Biomedical subjects

J Road

Publications and source records attributed to J Road.

At least 19 recordsLinked to original sources

PubMed2005

A direct nitric oxide gas delivery system for bacterial and mammalian cell cultures.

Nitric oxide (NO) is the smallest known gaseous signaling molecule released by mammalian and plant cells. To investigate the pathophysiologic role of exogenous NO gas (gNO) in bacterial and mammalian cell cultures, a validated in vitro delivery method is required. The system should be able to deliver gNO directly to bacterial and/or cell cultures in a continuous, predictable, and reproducible manner over a long period of time (days). To accomplish this, a gas delivery system was designed to provide optimal growth conditions for bacteria and/or mammalian cells. Parameters for cell exposure, such as concentration of gNO, nitrogen dioxide (NO(2)), oxygen (O(2)), temperature, and relative humidity (RH) were continuously monitored and evaluated. Uptake of gNO into various media was monitored by measuring the nitrite concentration using the Griess reagent technique. A selection of standard growth media [saline, tryptic soy broth (TSB), Middlebrook 7H9 (MB 7H9), and Dulbecco's modified Eagle's medium (DMEM)] exposed to various concentrations of gNO revealed a steady and consistent transfer of gNO into the aqueous phase over a 48-h period. Validation of optimal growth conditions within the device, as compared to a conventional incubator, were accomplished by growing and observing viability of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and human fibroblast cultures in the absence of gNO. These results indicate that an optimal growth environment for the above tested cells was accomplished inside the proposed delivery system. Dose-dependent toxicological data revealed a significant bacteriostatic effect on P. aeruginosa and S. aureus with continuous exposure to 80 ppm gNO. No toxic effects were observed on dermal fibroblast proliferation at concentrations up to 400 ppm gNO for 48 h. In conclusion, the designed gNO exposure system is capable of supporting cellular viability for a representative range of prokaryote and eukaryotic cells. The exposure system is also capable of obtaining toxicological data. Therefore, the proposed device can be utilized to continuously expose cells to various levels of gNO for up to 72 h to study the in vitro effects of gNO therapy.

Anti-Bacterial Agents↗

PubMed2003

Canine trachealis muscle shortening and cartilage mechanics.

Canine trachealis muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, trachealis muscle will shorten by only 30-40% when stimulated in vivo. To examine the possibility that an elastic load applied by the tracheal cartilage contributes to the in vivo limitation of shortening, single pairs of sonomicrometry crystals were inserted into the trachealis muscle at the level of the fifth cartilage ring in five dogs. The segment containing the crystals was then excised and mounted on a tension-testing apparatus. Points on the active length-tension curve and the passive length-tension relation of the cartilage only were determined. The preload applied to the muscle before contraction varied from 10 to 40 g (mean 21 +/- 4 g). The afterload applied by the cartilage during trachealis contraction ranged from 13 to 56 g (30 +/- 6 g). The calculated elastic afterloads were substantial and appeared to be sufficient to explain the degree of shortening observed in four of the seven rings; in the remaining three rings, the limitation of shortening was greater than would be expected from the elastic load provided by the cartilage. Additional sources of loading and/or additional mechanisms may contribute to limited in situ shortening. In summary, tracheal cartilage applies a preload and an elastic afterload to the trachealis that are substantial and contribute to the limitation of trachealis muscle shortening in vivo.

Animals↗

PubMed2001

Electromyography of respiratory muscles in amyotrophic lateral sclerosis.

We reviewed the records of 52 amyotrophic lateral sclerosis (ALS) patients examined between 1995 and 2000 who had needle electromyography (EMG) of their respiratory muscles, including the diaphragm, at or near the time of their diagnosis. With respiratory function testing, patients with abnormal diaphragmatic EMG at diagnosis (Group 1, n=23) had significantly lower forced vital capacity (FVC), lower daytime arterial PO(2) and higher PCO(2) measurements (p<0.05) than patients with normal diaphragmatic EMG (Group 2, n=29). Twenty-eight percent of the patients without symptoms or signs of respiratory insufficiency at the time they were examined had an abnormal diaphragm EMG. Mean survival of Groups 1 and 2 were similar. However, sub-analysis of patients within each group, comparing those treated with non-invasive positive pressure ventilation (NIPPV) with those not treated, showed that treated patients in Group 1 (abnormal diaphragm EMG) survived significantly longer (p<0.05) than untreated patients. They also started NIPPV earlier than treated patients in Group 2. We conclude that respiratory muscle EMG was simply and safely performed on ALS patients at or around the time of diagnosis. The procedure can detect sub-clinical respiratory muscle dysfunction. The technique used for EMG of the respiratory muscles, its pitfalls and contraindications are also reviewed.

