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Biomedical subjects

J D Road

Publications and source records attributed to J D Road.

At least 19 recordsLinked to original sources
PubMed2006

Increased injury and intramuscular collagen of the diaphragm in COPD: autopsy observations.

Evidence for diaphragm injury in people with chronic obstructive pulmonary disease (COPD) has been reported, although the extent of injury and collagen accumulation post mortem have not previously been examined. In addition, it is not known whether the amount of injury and collagen are different in key regions of the diaphragm. The cross-sectional area of collagen and the percentage of abnormal myofibres in the post mortem diaphragm and psoas major were determined by computer-assisted image analysis of stained cross-sections of the diaphragm for collagen with picrosirius red and with haematoxylin and eosin for morphology. In the midcostal diaphragm of six subjects with COPD and six subjects with no significant respiratory disease, the COPD diaphragm displayed a greater cross-sectional area of collagen and percentage of abnormal myofibres (collagen: 24.2+/-1.0 versus 18.6+/-1.1%; injury: 28.4+/-7.2 versus 12.0+/-1.3%). In 18 patients with various respiratory conditions, the midcostal diaphragm displayed more collagen and abnormal myofibres than the crural diaphragm, while both costal and crural diaphragms displaying more collagen and abnormal myofibres than psoas major. This study reveals extensive injury and collagen accumulation in the chronic obstructive pulmonary diseased diaphragm, and reveals a regional pattern of injury and intramuscular collagen which may correspond to variations in diaphragm loading.

Analysis of Variance↗
PubMed2005

Granulocytosis and increased adhesion molecules after resistive loading of the diaphragm.

Upregulation of endothelial cell adhesion molecules, followed by an influx of granulocytes and macrophages, can contribute to exertion-induced skeletal muscle injury. The purpose of this study was to quantify circulating leukocyte subsets, diaphragm injury and infiltrating leukocyte subsets, and surface expression of vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 in the diaphragm after inspiratory resistive loading (IRL). Eight New Zealand white rabbits underwent 1.5 h of IRL and seven control rabbits underwent a sham procedure. Blood samples, taken at baseline and 2, 6, 12, 24, 48 and 72 h after the onset of IRL or sham, showed that band cell counts had increased at 6 h post-IRL. Point counting of haematoxylin and eosin-stained cross-sections, sampled at 72 h post-IRL, showed greater injury in diaphragms from IRL rabbits compared with controls. Immunohistochemical processing showed increased expression of ICAM-1 and VCAM-1, and higher granulocyte and macrophage counts in IRL diaphragms than control diaphragms. Macrophages were the predominant inflammatory cells. Increased intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, and infiltration of granulocytes and macrophages may contribute to inspiratory resistive loading-induced diaphragm injury.

Airway Resistance↗
PubMed2001

Free radical scavengers and diaphragm injury following inspiratory resistive loading.

Three groups of NZW rabbits were studied to examine the role of free radical scavengers in preventing diaphragm injury produced by inspiratory resistive load (IRL): control, IRL, and scavenger groups. An IRL (Pao: 45-55 cm H2O) was applied to the IRL and the scavenger groups on Day 1. Free radical scavengers (polyethylene glycol superoxide dismutase, N-acetylcysteine, and mannitol) were given (intravenously) to the scavenger group both before and after the IRL. All rabbits were killed on Day 3 to collect diaphragms. Point counting H&E-stained diaphragm x-sections indicated that abnormal diaphragm muscle in the IRL group was significantly greater than control (p < 0.01). However, it was significantly lower in the scavenger group than the IRL group (p < 0.05) and it did not differ from control. In vitro diaphragm physiological studies found that the twitch tension (p < 0.05) and maximal tension (p < 0.01) in the IRL group were significantly lower than control. The maximal tensions (p < 0.05) in the scavenger group were lower than control. After the fatigue protocol, diaphragmatic contractility in the scavenger group was similar to control and was better maintained compared with the IRL group. We conclude that free radical scavengers can prevent the development of diaphragm injury as evidenced by histology but the protection of diaphragm function is limited.

