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Biomedical subjects

R L Pardy

Publications and source records attributed to R L Pardy.

At least 37 records · Page 2Linked to original sources

Proportions and sizes of muscle fiber types in the hamster diaphragm.

This study demonstrated that there was interanimal and interregional variability of proportions and sizes of the muscle fiber types in the hamster diaphragm. Muscle fiber type proportions and sizes were determined for each side (right, left), surface (abdominal, thoracic), and region (sternal, anterior costal, posterior costal, crural) in six hamsters. There was marked regional and surface-to-surface variability and some interanimal variability in proportions and sizes of fiber type within the hamster diaphragm. The sternal and costal regions were relatively homogeneous. However, there were differences in both proportions and sizes of fiber types between the thoracic surface of the crural region and the abdominal surface of the crural region. These two surfaces of the crural region differed from the rest of the diaphragm. For muscle fiber type proportions, type 2a fibers demonstrated the most interanimal variability. Muscle fiber size varied little between animals.

Animals↗

Diaphragmatic weakness and paralysis.

Diaphragmatic weakness implies a decrease in the strength of the diaphragm. Diaphragmatic paralysis is an extreme form of diaphragmatic weakness. Diaphragmatic paralysis is an uncommon clinical problem while diaphragmatic weakness, although uncommon, is probably frequently unrecognized because appropriate tests to detect its presence are not performed. Weakness of the diaphragm can result from abnormalities at any site along its neuromuscular axis, although it most frequently arises from diseases in the phrenic nerves or from myopathies affecting the diaphragm itself. Presence of diaphragmatic weakness may be suspected from the complaint of dyspnea (particularly on exertion) or orthopnea; the presence of rapid, shallow breathing or, more importantly, paradoxical inward motion of the abdomen during inspiration on physical examination; a restrictive pattern on lung function testing; an elevated hemidiaphragm on chest radiograph; paradoxical upward movement of 1 hemidiaphragm during fluoroscopic imaging; or reductions in maximal static inspiratory pressure. The diagnosis of diaphragmatic weakness is confirmed, however, by a reduction in maximal static transdiaphragmatic pressure (Pdimax). The diagnosis of diaphragmatic paralysis is confirmed by the absence of a compound diaphragm action potential on phrenic nerve stimulation. There are many causes of diaphragmatic weakness and paralysis. In this review we outline an approach we have found useful in attempting to determine a specific cause. Most frequently the cause is either a phrenic neuropathy or diaphragmatic myopathy. Often the neuropathy or myopathy affects other nerves or muscles that can be more easily investigated to determine the specific pathologic basis, and, by association, it is presumed that the diaphragmatic weakness or paralysis is secondary to the same disease process.

Diaphragm↗

Diaphragmatic plate electrode stimulation of the hamster diaphragm.

We developed a new technique of diaphragmatic stimulation by apposing plate electrodes directly against the diaphragm (DPS) in adult Golden Syrian hamsters. The electrophysiological and the mechanical responses to DPS were compared with those with phrenic nerve stimulation. In four animals, evaluation of the electromyogram before and after curare demonstrated that plate electrode stimulation occurred via the phrenic nerve filaments. In four animals, similar transdiaphragmatic pressure was produced at maximal current with DPS and phrenic nerve stimulation. Using DPS increasing current beyond a certain level resulted in recruitment of muscles besides the diaphragm. In six animals, an external abdominal pressure of 15 cmH2O produced maximal transdiaphragmatic pressure, suggesting that the diaphragm was contracting near optimal position with this external abdominal pressure. In another four animals the twitch and pressure-frequency characteristics with the use of DPS were found to be reproducible over a 2-h period. We conclude that DPS is an effective method of diaphragmatic stimulation and should prove to be a valuable technique to study the diaphragm in long-term studies of small rodents.

Action Potentials↗

Long-term follow-up of symptoms, pulmonary function, respiratory muscle strength, and exercise performance after botulism.