Aged↗

PubMed2001

Myositis associated graft-versus-host-disease presenting as respiratory muscle weakness.

Myositis associated with graft-versus-host-disease (GVHD) typically presents with proximal muscle weakness, myalgias, and a raised creatinine phosphokinase (CPK) level. We report a case of a 51 year old man who developed respiratory muscle weakness five years after an allogeneic bone marrow transplant for multiple myeloma. His symptoms included tachypnoea, abdominal paradox, and orthopnoea. Pulmonary function tests revealed diminished vital capacity and maximal inspiratory and expiratory pressures. Serum CPK levels were raised and a peripheral muscle biopsy specimen was consistent with GVHD. He improved with immunosuppressive therapy.

Bone Marrow Transplantation↗

PubMed1999

Exhaled nitric oxide during exercise.

Endogenously produced nitric oxide (NO) is detectable in the exhaled air of resting humans, and the amount of exhaled NO increases during exercise. It is believed that NO is likely to have an important role in the normal physiological response to exercise. Despite accumulating evidence of exhaled NO during exercise, the effects and relevance of NO to exercise are not yet completely understood. Scientific debate surrounds the site of NO production and the stimuli for production. Resolution of these controversial issues will explain the significance of exhaled NO during exercise.

Animals↗

PubMed1997

Reversible paralysis with status asthmaticus, steroids, and pancuronium: clinical electrophysiological correlates.

Prolonged neuromuscular weakness has been identified after neuromuscular blockade in intensive care unit patients on mechanical ventilation. Previously reported electromyographic studies in these patients documented both neurogenic features and features consistent with a myopathy. We recorded sequential electrophysiological parameters during recovery from neuromuscular blockade in 5 patients with clinical weakness. An evolving pattern was identified. The early features were in keeping with previous reports of neurogenic changes, and this evolved into features consistent with a primary myopathy. Several potential underlying mechanisms are discussed.

Adult↗

PubMed1996

Effect of maximum ventilation on abdominal muscle relaxation rate.

BACKGROUND: When the demand placed on the respiratory system is increased, the abdominal muscles become vigorously active to achieve expiration and facilitate subsequent inspiration. Abdominal muscle function could limit ventilatory capacity and a method to detect abdominal muscle fatigue would be of value. The maximum relaxation rate (MRR) of skeletal muscle has been used as an early index of the onset of the fatiguing process and precedes failure of force generation. The aim of this study was to measure MRR of abdominal muscles and to investigate whether it slows after maximum isocapnic ventilation (MIV). METHODS: Five normal subjects were studied. Each performed short sharp expiratory efforts against a 3 mm orifice before and immediately after a two minute MIV. Gastric pressure (PGA) was recorded and MRR (% pressure fall/10 ms) for each PGA trace was determined. RESULTS: Before MIV the mean (SD) maximum PGA MRR for the five subjects was 7.1 (0.8)% peak pressure fall/10 ms. Following MIV mean PGA MRR was decreased by 30% (range 25-35%), returning to control values within 5-10 minutes. CONCLUSIONS: The MRR of the abdominal muscles, measured from PGA, is numerically similar to that described for the diaphragm and other skeletal muscles. After two minutes of maximal isocapnic ventilation abdominal muscle MRR slows, indicating that these muscles are sufficiently heavily loaded to initiate the fatiguing process.

Abdominal Muscles↗

PubMed1996

Diaphragm fatigue following maximal ventilation in man.

When highly motivated normal subjects perform maximal isocapnic ventilation, a substantial fall in ventilation is observed during the first minute associated with slowing of the maximum relaxation rate (MRR) of the inspiratory muscles. This suggests that these muscles are excessively loaded, raising the possibility that overt contractile failure of the diaphragm contributes to the fall in ventilation. We therefore investigated the effect of maximal isocapnic ventilation (MIV) on twitch transdiaphragmatic pressure (Pdi,Tw) elicited by cervical magnetic stimulation. We measured Pdi,Tw before and after 2 min MIV in nine normal subjects. Initial mean (SD) ventilation for the nine subjects was 196 (15) L.min-1 falling by 35% at 1 min. Pdi,Tw fell following MIV, at 10 min was reduced by 24%, and remained substantially reduced 90 min after MIV. No change in Pdi,Tw was observed during control studies in which subjects were studied with the same protocol but omitting MIV. We conclude that diaphragmatic contractility is reduced after 2 min maximal isocapnic ventilation and diaphragmatic fatigue may be a limiting factor in maximal ventilation in man.