Animals↗
PubMed2001

Diaphragm injury in individuals with airflow obstruction.

The purpose of this study was to describe the nature of diaphragm injury, to quantify the injury and number of macrophages at the light microscopic level, and to determine their association with airflow obstruction in humans. Partial-thickness diaphragm biopsies were obtained from 21 subjects going for thoracotomy surgery (FEV(1): 74 +/- 34% predicted; range: 16 to 122% predicted). Cross sections cut from frozen diaphragm were processed with H&E or processed for immunohistochemistry using the monoclonal antibody Ber-MAC3 (DAKO Corp., Carpinteria, CA) to label macrophages. Area fractions (A(A)) or the proportions of the cross- sectional area were determined by point counting all viable fields of H&E-stained diaphragm cross sections. A(A) were 66.2 +/- 9.0% for normal muscle, 17.6 +/- 7.2% for abnormal muscle, and 16.3 +/- 4.2% for connective tissue. Percent predicted FEV(1) was inversely related to the A(A) of abnormal muscle (r = -0.53, p < 0.01) and directly related to the A(A) of normal muscle (r = 0.37, p < 0.05). The number of macrophages was not related to % predicted FEV(1) (mean +/- SD: 0.41 +/- 0.18/fiber; 52 +/- 19/mm(2)). We conclude that increasing severity of airflow obstruction is associated with an increased A(A) of abnormal diaphragm and a decreased A(A) of normal diaphragm.

Adult↗
PubMed1998

High-frequency oscillation and centroid frequency of diaphragm EMG during inspiratory loading.

Power spectra were derived from the diaphragm electromyogram (EMG) in anesthetized rabbits subjected to inspiratory resistive loading (IRL) with airway pressure swings of 40-60 cm H2O for 20 min to 2 h. Shifts in the centroid frequencies of the power spectra were found to be associated with the appearance of power spectral peaks in the range of 105-140 Hz, termed high-frequency oscillation, or HFO. Such peaks have been described before in phrenic nerve activity and in the diaphragm EMG. However, these peaks have not previously been connected with the shifts in centroid frequency seen during loaded breathing. Although such changes in frequency content have been taken to indicate fatigue in the diaphragm, we find that HFO can also cause a shift in centroid frequency during loaded breathing, an effect whose relation to fatigue has yet to be established.

Air Pressure↗
PubMed1998

Determinants of diaphragmatic injury.

Limb muscles can be injured during and after vigourous contractions. However, this injury is most evident under specific conditions. The strength and type of muscle contraction as well as the contractile status of the muscle are important determinants of injury. The initiating event leading to muscle injury is not clearly understood but there are several leading theories. The respiratory muscles are of obvious importance to survival, and fatigue or injury to them has been hypothesized to be prevented by various mechanisms. One such mechanism is reduced activation by the central nervous system. In this review information on the neural activation of the breathing muscles during inspiratory loading is discussed and reveals that neural activation to the diaphragm, the main inspiratory muscle, is high. Previous studies investigating the presence of muscle fatigue immediately after such inspiratory loading have shown little evidence of it. However, based on information from limb muscles, delayed or secondary muscle injury might occur and could produce deleterious effects on respiratory muscle function. Recent evidence shows that chronic low intensity inspiratory loading can produce diaphragmatic injury (Reid et al.) and secondary or delayed muscle injury can occur three days after an acute period of high intensity inspiratory loading. The results reviewed in this article suggest that the respiratory muscles, specifically the diaphragm, are not spared from injury or the results of muscle injury. Diaphragmatic function during the period of secondary muscle injury is markedly impaired and thus respiratory muscle injury is a phenomenon that warrants further investigation.

Airway Resistance↗
PubMed1998

Load dependence of secondary diaphragm inflammation and injury after acute inspiratory loading.

