Hz the T2 response was still significantly reduced. CONCLUSIONS: We interpret these data to mean that high frequency fatigue as well as low frequency fatigue were present in the diaphragm after intense whole body endurance exercise.     

Human respiratory muscles: sensations, reflexes and fatiguability

1. Given the importance of the ventilatory 'pump' muscles, it would not be surprising if they were endowed with both sensory and motor specializations. The present review focuses on some unexpected properties of the respiratory muscle system in human subjects. 2. Although changes in blood gas tension were long held not to influence sensation directly, studies in subjects who are completely paralysed show that increases in arterial CO2 levels elicit strong sensations of respiratory discomfort. 3. Stretch reflexes in human limb muscles contain a monosynaptic spinal excitation and a long-latency excitation. However, inspiratory muscles show an initial inhibition when tested with brief airway occlusions during inspiration. This inhibition does not depend critically on input from pulmonary or upper airway receptors. 4. Human inspiratory muscles (including the diaphragm) have been considered to fatigue during inspiratory resistive loading. However, recent studies using phrenic nerve stimulation to test the force produced by the diaphragm show that carbon dioxide retention (hypoventilation) and voluntary cessation of loading occur before the muscles become overtly fatigued.     

Automated Testing System for Overhead Line Cables

An automated testing system for overhead line cables with temperature control from environment temperature to 200°C is presented. The aim of the test is to determine mechanical characteristics such as creep, thermal strain, stress∕strain, fatigue, and self-damping in order to improve the design of overhead lines through the analysis of new and already-in-use cables, as well as quality control. The data are obtained through the utilization of displacement, temperature, and load sensors. The temperature and the cable tension are continuously controlled. The data acquisition, analysis, and feedback are made through an intelligent interface. The maximum load is 200 kN.     

Hydroxylation of salicylate by the in vitro diaphragm: evidence for hydroxyl radical production during fatigue

There is increasing evidence that oxygen-derived free radicals produced during strenuous work by the diaphragm may contribute to diaphragm fatigue and/or injury. However, the precise identity of these oxygen radicals remains unknown, inasmuch as oxygen free radicals are extremely short lived and their detection in biologic systems is quite difficult. There is recent evidence that the salicylate-trapping method may be a useful means of monitoring tissue production of hydroxyl radical (.OH). This method is predicated on the fact that salicylate's phenolic ring can be attacked by .OH at the 3 or 5 position to yield 2,3- or 2,5-dihydroxybenzoic acid (DHB). These metabolites are stable and can be identified by high-performance liquid chromatography (HPLC) coupled with electrochemical or ultraviolet detection. To test the hypothesis that hydroxylated salicylates are produced during diaphragm fatigue, we exposed in vitro rat diaphragm strips to a physiological saline solution containing 2.0 mM sodium salicylate for approximately 15 min. The solution was then removed, and the strips were fatigued (20 Hz, 200-ms train duration, 1 train/s) via phrenic nerve stimulation for 30 s-10 min. The diaphragm strips were subsequently homogenized, and the homogenate was analyzed by HPLC coupled with ultraviolet detection. Levels of 2,3-DHB were significantly higher in fatigued than in control nonfatigued strips. There was also a significant correlation between the amount of 2,3-DHB in the fatigued muscle and the accumulated tension-time product developed during fatigue. 2,5-DHB was not consistently identified in control or experimental strips.(ABSTRACT TRUNCATED AT 250 WORDS)     

Release of thiamine and formation of a methylthiamine-like substance in the phrenic nerve-diaphragm preparation of the rat

An increased formation of a radioactive methylthiamine-like substance (MTLS) in the end plate region of the rat diaphragm muscle and a release of radioactivity chromatographed as thiamine into the bath medium after a subcutaneous injection of 35S-thiamine were found after stimulation of the phrenic nerve. There was also an increased formation of the radioactive methylthiamine-like substance in the denervated diaphragm preparation incubated with radioactive acetylcholine (ACh) in comparison with the innervated diaphragm.     

