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Biomedical subjects

M Decramer

Publications and source records attributed to M Decramer.

At least 55 records · Page 3Linked to original sources

Reversibility of paraneoplastic bilateral diaphragmatic paralysis after nephrectomy for renal cell carcinoma.

Bilateral diaphragmatic paralysis is usually caused by anatomic lesions of both phrenic nerves (e.g., after cardiothoracic surgery), generalized neurologic diseases (e.g., primary motor neuron disease, amyotrophic lateral sclerosis) or is without a known cause (idiopathic). We report a case of a patient with renal cell carcinoma complicated by an isolated bilateral diaphragmatic paralysis without clinical or electromyographic signs of other muscle or nerve involvement. There has been progressive, though till now partial, recovery of his vital capacity rising from 44% to 72% of predicted values, and maximal inspiratory pressures during the two years following the curative resection of his renal cell carcinoma. We believe this is the first report of a paraneoplastic bilateral diaphragmatic paralysis with actual recovery after tumour therapy.

Carcinoma, Renal Cell↗

Incentive spirometry does not enhance recovery after thoracic surgery.

OBJECTIVE: To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. DESIGN: Randomized controlled trial. SETTING: University hospital, intensive care unit, and surgical department. PATIENTS: Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. INTERVENTIONS: Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. MEASUREMENTS AND MAIN RESULTS: Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay. CONCLUSIONS: Pulmonary complications after lung and esophagus surgery were relatively low. The addition of IS to PT did not further reduce pulmonary complications or hospital stay. Although we cannot rule out beneficial effects in a subgroup of high-risk patients, routine use of IS after thoracic surgery seems to be ineffective.

Analysis of Variance↗

Nandrolone decanoate does not enhance training effects but increases IGF-I mRNA in rat diaphragm.

To examine whether concomitant anabolic steroid treatment combined with training might enhance previously observed training effects (A. Bisschop, G. Gayan-Ramirez, H. Rollier, R. Gosselink, R. Dom, V. de Bock, and M. Decramer. Am. J. Respir. Crit. Care Med. 155: 1583-1589, 1997) and whether insulin-like growth factor I (IGF-I) was involved in these changes, male and female rats were submitted to inspiratory muscle training (IMT) for 8 wk (30 min/day, 5 times/wk) and were compared with untrained controls. During the last 5 wk of training, trained rats were divided to receive weekly either low-dose (LD; 1.5 mg/kg) or high-dose (HD; 7.5 mg/kg) nandrolone decanoate or saline for the IMT and control rats. In both sexes, diaphragm muscle mass and contractile properties were unchanged with treatment. In males, HD resulted in decreased diaphragm type I cross-sectional area (-15%; P < 0.05, HD vs. IMT), whereas no changes were observed in females. Finally, an increase in IGF-I mRNA levels was present in HD male (+73%; P < 0.05, HD vs. IMT) and female treated rats [LD (+58%) and HD (+96%) vs. IMT; P < 0.001]. We conclude that administration of nandrolone decanoate did not enhance the previously observed training effects in rat diaphragm, although it increased the IGF-I mRNA expression levels.

Anabolic Agents↗

Lung volume reduction surgery does not improve diaphragmatic contractile properties or atrophy in hamsters with elastase-induced emphysema.

It is claimed that lung volume reduction surgery (LVRS) improves inspiratory muscle function. As diaphragm structure and function are not directly appraisable in patients, we studied the effects of LVRS on the diaphragm in vitro contractile properties and morphology in hamsters with elastase-induced emphysema. Four months after intratracheal instillation of elastase (40 U/100 g), hamsters underwent either bilateral LVRS (LVRS, n = 11) or a sham operation (SHAM, n = 8). Four animals died during the perioperative period in LVRS (n = 7). Hamsters instilled with saline served as control (CTL, n = 8). Animals were studied at the age of 9 mo. LVRS was associated with a significant 25% decrease in functional residual capacity compared to SHAM (p < 0.05). Compared with CTL, LVRS and SHAM showed a significant 18% and 14% reduction in diaphragm mass, respectively (p = 0.02). LVRS had a significantly decreased twitch tension compared to CTL and SHAM (p < 0.01). Both LVRS and SHAM showed increased resistance to muscle fatigue compared with CTL. The histochemical analysis revealed a significant shift from type IIx/b toward type IIa fibers in LVRS and SHAM compared with CTL. In conclusion, emphysema is associated with functional adaptations but LVRS does not appear to beneficially alter the diaphragm contractile and morphological characteristics in hamsters with elastase-induced emphysema.