Chronic or prolonged low-intensity loading of the inspiratory muscles has recently been shown to produce diaphragm injury. The present study was designed to examine whether an acute episode of inspiratory resistive loading (IRL) could produce secondary diaphragm inflammation and injury. On Day 1, three groups of anesthetized and intubated New Zealand White rabbits were subjected to moderate IRL (Pao of approximately 30 cm H2O), high IRL (Pao of approximately 45 cm H2O), or no load for 1.5 h. On Day 3, costal and crural diaphragms, parasternals, and gastrocnemius muscles were taken to assess injury by point counting. Normal muscle, abnormal and inflamed muscle, and connective tissue on hematoxylin and eosin-stained cross-sections were expressed as percentage of the total points for that cross-section. For the costal diaphragm, both the abnormal muscle (7.3 +/- 0.6% versus 1.1 +/- 0.2%; p < 0.001) and connective tissue (8.0 +/- 0.6% versus 5.7 +/- 0.2%; p < 0.01) in the high IRL group were higher than control, whereas in the moderate IRL group they were not significantly different from control. Total calpain-like activity was increased in the moderate IRL group but not in the high IRL group. Injury was observed in the parasternal muscles but to a lesser extent. No injury was observed in the gastrocnemius muscle. We conclude that secondary diaphragm injury occurs after acute IRL but only when the IRL exceeds the fatigue threshold.

Acute Disease↗
PubMed1998

Delayed diaphragm injury and diaphragm force production.

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.

Adipose Tissue↗
PubMed1997

Phrenic motoneuron firing rates before, during, and after prolonged inspiratory resistive loading.

Phrenic motoneuron firing rates during brief inspiratory resistive loading (IRL) are high, and nearly all the motoneurons are recruited. Diaphragmatic fatigue has been difficult to demonstrate during IRL. Furthermore, evidence from studies in limb muscles has shown variable motoneuron responses to prolonged high-intensity loads. We studied phrenic motoneuron firing rates before, during, and after prolonged IRL in anesthetized rabbits. Of 117 phrenic axons, only 2 axons were not recruited; 41 axons were silent during unloaded breathing but were recruited at higher loads. Silent axons showed a more rapid increase in firing rate as the load increased. Phrenic motoneuron firing rates increased throughout the period of loading, whereas airway pressure swings did not. After prolonged IRL, higher motoneuron firing rates were needed during brief loads to produce the same airway pressure. No evidence of a decline in motoneuron firing rates was seen at any point. We conclude that the respiratory muscles can be shown to demonstrate physiological responses consistent with fatigue during prolonged IRL, and activation rates are high and remain so throughout this prolonged loading.

Action Potentials↗
PubMed1996

Effect of the beta-agonist clenbuterol on dexamethasone-induced diaphragm dysfunction in rabbits.

The present study was designed to examine whether clenbuterol (CLEN) could reduce dexamethasone (DEX)-induced diaphragm dysfunction. We studied four groups of New Zealand white (NZW) rabbits, each receiving one of the following daily injections subcutaneously for 2 wk: saline (control), DEX 3 mg/kg, DEX 3 mg/kg + CLEN 2 mg/kg, and CLEN 2 mg/kg. Diaphragm fiber cross-sectional areas (CSA) were measured. Twitch transdiaphragmatic pressure (Pdi) and tetanic Pdi were measured during bilateral phrenic stimulation both before and after 60 min of inspiratory resistive loading (IRL). DEX produced a marked atrophy of type IIa and type IIb diaphragm fibers. This diaphragm atrophy was prevented by CLEN in the DEX plus CLEN group. CLEN alone increased CSAs of all three types of diaphragm fibers. Significant reductions in twitch Pdi and tetanic Pdi at all stimulation frequencies both before and after IRL were observed similarly in the DEX group as well as in the DEX plus CLEN group compared with the control animals. We conclude that DEX produces significant diaphragm atrophy and decreases diaphragmatic contractility. CLEN produces hypertrophy of the diaphragm and minimizes diaphragm atrophy induced by DEX, but it has no demonstrable protective effect on DEX-induced diaphragm dysfunction.