Effect of free radical scavengers on diaphragmatic fatigue

Recent studies have suggested that free radical scavenger administration reduces the rate of development of diaphragm fatigue. Much of this work has been done, however, using in vitro muscle preparations; the purpose of the present study was to assess the effect of scavengers on in vivo diaphragm contractile function. To accomplish this, we compared the rate of development of fatigue of the electrically stimulated diaphragm in four groups of dogs: (1) animals given intravenous polyethylene glycol adsorbed superoxide dismutase (PEG-SOD, 2,000 units/kg) 1 h before a fatigue trial; (2) a group given intravenous dimethylsulfoxide (DMSO, 0.5 ml/kg of a 50% solution) before fatigue; (3) a group given saline before fatigue; and (4) a group treated with denatured PEG-SOD (2,000 units/kg) before fatigue. We measured diaphragmatic concentrations of thiobarbituric acid reactive substances (TBAR), a marker of free radical-mediated lipid peroxidation, on muscle samples taken at the conclusion of fatigue trials. As a control, we also measured TBAR concentrations for muscle samples taken from nonfatigued diaphragm. We found that the rate of development of diaphragm fatigue was much greater in saline and denatured PEG-SOD-treated groups than for animals pretreated with either PEG-SOD or DMSO, with force falling to 23 +/- 4, 21 +/- 4, 50 +/- 7, and 47 +/- 6% of its initial value, respectively, over a 2-h period of electrophrenic stimulation in these four groups of animals (p < 0.01). TBAR concentrations in fatigued diaphragm from saline and denatured PEG-SOD-treated animals were significantly higher than levels for either nonfatigued fresh diaphragm or fatigued diaphragm taken from PEG-SOD- or DMSO-treated animals (p < 0.01). These data suggest that diaphragm fatigue resulting from repetitive low-frequency stimulation is associated with lipid peroxidation within this muscle and that pretreatment with free radical scavengers prevents lipid peroxidation and reduces the rate of development of fatigue.     

The nucleus is the target for radiation-induced chromosomal instability

Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.     

Right hemidiaphragmatic twitching: a complication of bipolar atrial pacing

A patient with an atrioventricular sequential pacemaker developed rhythmic contractions of the right hemidiaphragm. This was found to be the result of right phrenic nerve stimulation, which was directly related to the wide distance between the poles of an ELA atrial lead when pacing in bipolar mode. Pole separation in current atrial leads is discussed.     

Percutaneous repair of a traumatic bile duct laceration in a liver transplant allograft

BACKGROUND: Phrenic nerve palsy in infants and young children usually results from birth injury or iatrogenic damage. The newborn almost invariably presents with severe respiratory distress, diaphragmatic elevation, and paradoxical movement at the affected side. METHODS/RESULTS: In this retrospective analysis a group of 23 patients below the age of 1 year with an obstetric or postoperative phrenic nerve injury was studied and compared with cases in the literature. All patients were admitted between 1986 and 1997 to the Pediatric Surgical Center, Amsterdam. Thirteen of 18 patients with an obstetric phrenic nerve injury underwent plication of the diaphragm after an average observation period of 100 days. In the remaining five children with an obstetric phrenic nerve injury, spontaneous recovery appeared within 1 month. Only one of five patients with a phrenic nerve palsy after a cardiac surgical procedure underwent plication of the diaphragm. Fifteen of the 34 patients described in the literature underwent plication of the diaphragm after an average of 54 days. CONCLUSIONS: If after 1 month no spontaneous recovery of the diaphragmatic paralysis caused by a phrenic nerve injury occurs, plication of the diaphragm is indicated. This operation proved to be successful for relief of symptomatic phrenic nerve injury in all cases. If the condition of the patient clinically deteriorates during this first month of life, the patient should be operated on immediately.     

Paired phrenic nerve stimuli for the detection of diaphragm fatigue in humans

The transdiaphragmatic pressure (Pdi) elicited by paired bilateral phrenic nerve stimulation may be viewed as the sum of the Pdi values produced by the first (t1) and second (t2) stimulus. The Pdi at t2 (P[di,t2]) is a function of the interstimulus interval. A reduction in the ratio obtained by dividing Pdi,t2 at 10 Hz (P[di,t2,10]) by Pdi at 100 Hz (P[di,t2,100]) (t2(10:100)) has been proposed as a test of low frequency diaphragm fatigue. The aim of the present study was to establish whether this change could also be detected using paired cervical magnetic nerve stimulation (pCMS), and whether t2(10:100) was influenced by lung volume. We studied healthy subjects at functional residual capacity (FRC), at 0.5 and 1.0 L below FRC, and at 0.5, 1.0 and 1.5 L above FRC. The subjects were then subjected to a fatiguing protocol (2 min of maximal isocapnic ventilation (MIV)). Studies were repeated at FRC 20 and 60 min after MIV and between these times at 1.0 L below and 1.5 L above FRC. In the unfatigued state, t2(10:100) had a negative relationship with increasing lung volume (r2=0.98, p=0.002). After MIV there was a fall in the Pdi elicited by a single stimulus (mean fall at 20 min 17.9% and at 60 min 14.6%, p<0.03 for both). t2(10:100) fell by a mean 28.1% after 20 min and mean 22.9% at 60 min (p<0.03 for both). This change was mainly mediated by a fall in the P[di,t2,10]. The t2(10:100) was not able to distinguish between fatigue and acute hyperinflation. We conclude that paired cervical magnetic nerve stimulation may be used to detect low frequency diaphragm fatigue but that it remains important to control for lung volume.     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.     