Respiratory muscle weakness occurs commonly at presentation in patients with botulism. Although clinical improvement occurs over several months, symptoms such as fatigue and dyspnea persist in many patients in the long term. To determine whether continued respiratory muscle weakness might contribute to these symptoms, we compared lung function tests, respiratory muscle strength, and exercise performance in 13 patients 2 years after type B botulism. We found that residual symptoms including dyspnea and fatigue were common in botulism patients at 2 years postintoxication. Lung function tests had returned to normal in all patients. Maximal inspiratory and expiratory pressures were similar between botulism patients and control subjects. Evaluation of individual results showed evidence of inspiratory muscle weakness in four of 13 patients with botulism (Plmax less than 65% predicted). Maximal oxygen consumption and maximal workload during exercise were reduced in botulism patients in comparison to control subjects. During exercise, botulism patients had a more rapid and shallow breathing pattern and a higher dyspnea score at a given minute ventilation in comparison to control subjects. Reasons for premature exercise termination in botulism patients were multifactorial. Although respiratory muscle weakness may have been contributory in some patients, most appeared to be limited by reduced cardiovascular fitness, leg fatigue, or reduced motivation.

Adult↗

Maximal static respiratory pressures in the normal elderly.

To determine if a relationship exists between maximal static respiratory pressures measured at the mouth and age greater than 55 yr, and if so, whether regression equations can be derived that accurately reflect this, we measured maximal inspiratory (Plmax) and expiratory (PEmax) pressures in 64 normal women and 40 normal men older than 55 yr of age. We found no relationship between PImax and PEmax and age greater than 55 yr (all r squared values less than 0.14). We tested the reproducibility of our measurements of PImax and PEmax in 13 and 12 subjects, respectively, on three separate occasions. Repeated measures analysis showed no significant differences in these measurements. Using the measurements obtained in this large study, we calculated 95% confidence limits for PImax and PEmax values in men and women older than 55 yr of age. The 95% confidence limits for PImax in men were 55 to 161 cm H2O, and 26 to 124 cm H2O in women. The 95% confidence limits for PEmax in men were 90 to 256 cm H2O, and 46 to 184 cm H2O in women. We conclude that given the large interindividual variation, a cross-sectional study such as this or other previous studies may not be able to reveal age-dependent changes unless very large numbers are used, and even then potential for bias exists. However, with the small intraindividual coefficients of variation in repeated measurements of PImax and PEmax, a longitudinal study may provide more pertinent information.

Aged↗

Prediction of maximal oxygen uptake and power during cycle ergometry in subjects older than 55 years of age.

One hundred twenty-eight healthy volunteers (81 women, 47 men) older than 55 yr of age were studied with an incremental progressive cycle ergometer test to a symptom-limited, maximal tolerable work load. Mean (+/- SD) age was 66 +/- 6 yr in women and 66 +/- 5 years in men. Subjects with a history of ischemic heart disease, diabetes, pulmonary disease, or neuromuscular disease were excluded. Smokers were included, but all subjects had normal FEV1 and FVC. The objective of the study was to compare measured values of VO2max and Wmax in this older population with previously published predicted values based on subjects of all ages. We found that Wmax observed exceeded Wmax predicted by 9.5 +/- 22% (mean +/- SD) and that VO2max observed exceeded VO2max predicted by 17.5 +/- 22%. Because of this systematic underestimate of VO2max and Wmax by the previous prediction equations, we constructed new prediction equations for use in subjects older than 55 yr of age using height, weight, age, and sex as variables. We conclude that these new prediction equations more accurately predict Wmax and VO2max in subjects older than 55 yr of age because they are based solely on subjects in this age group.

Age Factors↗

Pathologic changes and contractile properties of the diaphragm in corticosteroid myopathy in hamsters: comparison to peripheral muscle.