Animals↗

[Clinical relevance of myosin isoforms in the diaphragm].

The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy, denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.

Adaptation, Physiological↗

Regulation of mucociliary clearance in health and disease.

Airway secretions are cleared by mucociliary clearance (MCC), in addition to other mechanisms such as cough, peristalsis, two-phase gas-liquid flow and alveolar clearance. MCC comprises the cephalad movement of mucus caused by the cilia lining the conducting airways until it can be swallowed or expectorated. MCC is a very complex process in which many variables are involved, all of which may modify the final outcome. The structure, number, movement and co-ordination of the cilia present in the airways as well as the amount, composition and rheological properties of the periciliary and mucus layers are determinants of MCC. Physiological factors such as age, sex, posture, sleep and exercise are reported to influence MCC due to a change in the cilia, the mucus or the periciliary layer, or a combination of these. Environmental pollution is suspected to have a depressant effect on MCC dependent on different factors such as pollutant concentration and the duration of exposure. Most studies focus on sulphur dioxide, sulphuric acid, nitrogen dioxide and ozone. Tobacco smoke and hairspray have been noted to have a negative influence on MCC. Some diseases are known to affect MCC, mostly negatively. The underlying mechanism differs from one illness to another. Immotile cilia syndrome, asthma, bronchiectasis, chronic bronchitis, cystic fibrosis and some acute respiratory tract infections are among the most frequently reported. The present paper reviews normal mucociliary clearance and the effects of diseases on this process.

Ciliary Motility Disorders↗

Six minute walking distance in healthy elderly subjects.

The six minute walking distance (6MWD) test is a commonly used test to estimate functional exercise capacity in patients with chronic diseases including chronic obstructive lung disease. Surprisingly, no attempt has been made to establish normal values for the 6MWD. The aim of this study, therefore, was to evaluate the 6MWD in healthy elderly volunteers and to evaluate its determining factors. Fifty-one healthy subjects aged 50-85 yrs volunteered to participate in the trial. All subjects were free of diseases that could interfere with performance in a walking test. Tests were performed in a quiet 50-m long hospital corridor. Patients were encouraged every 30 s to continue walking as quickly as possible. Walking distance averaged 631+/-93 m and was 84 m greater in the male compared to female subjects (p<0.001). The 6MWD showed significant correlations with age (r=-0.51, p<0.01) and height (r=0.54, p<0.01). Stepwise multiple regression analysis showed that age, height, sex and weight were independent contributors to the 6MWD in healthy subjects, thus explaining 66% of the variability. It is concluded that the six minute walking distance can be predicted adequately using a clinically useful model in healthy elderly subjects. Its variability is explained largely by age, sex, height and weight. Results of the six minute walking distance may be interpreted more adequately if expressed as a percentage of the predicted value.

Aged↗

Effects of drugs on mucus clearance.

Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which is a quaternary ammonium compound, has been suggested to decrease CC significantly. Bromhexine, ambroxol and neutral saline seemed not to alter CC, either positively or negatively. Finally, treatment with either amiloride, recombinant human deoxyribonuclease, bromhexine, ambroxol, N-acetylcysteine, S-carboxymethylcysteine or hypertonic saline has been suggested as a possible cause of clinical improvement in patients, such as the experience of dyspnoea, the case of expectoration or the frequency of infective exacerbations. Other agents did not show a clinical benefit.

Animals↗

Acute treatment with corticosteroids decreases IGF-1 and IGF-2 expression in the rat diaphragm and gastrocnemius.