Adult↗

PubMed1995

Phrenic motoneuron firing rates during brief inspiratory resistive loads.

The neural activation of the diaphragm during quiet and vigorously stimulated breathing has been hypothesized to be submaximal. In this study, we measured phrenic motoneuron firing rates during brief progressively increasing inspiratory resistive loads in anesthetized rabbits. We recorded activity in 68 phrenic motoneurons in 17 rabbits. We found that 40 of these axons were active during quiet breathing. Twenty-seven axons were silent during quiet breathing but began to fire as inspiratory loading progressed. The level of drive reflected by transdiaphragmatic pressure where silent phrenic motoneurons were recruited ranged from 5 to 45 cmH2O. Silent motoneurons showed significantly higher average rates of firing and significantly greater increases in firing rate as loading progressed (P < 0.01). The firing rate of both active and silent axons tended to plateau as rates approached 70-80 Hz. All motoneurons except for one, which may have been an afferent, were activated by inspiratory resistive loading. Inspiratory resistive loading activated phrenic motoneurons at high rates, and our results did not support the presence of significant numbers of unrecruited motoneurons.

Animals↗

PubMed1995

The effect of lung volume on transdiaphragmatic pressure.

Diaphragm strength can be assessed by measurement of transdiaphragmatic pressure (Pdi) in response to stimulation of the phrenic nerves. The length-tension relationship of the diaphragm can be studied by measuring twitch Pdi over the range of lung volume. Previous studies of the relationship between lung volume and diaphragm strength have used the technique of electrical stimulation of the phrenic nerves. In these studies, the phenomenon of twitch potentiation has not been taken into account. It has previously been shown that prior contraction of the diaphragm can greatly enhance the twitch response, thus affecting the measurements. The aim of this study was to investigate the relationship between unpotentiated twitch Pdi and lung volume for volumes ranging from residual volume (RV) to total lung capacity (TLC) in normal subjects. Great care was taken to avoid muscle potentiation. For this purpose, we stimulated the phrenic nerves with a magnetic stimulator. In addition, we used positive pressure to inflate the lungs to high lung volumes. The impact of twitch potentiation on the length-tension relationship was investigated by subjects making maximum inspiratory efforts prior to phrenic nerve stimulation. The unpotentiated twitch Pdi decreased in a linear fashion with increasing lung volume over the full range of vital capacity by 0.54 kPa.L-1. Potentiation increased twitch Pdi by 40% at FRC and the effect was similar, in absolute terms, at all lung volumes. In relative terms, the effect of potentiation became greater as lung volume increased, and more than doubled twitch Pdi at TLC. With increasing lung volume, there is a linear fall in unpotentiated twitch Pdi with a slope that is less steep, over the same range of absolute lung volume, than previously reported. When assessing diaphragm strength by the twitch technique, it is essential to control for lung volume and equally important to control for twitch potentiation.

Adult↗

PubMed1994

Inspiratory muscle relaxation rate assessed from sniff nasal pressure.

BACKGROUND: Slowing of the maximum relaxation rate (MRR) of inspiratory muscles measured from oesophageal pressure (POES) during sniffs has been used as an index of the onset and recovery of respiratory muscle fatigue. The purpose of this study was to measure MRR at the nose (PNASAL MRR), to investigate its relationship with POES MRR, and to establish whether PNASAL MRR slows with respiratory loading. METHODS: Five normal subjects were studied. Each performed sniffs before and after two minutes of maximal isocapnic ventilation (MIV). In a separate session the subjects performed submaximal sniffs. POES and PNASAL were recorded during sniffs and the MRR (% pressure fall/10 ms) for each sniff was determined. RESULTS: Before MIV mean POES MRR was 8.9 and PNASAL MRR was 9.3. The mean (SD) difference between PNASAL MRR and POES MRR during a maximal sniff was 0.48 (0.34) (n = 64) and during submaximal sniffs was 0.28 (0.46) (n = 526). The subjects showed a mean decrease in sniff POES MRR of 27.4% (range 22.5-36%) after MIV and a similar reduction in sniff PNASAL MRR of 28.5% (range 24.1-41.3%). Both returned to control values within 5-10 minutes. CONCLUSIONS: PNASAL MRR reflects POES MRR over a wide range of sniff pressures, PNASAL MRR of maximal sniffs reflects POES MRR in normal subjects at rest and following MIV, so measurement of PNASAL MRR may be a useful non-invasive method for measuring inspiratory muscle MRR, thereby providing an index of respiratory muscle fatigue.