Corticosteroids have been shown to produce a myopathy of peripheral skeletal muscle, characterized predominantly by Type II fiber atrophy. To determine if similar histologic and histochemical changes occur in the diaphragm and whether the in vitro contractile properties of this muscle are adversely affected by steroids, we studied two groups of hamsters. The experimental group received triamcinolone while a control group received saline, both given daily for 3 wk as i.m. injections. Soleus (Sol) and extensor digitorum longus (EDL) muscles and costal diaphragm muscle sections were stained for histologic (hematoxylin and eosin, modified Gomori trichrome) and histochemical (myosin ATPase, succinate dehydrogenase [SDH]) analysis. Muscle fiber proportions and cross-sectional areas (CSA) were measured from myosin ATPase sections. In vitro studies of isometric contractions were carried out on small strips of costal diaphragm, measuring maximal isometric twitch (Pt) and tetanus (Po) tensions, time to peak tension (TTP), half relaxation time (1/2 RT), force-frequency relationship, and fatigue characteristics (60 Hz tetani; duty cycle, 0.5). Triamcinolone treatment resulted in no change in muscle fiber proportions. There was no effect on Type I fiber CSA; however, there was Type IIa (Sol, EDL) and Type IIb (diaphragm, EDL) fiber atrophy in triamcinolone-treated animals. Pt and Po (normalized for weight) of diaphragm strips were not different. There was a prolongation in TTP and 1/2 RT, a left shift in the force-frequency curve, and a reduced fatiguability of triamcinolone-treated diaphragm (P less than 0.05). We conclude that a steroid myopathy could be explained by a loss of muscle mass (Type IIb fiber atrophy) rather than an intrinsic impairment in contractile function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An effective combination of anaesthetics for 6-h experimentation in the golden Syrian hamster.

The anaesthetics described for use in hamsters to date are suitable for the performance of short-term experimentation. However, an anaesthetic regimen was required which would provide a stable preparation for 6 h and hence, a suitable combination was developed. In the first set of experiments, the effect of anaesthetics (chloralose, urethane, and pentobarbital) were examined alone and in combination on arterial blood measurements. In the second set of experiments the effect of the combination of anaesthetics on arterial blood measurements and minute ventilation was examined for up to 6 h. Chloralose, urethane and pentobarbital when used alone in the hamster were considered inadequate for our needs. Chloralose did not produce adequate surgical anaesthesia whereas urethane and pentobarbital resulted in marked respiratory depression. Urethane also produced a trend towards metabolic acidosis. In contrast, the combination of agents resulted in surgical anaesthesia and the arterial blood measurements were adequate. Further, the use of the combination of anaesthetics in hamsters resulted in a stable preparation where arterial blood measurements and minute ventilation were maintained in a good range for up to 6 h. The combination of chloralose, urethane and sodium pentobarbital in hamsters should prove useful in long-term non-recovery experimentation which requires early surgical intervention, minimal respiratory depression and an even depth of anaesthesia.

Anesthesia↗

Respiratory muscle performance in normal elderly subjects and patients with COPD.

We studied the reproducibility of tests of RM performance in normal elderly subjects and compared their performance with that of patients with COPD. The RM strength was measured as MIP and MEP. The RM endurance was measured using a two-minute incremental threshold loading test. The max load, the average Ppk as %MIP at max load and the Pmean at max load were taken as measures of respiratory muscle endurance. The MIP, but not MEP, was less in COPD patients than in normal subjects (p less than 0.05). There was a small increase in between visits, in MIP in the normal subjects. All measures of RM endurance were much lower in the COPD group than in the normal elderly (p less than 0.05). We conclude that (1) RM strength and endurance are reproducible in normal elderly subjects and patients with COPD, (2) that COPD subjects have decreased RM strength and endurance compared with normal elderly subjects, and (3) that in COPD subjects RM endurance is compromised more than RM strength.

Aged↗

The effect of breathing frequency on inspiratory muscle endurance during incremental threshold loading.

We tested whether there were differences in measures of respiratory muscle endurance between tests with spontaneously chosen breathing patterns and tests with fixed breathing rates in normal volunteers. Measures of respiratory muscle endurance-maximum load tolerated, mean mouth pressure at maximum load and peak pressure at maximum load were reproducible over three tests with the spontaneously chosen breathing pattern. There was no difference in these measurements between the three tests with fixed breathing frequency. There was no difference in tidal volume, inspiratory time, and the ratio of inspiratory time to total breath duration between the tests in which breathing pattern was spontaneously chosen; there was a difference in these measurements between the tests with a fixed breathing frequency. We conclude that regulation of breathing frequency is unnecessary in the two-minute threshold loading test to obtain reproducible results for measures of respiratory muscle endurance.