Massive doses of methylprednisolone (M) or triamcinolone (T) induced diaphragmatic type IIx/b atrophy, resulting in a leftward shift of the force-frequency curve in rats (). To examine the role of insulin-like growth factors (IGFs) in these changes, IGF mRNA content was measured in costal diaphragm, gastrocnemius, and liver removed from 32 rats treated daily during 5 d either with saline (control, C and pair-fed, PF), M, or T (80 mg/kg). Blood samples were taken to measure IGF-1 serum levels. RNA levels were measured by Northern and dot-blots after hybridization with rat IGF-1 or IGF-2 cDNA probes labeled with alpha-32P. Compared with C (845 +/- 128 ng/ml), IGF-1 serum levels were significantly decreased in M (699 +/- 90 ng/ml, p < 0.001 versus C) and PF animals (505 +/- 33 ng/ml, p < 0.001 versus others) and even more so, in T-treated animals (273 +/- 134 ng/ml, p < 0.001 versus others). Along the same lines, IGF-1 expression in the liver was depressed after corticosteroid treatment and in PF, whereas IGF-2 mRNA content remained unchanged. Compared with C, the relative expression of IGF-1 mRNA in the diaphragm was depressed by 44% and 69% in the M and T groups, respectively (p < 0.0001 versus C), while it was unchanged in PF animals. In the gastrocnemius, IGF-1 expression was reduced after M and T (-51% and -59%, respectively, p < 0.0001 versus C) as well as in PF animals (-40%, p < 0.001 versus C). For IGF-2, a similar pattern of expression was found in the diaphragm and the gastrocnemius. Indeed, IGF-2 mRNA tended to decrease in corticosteroid-treated rats (NS) whereas it was unchanged in PF rats. We conclude that decreased IGF expression after corticosteroid treatment was similar in diaphragm and gastrocnemius and may be responsible for the diaphragmatic changes observed after steroid treatment.

Animals↗

Effects of dilated cardiomyopathy on the diaphragm in the Syrian hamster.

This study aimed to elucidate changes in respiratory muscles and their mechanism in cardiomyopathy. The contractile properties and histology of the diaphragm, as well as serum levels of insulin-like growth factor (IGF)-1, were examined in 10 hamsters with idiopathic dilated cardiomyopathy (CM) and 10 controls. At 28 weeks, body weight in CM was reduced compared with controls (114+/-10 versus 144+/-14 g, p<0.0001). The ratio of diaphragm to body weight was significantly higher in CM than in controls (0.228+/-0.015 versus 0.182+/-0.017, p<0.0001). In vitro, maximal diaphragmatic twitch (303+/-63 versus 455+/-119 g x cm(-2)) and tetanic tensions (1,555+/-369 versus 2,204+/-506 g x cm(-2)) were significantly lower in CM than in controls (p<0.005). The half-relaxation time was significantly shorter in CM (19+/-1 ms) than in controls (24+/-3 ms, p<0.0005). Fatiguability at 25 Hz was significantly less in CM (28%) than in controls (42%, p<0.0001). Diaphragm and gastrocnemius adenosine triphosphatase staining showed type I fibre atrophy in CM, associated with an increase in the number of type I fibres in the diaphragm. Histological examination of both muscles revealed an abnormal muscular pattern. Finally, serum levels of IGF-1 were 47% lower in the CM group than in controls (p<0.0001) and were clearly related to the changes in the contractile properties and histology of the diaphragm. In conclusion, cardiomyopathy in hamsters: 1) depressed the force-generating capacity and shortened the relaxation of the hamster diaphragm; 2) induced type I fibre atrophy in combination with a myopathic pattern; and 3) was associated with a significant reduction in serum levels of insulin-like growth factor-1, related to the diaphragmatic changes. Whether these changes are primary myopathic or secondary to heart failure remains to be elucidated.

Adenosine Triphosphatases↗

Respiratory muscle involvement in multiple sclerosis.

Respiratory complications are common in the terminal stages of multiple sclerosis and contribute to mortality in these patients. When respiratory motor pathways are involved, respiratory muscle weakness frequently occurs. Although it is well established that weakness of the respiratory muscles produces a restrictive ventilatory defect, the degree of muscle weakness and pulmonary function are poorly related. Respiratory muscle weakness was observed in patients with normal or near normal pulmonary function. Expiratory muscle weakness is more prominent than inspiratory muscle weakness and may impair performance of coughing. Subsequently, in addition to bulbar dysfunction, respiratory muscle weakness may contribute to ineffective coughing, pneumonia, and sometimes even acute ventilatory failure may ensue. Respiratory muscle weakness may also occur early in the course of the disease. Recent studies suggest that the respiratory muscles can be trained for both strength and endurance in multiple sclerosis patients. Whether respiratory muscle training delays the development of respiratory dysfunction and subsequently improves exercise capacity and cough efficacy, prevents pulmonary complications or prolongs survival in the long-term remains to be determined.

Humans↗

Physiological basis of improvement after lung volume reduction surgery for severe emphysema: where are we?