An integrated dual sensor system automatically optimized by target rate histogram

The use of combined sensors and advanced algorithms using different principles can improve rate performance over a single sensor system. Combinations of sensors and more sophisticated algorithms, however, invariably increase the complexity of pacemaker programming. An automatically optimized combined minute ventilation and activity DDDR pacemaker was developed to minimize repeated sensor adjustment. The device used subthreshold (below cardiac stimulation threshold) lead impedance to detect lead configuration at implantation automatically, followed by "implant management," including setting of lead polarity and initiation of DDDR pacing. Automatic sensor adaptation was achieved by programming a "target rate histogram" based on the patient's activity level and frequency of exertion, and the rate profile optimization process matched the recorded integrated sensor response to the target rate histogram profile. In nine patients implanted with the DX2 pacemakers, the implant management gave 100% accuracy in the detection of lead polarity. Rate profile optimization automatically increased the pacing rate during exercise between discharge and 3-month follow-up (hall walk: 78 +/- 3 vs 98 +/- 3 beats/min, and maximal treadmill exercise: 89 +/- 6 vs 115 +/- 5 beats/min, P < 0.001) with a significant increase in exercise duration during maximal exercise (7.18 +/- 1 min vs 9.56 +/- 2 min, P = 0.05). The accuracy of rate profile optimization versus manual programming was assessed at 1 month, and there was no significant difference between pacing rate kinetics and maximal pacing rate between the two methods of programming. In conclusion, pacemaker automaticity can be initiated at implantation and the self-optimized rate adaptive response appeared to be comparable to that derived from a manual programming procedure, which may reduce the need to perform time consuming sensor programming.     

2D Measurements of Magnetic Field near an Oscillating Interface between Two Fluids Carrying an Electrical Current

An experimental technique is presented to measure two‐dimensional magnetic fields outside a cylindrical cell containing two electrically conducting fluids as the primary step of magnetic field tomography (MFT). The magnetic field is induced by a direct current through the fluids. Under a periodic, vertical vibration driven by a pneumatic shaker, Faraday instabilities are generated, which lead to a series of non‐axisymmetrical wave modes, and the non‐axisymmetrical interface shape introduces a perturbation to the magnetic field which can be measured by eight two‐dimensional fluxgate sensors fixed concentrically and uniformly around the cell. The original signals from the sensors are collected by a Keithley data acquisition board and processed by fast Fourier transform (FFT). The amplitude and frequency of the magnetic flux density are extracted successfully. Based on the measured magnetic field distribution, the maximum of the interface displacement is reconstructed by an evolutionary strategy, which is in good agreement with the optical measurement. This MFT system can be applied to study the interface movements in aluminium reduction cells, in iron/steel making, in glass melts, and in other electromagnetic processing of materials.     

Two cases of depressive disorder after pacemaker implantation

We report 2 patients who showed psychological symptoms after pacemaker implantation. Pacemaker syndrome was excluded, and a diagnosis of depressive disorder not otherwise specified was made in both patients. Patient 1 complained of discomfort early after pacemaker implantation but became unaware of the pacemaker after 1 year. However, after 3 years, lack of activity, general fatigue, and unaccountable sensations developed. These symptoms improved with symbiosis with the pacemaker. Patient 2 developed many complications after pacemaker implantation. Therefore, he was markedly aware of the pacemaker as not-self and wanted to remove it. One month after implantation, unaccountable sensations and irritations began to occur. He did not return to work, and the symptoms improved with progression of "mourning for the loss of the perfection of the own body". In both patients, their symptoms improved after "acceptance that their own body depended on the pacemaker" and "symbiosis with the pacemaker as not-self", not complete integration of the pacemaker. Therefore, the psychological process after pacemaker implantation consisted of the establishment of "mourning for the loss of the perfection of the own body" and "symbiosis with not-self". In these patients, this process was impaired, causing depressive symptoms. This process resembled the integration process in patients undergoing dialysis or renal transplantation. As, compared with renal transplantation, it is more difficult to integrate the pacemaker to the own body, so, it seems better to aim for "symbiosis with the pacemaker" to promote the adjustment process. To promote the adjustment process and decrease depression, support after understanding of this psychological process is needed.     