Adult↗

Comparison of two-minute incremental threshold loading and maximal loading as measures of respiratory muscle endurance.

We performed a two-minute incremental threshold loading test (incremental test) in ten normal subjects on three occasions, and having ascertained the maximum load (max load) against which they could inspire for two minutes, measured how long this load could be tolerated by these same subjects on three further occasions (tlim test). We compared the reproducibility of the two tests. There were no significant differences found in the mean max loads in the three incremental tests, or in the endurance times in the three tlim tests. However, the intraindividual coefficients of variation of max load in the incremental test (0 to 14 percent) were much smaller than the intraindividual coefficients of variation of endurance time in the tlim test (20 to 65 percent). We found that the large variability in endurance time in our tlim tests was most likely accounted for by variability in breathing pattern, inspiratory flow rate and breath-by-breath mouth pressure generation. Differences in these parameters did not, however, explain why in the tlim test a given subject could tolerate for 19 minutes a load only 100 g less than that which he was unable to tolerate for two minutes in the incremental test. These findings emphasize the differences between these two tests of respiratory muscle endurance. Since there was less intraindividual variability in the two-minute incremental threshold loading test, we suggest that this test may be more useful than the tlim test.

Adult↗

Cardiac output at rest and in exercise in elderly subjects.

We measured cardiac output (Q), at rest and during graded exercise, in 68 women and 41 men over the age of 55 yr, using a CO2 rebreathing method. Mean (+/- SD) age was 66 +/- 5 yr in women and 66 +/- 6 yr in men. Only subjects with no history or physical examination findings of pulmonary, cardiac, neuromuscular, or endocrine disease and normal electrocardiography and spirometry were studied. We found a linear relationship between Q and oxygen uptake (VO2) in males and females. The regression equation expressing this relationship in males was Q = 2.9 + 5 VO2 1.min-1 (SEE 2.8) and, in females, Q = 2.9 + 4.6 VO2 1.min-1 (SEE 2.8). This is similar to the relationship previously estimated for elderly males using the direct Fick method and concurs with other reports in the literature which show that, while the Q-VO2 relationship in the elderly has a slope similar to that in younger groups, the Q-VO2 intercept is lower. This means that the absolute level of cardiac output for a given level of work is lower in the elderly than in younger populations. This may reflect an age-related decrease in active metabolic tissue in the elderly and/or altered metabolic regulation with increased oxygen extraction from blood.

Aged↗

Diaphragmatic relaxation rate after voluntary contractions and uni- and bilateral phrenic stimulation.

We compared the rate of relaxation of the diaphragm (RRdi) after unilateral phrenic nerve stimulation, bilateral phrenic nerve stimulations, and short sharp voluntary contractions (sniffs). RRdi was measured as the maximum rate of decline in transdiaphragmatic pressure (Pdi) corrected for the change in Pdi [maximum relaxation rate (MRR)/delta Pdi], the time constant (tau) of the later exponential decline in Pdi, and the time to half relaxation (1/2 RT). In five subjects there was no difference in mean RRdi apart from a smaller MRR/delta Pdi (P less than 0.05) for left unilateral compared with either right unilateral or bilateral needle stimulation. However, RRdi varied unpredictably between unilateral and bilateral stimulation of the phrenic nerve in individual subjects. In the same five subjects, sniffs were found to have a slower RRdi than bilateral stimulations (MRR/delta Pdi 0.0064 +/- 0.0007 vs. 0.0074 +/- 0.0018/ms, tau 57.2 +/- 8.7 vs. 48.2 +/- 7.4 ms, 1/2 RT 108.9 +/- 10.9 vs. 73.9 +/- 6.0 ms; all P less than 0.05). The application and inflation of an abdominal binder to an external pressure of 60 mmHg resulted in a decrease in functional residual capacity (-710 +/- 70 ml), but there was no effect on relaxation parameters. Our findings suggest that in the evaluation of RRdi 1) unilateral hemidiaphragmatic stimulations may not accurately reflect the in vivo contractile properties of the diaphragm, 2) sniff maneuvers are not voluntary equivalents of phrenic nerve stimulations, and 3) RRdi is not affected by abdominal binder inflation up to 60 mmHg.