Lung volume reduction surgery has become an accepted therapeutic option to relieve the symptoms of selected patients with severe emphysema. In a majority of these patients, it causes objective as well as subjective functional improvement. A proper understanding of the physiological determinants underlying these beneficial effects appears very important in order to better select patients for the procedure that is currently largely carried out on an empirical basis. Lung volume reduction surgery has two distinct effects. Firstly, it causes an increased elastic recoil, which at least partially explains the enhanced maximal expiratory flow. Secondly, it is associated with a reduction of hyperinflation which allows for an increase in global inspiratory muscle strength and in diaphragmatic contribution to tidal volume as well as a decrease in the inspiratory elastic load imposed by the chest wall. Taken together, these effects result in a reduced work of breathing and in an enhanced maximal ventilation which both contribute to the increased exercise capacity and reduced dyspnoea after surgery. The improved lung recoil and the reduced hyperinflation after volume reduction surgery were the primary postulates upon which the usual selection criteria for the procedure were based. It is now likely that these are correct. Nevertheless, some patients do not benefit from lung volume reduction surgery and the current literature does not allow for a refinement of the selection process from a physiological point of view. The exact mechanisms underlying the improvement in lung recoil, lung mechanics, and respiratory muscle function remain incompletely understood. Moreover, the effects of lung volume reduction surgery on gas exchange and pulmonary haemodynamics still need to be more fully investigated. An analysis of the characteristics of patients who do not benefit from the procedure and the development of an animal model for lung volume reduction surgery would probably help address these important issues.

Exercise Tolerance↗

Physical performance of patients with numerous psychosomatic complaints suggestive of hyperventilation.

In some patients exercise induces numerous complaints which cannot be attributed to an organic disorder, and which are suggestive of hyperventilation. The study was designed to investigate in this type of patient: 1) exercise capacity and muscle force; 2) breathing pattern and symptoms during maximal exercise and recovery; 3) relationships between symptoms and breathing pattern. Twenty-four patients were compared with 20 healthy subjects. They performed a maximal incremental cycle ergometer test and peripheral and respiratory muscle strength were measured. Patients tended to have a decreased exercise capacity and presented with moderately reduced muscle strength. At comparable minute ventilation, breathing frequency was higher (mean: 24 versus 21 per minute) and tidal volume smaller (mean: 1.42 versus 1.67 L). End-tidal partial pressure of carbon dioxide (PET,CO2) was not significantly different. A significant relation was observed between PET,CO2 and respiratory frequency during recovery in patients, suggesting a reduced flexibility of the ventilatory response to exercise. In patients respiratory complaints and paresthesias were weakly correlated to PET,CO2 at moderate exercise. It is suggested that the physical deconditioning observed in those patients is rather a consequence than a cause of the response to exercise. The link between symptoms and breathing pattern might be explained by a psychological conditioning process.

Adult↗

Biliary cirrhosis induces type IIx/b fiber atrophy in rat diaphragm and skeletal muscle, and decreases IGF-I mRNA in the liver but not in muscle.

BACKGROUND/AIMS: Patients with cirrhosis complain of fatigue, which in part may be due to the progressive muscle atrophy, noted especially when signs of decompensation appear. In addition, weaning from mechanical ventilation may be difficult in some patients following liver transplantation. Since little is known about the peripheral muscles and the diaphragm in cirrhosis, we investigated diaphragm and gastrocnemius histochemical properties, and diaphragm contractile properties in male rats with biliary cirrhosis. In addition, the extent to which insulin-like growth factor I (IGF-I) was involved in the regulation of muscle function was also examined, since IGF-I is known to induce growth and regeneration as well as to exert a protein anabolic action. METHODS: Ten rats underwent a sham operation, while another ten underwent bile duct ligation and excision. After 5 weeks, biliary cirrhosis was confirmed histologically in random liver biopsies. RESULTS: Compared to sham animals, diaphragm mass in cirrhotic rats was decreased by 10% (p<0.05), while masses of other respiratory (e.g. scalenus medius -21%, p<0.001) or peripheral muscles (e.g. gastrocnemius -24%, p<0.0001) decreased more. No changes in diaphragm force nor in its endurance were observed between the two groups. However, a clear decrease in the cross-sectional area of type IIx/b muscle fiber was present in both diaphragm (1360+/-147 vs 1112+/-167 microm2, p<0.02) and gastrocnemius (1954+/-265 vs 2328+/-245 microm2, p<0.02). Finally, hybridization of Northern blot with a rat cDNA IGF-I probe (gift from Dr D. Leroith, Bethesda, USA) labeled with alpha-32P revealed that in cirrhotic rats, the relative expression of IGF-I was markedly reduced by 45% in the liver (p<0.05) but was unchanged in the two muscles studied. CONCLUSIONS: In this model of biliary cirrhosis: (i) muscle wasting was less pronounced in the diaphragm than in other muscles; (ii) type IIx/b fiber atrophy in respiratory (diaphragm) and peripheral muscles (gastrocnemius) developed while diaphragm contractile properties remained unchanged; and (iii) the relative expression of IGF-I was reduced in the liver only, while it remained unchanged in the muscle. The functional significance of these changes, their pathogenesis and presence in other models and in human cirrhosis remain to be elucidated.