Air Pressure↗

PubMed1994

Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects.

BACKGROUND: Skeletal muscle twitch responses may be transiently increased by previous contractions, a phenomenon termed twitch potentiation. The aim of this study was to examine the extent and time course of diaphragmatic twitch potentiation and its relationship to both the magnitude and duration of the preceding voluntary diaphragmatic contraction. METHODS: Twitch transdiaphragmatic pressure (PDI) was measured in six normal subjects, before and after voluntary diaphragm contractions of 100%, 75%, 50%, and 25% of maximum PDI (PDImax) sustained for five and 10 seconds. RESULTS: Twitch PDI was significantly increased after 100%, 75%, and 50% contractions. Following maximal contractions sustained for 10 seconds the mean increase in twitch PDI was 52%. Following 50% contractions sustained for five seconds the mean increase in twitch height was 28%. In all runs twitch PDI returned to rested levels within 20 minutes. CONCLUSIONS: Twitch potentiation can be substantial, even following submaximal contractions, and must be taken into account when twitch pressure is used to assess diaphragm contractility.

Adult↗

PubMed1994

Tumor necrosis factor alpha decreases in vivo diaphragm contractility in dogs.

In this study, we hypothesized that tumor necrosis factor alpha (TNF alpha) is an important mediator of sepsis-related impairment in diaphragm contractility (1-2). In 12 anesthetized, ventilated dogs, bipolar stimulating electrodes were placed on the phrenic nerves and diaphragm electromyographic activity (EMG) and shortening were recorded with needle electrodes and piezoelectric crystals, respectively. Transdiaphragmatic pressure (Pdi) was also recorded using esophageal (Pes) and abdominal balloon catheters (Pdi = Pab-Pes). Dogs were randomized to receive saline injection (n = 6), or TNF alpha 60 micrograms/kg (n = 6). All parameters were recorded hourly for 6 h. Mean arterial blood pressure decreased 1 h after infusion in TNF alpha animals (p < 0.05) with no significant change thereafter. Cardiac output increased early after TNF alpha infusion (p < 0.05) and remained at greater than baseline values at study termination. Diaphragm pressure generation and costal shortening decreased progressively from 3 to 6 h post TNF alpha infusion (p < 0.05) with no significant change in control animals. Compound diaphragm action potential in response to supramaximal phrenic stimulation decreased in TNF alpha animals (p < 0.01) with no significant change in control animals 3 and 6 h postinfusion. We conclude that TNF alpha infusion was associated with significant declines in isotonic and quasi-isometric diaphragm contraction and that this could be explained, at least in part, by impaired neuromuscular transmission.

Action Potentials↗

PubMed1992

In vivo and in vitro correlation of trachealis muscle contraction in dogs.

Maximal trachealis muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the muscle was evaluated in vitro. In vivo trachealis muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the trachealis muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.

Animals↗

PubMed1991

Recovery of costal and crural diaphragmatic contractility from partial paralysis.

Since the two muscles (costal and crural) that constitute the diaphragm are separate and histologically different, their individual recovery pattern from neuromuscular blockade also may be different. Therefore, we studied the recovery of force and shortening in the in vivo diaphragm from atracurium-induced neuromuscular blockade in seven pentobarbital anesthetized dogs to assess segmental differences. Transdiaphragmatic pressure (Pdi), shortening of costal and crural segments, integrated electromyogram (EMG), and tidal volume (VT) were measured during spontaneous breathing. After atracurium had reduced VT to 30% of control, breathing parameters were followed until recovered to 90% of control values. In addition, force-frequency curves generated by supramaximal tetanic stimuli of the phrenic nerve were measured. Recovery times for tidal Pdi, tidal EMG, tidal shortening, low-frequency shortening, and twitch Pdi were twice as fast as for VT (40 +/- 4 min), reflecting a slower rate of recovery of accessory inspiratory muscles. High-frequency recovery was typically slower than that of VT. During tidal breathing and tetanic stimulation, costal and crural shortening recovered simultaneously. On the other hand, comparison between costal and crural by analysis of pressure-shortening relationships showed a segmental difference (crural shortened 30% more than costal at the same Pdi), which implied reduced afterload on the crural segment. However, since shortening and pressure were linearly related during paralysis and recovery, measurements of Pdi alone can accurately reflect changes in contractile mass when heterogeneity and afterload are controlled.