Adult↗

Phrenic nerve function in patients with diaphragmatic weakness and systemic lupus erythematosus.

Diaphragmatic weakness has been identified as one of the pulmonary manifestations of systemic lupus erythematosus. Whether this weakness results from a neuropathic or myopathic process has not been established. Thirty patients with SLE were screened for the presence of inspiratory muscle (IM) weakness. Detailed studies were performed in nine with IM weakness. All nine were found to have diaphragmatic weakness (mean +/- SD, maximal transdiaphragmatic pressure 50 +/- 12 cmH2O). Phrenic nerve latencies, evaluated using transcutaneous stimulation, were normal in all individuals excluding a demyelinating neuropathy. Compound diaphragm action potential (CDAP) with phrenic nerve stimulation was normal in six of these nine patients. Reduced CDAP in three of nine patients was consistent either with axonal degeneration of the phrenic nerve or diaphragm myopathy. Nerve conduction and electromyographic studies on peripheral nerves and muscles respectively failed to demonstrate an associated generalized neuropathy or myopathy. We conclude that diaphragmatic weakness in patients with SLE is both common and is very unlikely to be caused by a phrenic neuropathy.

Action Potentials↗

Lambert-Eaton myasthenic syndrome involving the diaphragm.

Inspiratory muscle function was assessed in a patient with the Lambert-Eaton myasthenic syndrome that developed in association with a bronchogenic carcinoma. Repetitive maximal inspiratory pressure measurements and the electromyographic response to phrenic nerve stimulation established involvement of the inspiratory muscles in general and the diaphragm specifically in this condition.

Aged↗

Phrenic nerve function and its relationship to atelectasis after coronary artery bypass surgery.

Atelectasis following coronary artery bypass surgery (CAB) occurs in the majority of patients. To determine the importance of operative variables in the development of postoperative atelectasis and the incidence of phrenic nerve injury caused by topical cold cardioplegic solution, we studied 57 patients (53 male, four female) undergoing CAB. Their mean age, +/- SD, was 58 +/- 13 years. Transcutaneous stimulation was used to evaluate phrenic nerve function preoperatively and postoperatively in 52 patients. An unequivocal paresis of the phrenic nerve was documented in five patients. In an additional 27 patients, the amplitude of the compound diaphragm action potential was reduced postoperatively. However, methodologic limitations did not allow the conclusion that this was secondary to a phrenic axonal degeneration. Discriminant analysis of intraoperative variables showed more severe atelectasis with a larger number of grafts, with a longer operative and bypass time, when the pleural space was entered, when a right atrial drain and a cardiac insulating pad were not used, and with a lower body temperature. It is concluded that phrenic paresis may occur after CAB and topical cold cardioplegia, but that other factors must explain the atelectasis found in the majority of patients.

Cardioplegic Solutions↗

Dietary supplementation and respiratory muscle performance in patients with COPD.

We studied the effects of oral nutritional supplementation on respiratory muscle (RM) performance in 25 ambulatory patients with severe chronic obstructive pulmonary disease (COPD). There was a relationship between body weight and anthropometric parameters of nutritional status (triceps skinfold thickness [r = 0.67; p less than 0.005], midarm muscle circumference (r = 0.53; p less than 0.005), but body weight did not correlate with daily caloric intake, serum albumin, transferrin, or blood lymphocyte count. None of these measurements of nutritional status correlated with any measure of RM strength or endurance. In a randomized observer-blinded crossover trial, patients were allocated to one of two groups. In the first eight weeks of the study, group A received nutritional supplementation, and patients in group B were control subjects. In the second eight weeks, patients in group A were control subjects, and group B received supplement. Mean daily caloric intake and body weight increased in both groups while receiving supplement (both p less than 0.05). Calories provided by the supplement were frequently substituted for normal dietary calories. Any increases in RM performance in the group receiving supplement were matched by increases (due to learning) in controls. We conclude that oral dietary supplements have no important effects on RM performance in ambulatory patients with COPD.

Ambulatory Care↗