Adrenergic beta-Agonists↗
PubMed1995

Some effects of vagal blockade on abdominal muscle activation and shortening in awake dogs.

1. The mechanisms of abdominal muscle activation are thought to be different during expiratory threshold loading (ETL) compared with hypercapnia. Our objectives in the present study were to determine the effects of removing excitatory vagal feedback on abdominal muscle activation, shortening and pattern of recruitment during ETL and hypercapnia. Six tracheotomized dogs were chronically implanted with sonomicrometer transducers and fine wire EMG electrodes in each of the four abdominal muscles. Muscle length changes and EMG activity were studied in the awake dog during ETL (6 dogs) and CO2 rebreathing (3 dogs), before and after vagal blockade. 2. Following vagal blockade, the change in volume (increase in functional residual capacity, FRC) during ETL was greater and active phasic shortening of all the abdominal muscles was reduced, when shortening was compared with a similar change in lung volume. Similarly, at comparable minute ventilation, abdominal muscle active shortening was also reduced during hypercapnia. The internal muscle layer was recruited preferentially in both control and vagally blocked dogs during both ETL and hypercapnia. 3. The degree of recruitment of the abdominal muscles during ETL and hypercapnia in awake dogs is influenced by vagal feedback, but less so than in anaesthetized dogs. These results illustrate the importance of the vagi and abdominal muscle activation in load compensation. However, vagal reflexes are apparently not contributing to the preferential recruitment of the internal muscle layer. In awake dogs during vagal blockade abdominal muscle recruitment still occurs by extravagal mechanisms.

Abdominal Muscles↗
PubMed1995

The effect of anesthesia on abdominal muscle resting length and shortening in awake dogs.

The objectives of this study were to examine the effects of anesthesia and implantation of sonomicrometer transducers on tonic and phasic expiratory activity of the abdominal muscles. Eight tracheotomized dogs were chronically instrumented with sonomicrometer transducers placed in each of the four abdominal muscles. The dogs were studied in the lateral decubitus position immediately after transducer implantation, while under halothane anesthesia, and then in the awake dogs 2 to 3 days postimplantation, and repeatedly over a 2- to 8-week period. The resting length (LRL) of the rectus abdominis (RA) was reduced in the first awake study compared to during anesthesia, but there was no change in LRL of the other abdominal muscles. The abdominal muscles phasically, actively, shortened during expiration more in the awake state than in the anesthetized state. The internal abdominal muscle layer (transversus abdominis and internal oblique) shortened phasically more than the external layer (RA and external oblique). Neither the LRL nor the amount of phasic shortening of the abdominal muscles changed significantly over the period in which transducers were in situ (2-8 weeks). Muscle sections excised at the end of each study exhibited small capsules of fibrosis immediately surrounding the transducers with normal muscle tissue between pairs of transducers. In conclusion, both tonic and phasic respiratory activity of the abdominal muscles, reflected by changes in resting length and the amount of active shortening, respectively, were absent during halothane anaesthesia and chronic implantation of sonomicrometer transducers per se had no effect.

Abdominal Muscles↗
PubMed1995

Diaphragm and phrenic nerve activities during inspiratory loading in anesthetized rabbits.

To determine whether decreases in neural activation and/or neuromuscular transmission to the diaphragm contribute to ventilatory failure observed during inspiratory resistive loaded breathing, peak integrated activity of the intact phrenic nerve (ENGdi) and costal diaphragm (EMGdi), transdiaphragmatic pressure swings (Pdi) and evoked diaphragm compound action potentials (M-wave) were measured in anesthetized rabbits subjected to inspiratory resistive loads of varying intensities and duration breathing supplemental oxygen. Sustainable loads were studied for 4 h. Severe loads were applied in increments and studied for 50 min each. Loading resulted in parallel increases in ENGdi, EMGdi and Pdi that stabilized within 20 min. With severe loading, peak inspiratory pressure (Pao = -55 +/- 4 cm H2O) was maintained for 30 min after which there was a significant drop in inspiratory pressure (task failure). Despite hypoventilation and profound changes in blood gases, both activation (ENGdi) and neuromuscular transmission (ENGdi/EMGdi ratio or M-wave) were maintained throughout all loads even at task failure when a critical level of PaO2 (27 +/- 1 mm Hg) was reached. We conclude that neural activation and neuromuscular transmission to the diaphragm do not fail during inspiratory resistive breathing and discuss our findings in terms of current concepts of diaphragm fatigue and control of breathing in this model.