Animals↗

PubMed1990

Tracheal smooth muscle mechanics in vivo.

We applied the technique of sonomicrometry to directly measure length changes of the trachealis muscle in vivo. Pairs of small 1-mm piezoelectric transducers were placed in parallel with the muscle fibers in the posterior tracheal wall in seven anesthetized dogs. Length changes were recorded during mechanical ventilation and during complete pressure-volume curves of the lung. The trachealis muscle showed spontaneous fluctuations in base-line length that disappeared after vagotomy. Before vagotomy passive pressure-length curves showed marked hysteresis and length changed by 18.5 +/- 13.2% (SD) resting length at functional residual capacity (LFRC) from FRC to total lung capacity (TLC) and by 28.2 +/- 16.2% LFRC from FRC to residual volume (RV). After vagotomy hysteresis decreased considerably and length now changed by 10.4 +/- 3.7% LFRC from FRC to TLC and by 32.5 +/- 14.6% LFRC from FRC to RV. Bilateral supramaximal vagal stimulation produced a mean maximal active shortening of 28.8 +/- 14.2% resting length at any lung volume (LR) and shortening decreased at lengths above FRC. The mean maximal velocity of shortening was 4.2 +/- 3.9% LR.S-1. We conclude that sonomicrometry may be used to record smooth muscle length in vivo. Vagal tone strongly influences passive length change. In vivo active shortening and velocity of shortening are less than in vitro, implying that there are significant loads impeding shortening in vivo.

Animals↗

PubMed1989

Chronic eosinophilic pneumonia: CT findings in six cases.

We reviewed the chest radiographs and CT scans in six patients with proved chronic eosinophilic pneumonia. In all patients, the chest radiographs showed patchy air-space consolidation, and in five of six cases, the consolidation was most marked in the middle and upper lung zones. In only one patient was the classic pattern of air-space consolidation that is confined to the outer third of the lungs readily apparent. In three patients, the consolidation appeared to be diffuse, although a slight peripheral predominance was present. In two patients, a peripheral predominance was difficult to appreciate, even in retrospect. The CT scans in all cases showed peripheral air-space consolidation. In addition, mediastinal adenopathy was identified on CT scans in three cases. This has not been described before in association with chronic eosinophilic pneumonia. A follow-up CT scan in one patient showed resolution of the adenopathy and marked improvement in the peripheral air-space disease within 2 weeks. We conclude that patients with chronic eosinophilic pneumonia show predominantly peripheral air-space consolidation on CT scans, even when this distribution is not readily apparent on the radiograph. CT may be helpful in the diagnosis when the clinical findings are suggestive, but the radiographic pattern is nonspecific.

Adult↗

PubMed1987

In vivo contractile properties of fatigued diaphragm.

The effects of fatigue on diaphragmatic contractility in vivo are unknown. In this study we used sonomicrometry to examine the velocity of shortening and lengthening and the amount of shortening in the fresh and fatigued canine hemidiaphragm (8 dogs) including the force generated. Fatigue was produced by epiphrenic stimulation of the left phrenic nerve; the right hemidiaphragm acted as the control. We found that 1) hemidiaphragmatic fatigue caused an increase in frequency with reduced tidal volume; 2) fatigue resulted in a near complete cessation of tidal shortening during spontaneous breathing; 3) there was an initial decrease in central activation (electromyogram) to the fatigued hemidiaphragm, an indication of central fatigue; 4) force-frequency curves showed a considerable and prolonged loss of the amount of shortening, velocity, and force generated by the fatigued hemidiaphragm during supramaximal stimulation, an indication of peripheral fatigue; and 5) during spontaneous breathing in the fatigued hemidiaphragm, tidal shortening remained reduced for up to 3 h, whereas in the right right hemidiaphragm tidal shortening and electromyographic activity did not change. We conclude that fatigue of a hemidiaphragm alters the spontaneous breathing pattern and produces profound modifications in its contractile properties without altering contralateral hemidiaphragmatic performance.

Animals↗