Effect of N-acetylcysteine on human diaphragm strength and fatigability

Free radical injury is believed to be important in diaphragm dysfunction. N-Acetylcysteine (NAC) is a potent free radical scavenger shown in animal models to attenuate diaphragm fatigue; however, its effects on human diaphragm function are unknown. We assessed diaphragm function by electrophrenic twitch stimulation (PdiT) and twitch occlusion (to yield Pdimax) in four healthy subjects 35 +/- 3 yr of age (mean +/- SD). We intravenously administered NAC (150 mg/kg in 250 ml D5W) or placebo (CON) (250 ml D5W) in a randomized manner after subjects were premedicated with antihistamines. There were no significant side effects with the infusion. After infusion, we measured baseline Pdimax and PdiT at FRC. Diaphragm fatigue was then induced by subjects breathing through an inspiratory resistive load. Pdimax and PdiT were then measured at 15 to 30 min and 1, 2, 3, 4, and 20-25 h after fatigue. Times to fatigue were 13 +/- 4 min (CON) and 21 +/- 6 min (NAC) (p = 0.04). At 15 min after fatigue, PdiT was reduced to 40% (CON) compared with 30% (NAC) initial PdiT value (p = 0.05). Other twitch characteristics (maximal rate of relaxation and maximal contraction rate) were reduced to a greater degree after placebo compared with NAC. There were no significant differences in the rate of recovery between CON and NAC. Pdimax at 30 min after fatigue was significantly greater with NAC; however, at 1 h after fatigue, Pdimax for CON and NAC were not different, suggesting similar rates of recovery in high-frequency fatigue. These data suggest that NAC may attenuate low-frequency human diaphragm fatigue.     

Putative projection of phrenic afferents to the limbic cortex in humans studied with cerebral-evoked potentials

Respiratory sensations may rely in part on cortical integration of respiratory afferent information. In an attempt to study such projections, we recorded evoked potentials at scalp and cervical sites in 10 normal volunteers undergoing transcutaneous phrenic stimulation (0.1-ms square pulses, intensity liminal for diaphragmatic activation, series of 600 shocks at 2 Hz). A negative cerebral component of peak latency (12.79 +/- 0.54 ms; N13) was constant, and a negative spinal component (7.09 +/- 1.04 ms; N7) could also be recorded, all results being reproducible over time. Monitoring of cardiac frequency, skin anesthesia, and stimulation adjacent to the phrenic nerve made the phrenic origin of N7 and N13 the foremost hypothesis. Increasing stimulation frequency and comparison with median nerve stimulation provided arguments for the neural nature of the signals and their cerebral origin. Recordings from intracerebral electrodes in a patient showed a polarity reversal of the evoked potentials at the level of the cingulate gyrus. In conclusion, phrenic stimulation could allow one to study projections of phrenic afferents to the central nervous system in humans. Their exact site and physiological meaning remain to be clarified.     

Effects of intraphrenic injection of potassium on diaphragm activation

The purpose of the present study was to determine whether potassium, injected into the arterial supply of the diaphragm, would reflexly alter efferent diaphragmatic motor outflow and systemic arterial pressure. Studies were performed using in situ canine diaphragm muscle strips in which the inferior phrenic artery and vein were cannulated and all other sources of strip blood flow were ligated. Injection of potassium (0.1 meq) into the inferior phrenic artery elicited a small transient (1-2 breaths) decrease in the peak strip tension developed during spontaneous muscle contractions, in peak integrated strip electromyographic (EMG) activity, and in the peak integrated EMG activity of the contralateral hemidiaphragm. This was followed by a more pronounced and more sustained increase in each of these parameters as well as an increase in systemic arterial pressure. This latter excitatory response was qualitatively similar to that induced by the injection of capsaicin (5 and 25 micrograms) into the phrenic artery. Section of the left phrenic nerve abolished the effects of intra-arterial potassium and capsaicin on systemic arterial pressure and right hemidiaphragm EMG activity. These data support the existence of a potent excitatory phrenic-to-phrenic reflex that can be activated by potassium injection into the diaphragm. Activation of this pathway increases diaphragm motor activation and augments systemic arterial pressure.     

Influence of acute lung volume change on contractile properties of human diaphragm

The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity. The reduction in T2 Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% of vital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responses elicited by low-frequency stimulations; this effect is distinct from and additional to the known length-tension relationship.