Anesthesia↗
PubMed1995

Stability of evoked parasternal intercostal muscle electromyogram at increased end-expiratory lung volume.

The diaphragmatic electromyogram has been measured as an index of the level of diaphragmatic activation. The diaphragmatic electromyogram, however, even when measured by intramuscular electrodes, can be artifactually altered by a change in lung volume (A. Brancatisano, S. M. Kelly, A. Tully, S. H. Loring, and L. A. Engel. J. Appl. Physiol. 66: 1699-1705, 1989) or by a change in body position. The parasternal intercostal muscle may be less subject to the mechanisms that are believed to produce this artifactual change. We asked whether the parasternal intercostal electromyographic activity could be reliable when lung volume changes. Six supine rabbits were anesthetized with ketamine and xylazine. Fine bipolar copper wires, with their tips exposed, were inserted into the left parasternal intercostal muscle in the third interspace. A stimulus that was three times maximal was applied to the corresponding intercostal nerve, and the resulting action potential (AP) was photographed. Parasternal intercostal muscle length was measured by sonomicrometry over the vital capacity range. There were small nonsignificant changes in the AP from functional residual capacity (FRC) to total lung capacity. From FRC to residual volume there was variation in the AP. The AP was also quite stable when regional conductivity was altered but showed variation when the parasternal intercostal muscle length change was accentuated by traction on the rib cage. We conclude that the parasternal intercostal electromyographic activity can be reliably used to measure inspiratory motoneuron output to it over the range of lung volumes from FRC to total lung capacity.

Animals↗
PubMed1995

Ventilatory muscle strength and endurance in myasthenia gravis.

Patients with generalized myasthenia gravis (MG) often have associated ventilatory muscle involvement. It is not known whether patients with isolated ocular muscle involvement have identifiable involvement of their ventilatory muscles. Most studies have assessed muscle involvement by measuring muscle strength; however, we hypothesized that measures of ventilatory muscle endurance may be more sensitive tests of ventilatory muscle involvement in myasthenia gravis. We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response. We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs.

Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor.

Animals↗
PubMed1994

Abdominal muscle activity during hypercapnia in awake dogs.

We previously found the internal abdominal muscle layer to be preferentially recruited during expiratory threshold loading in anesthetized and awake dogs. Expiratory threshold loading increases end-expiratory lung volume and hence can activate reflex pathways such as tonic vagal reflexes, which could influence abdominal muscle recruitment. Our objectives in the present study were to determine the effects of hypercapnia on abdominal muscle activation and the pattern of recruitment in awake dogs. Five tracheotomized dogs were chronically implanted with sonomicrometer transducers and fine-wire electromyogram (EMG) electrodes in each of the four abdominal muscles: transversus abdominis, internal oblique, external oblique, and rectus abdominis. Muscle length changes and EMG activity were studied in the awake dog at rest and during CO2 rebreathing. CO2 rebreathing produced a tripling of tidal volume and activation of the abdominal muscles. Despite the increase in tidal volume, there was no significant change in abdominal muscle end-inspiratory length. Both tonic and phasic expiratory shortening were greater in the internal muscle layer (transversus abdominis and internal oblique) than in the external muscle layer (external oblique and rectus abdominis). We conclude that the internal abdominal muscles are preferentially recruited by hypercapnia and vagal reflexes probably do not contribute to this differential recruitment but that segmental reflexes may be involved. The mechanical consequences of this recruitment are discussed.

Abdominal Muscles↗