Animals↗

Contractile properties and histochemical characteristics of the rat diaphragm after prolonged triamcinolone treatment and nutritional deprivation.

The influence of decreased muscle mass and reduced food intake on diaphragm structure and contractility in male Wistar rats was determined after triamcinolone acetate treatment (TR: 0.5 mg per kg per day for 4 weeks) and two degrees of undernutrition (PW: pair-weight, which resulted in a similar (41%) reduction of body weight as TR; PF: pair-fed, which resulted in a moderate (13%) reduction of body weight) and a free-fed control group (FF, with an increase (9%) in body weight). energy intake of TR decreased, but based on daily measurements of food intake and body weight, energy expenditure of the TR rats was increased compared with the other groups. Body (BW) and muscle weights were reduced in proportion to the extent of undernutrition in the nutritionally deprived rates (i.e. BW and diaphragm weight of PF animals were reduced 215 and 16% respectively compared with FF, v. a. 48% and 41% reduction in the PW group). Triamcinolone-induced atrophy was limited to type II fibres (30% of type IIa and 45% of type IIx/b, p < 0.05), while severe chronic undernutrition (PW) induced a generalized fibre type atrophy in the diaphragm (23% type I, 38% type IIa and 49% type IIx/b, p < 0.05), and moderate undernutrition (PF) caused only significant type IIa atrophy (20%, p < 0.05). A leftward shift of the diaphragmatic tension-frequency relationship and a decreased fatiguability of the TR and PW bundles were observed (p < 0.01), while the PF bundles were not significantly different compared with FF. These results suggest that triamcinolone and severe undernutrition cause similar alterations in in vitro contractility of the diaphragm. The effects of triamcinolone treatment on diaphragm structure may be partly explained by the reduced food intake, but the atrophy pattern induced by severe undernutrition (PW) was different.

Age Factors↗

Low load inspiratory muscle training increases diaphragmatic fiber dimensions in rats.

The effects of 8 wk of inspiratory resistive loading (30 min/d, 3 x/wk) on diaphragm mass, contractile properties, fatigue, and fiber dimensions were studied in 10 male Wistar rats. They were conditioned to breathe through a Hans-Rudolph device. Half of them had to overcome a moderate inspiratory resistance (MR; n = 5), whereas the others only had to overcome the small resistance (SR; n = 5) of the inspiratory valve of the device. Results were compared with control rats (C; n = 5) moving and breathing freely. At the end of training, animals submitted to MR and SR generated mean inspiratory pressures of -2.5 +/- 1.1 and -0.2 +/- 0.05 cm H2O, respectively. TI/Ttot was 0.60 +/- 0.06 and 0.57 +/- 0.05, respectively. Body and diaphragm weight were unaffected by loading. Little or no change in in vitro diaphragmatic twitch kinetics, force generation, and fatigability was found between the three groups. Nevertheless, cross-sectional area of all fiber types increased in the two loaded groups compared with control animals. This increase reached statistical significance for type I fibers in the MR group (846 +/- 74 microm2) compared with the C and SR groups (589 +/- 32 and 683 +/- 96 microm2, respectively, p < 0.05). For IIa fibers both training groups were significantly different from the control group (SR: 768 +/- 99 and MR: 790 +/- 108 versus C: 592 +/- 37 microm2, p < 0.05). A hypertrophy of type IIx/b fibers was seen in MR compared with control animals (C: 1,555 +/- 136, SR: 1,845 +/- 338, MR: 2,053 +/- 326 microm2, p < 0.05). No differences were present in fiber type proportions between the three groups. We conclude that in our training setup, 8 wk of intermittent long-term inspiratory loading stressed the diaphragm already with a small resistance resulting in hypertrophy of predominantly type IIa fibers. A higher resistance resulted in hypertrophy of all fiber types.

Animals↗

Systolic ventricular dysfunction causes selective diaphragm atrophy in rats.

In order to examine the relative impairment of the diaphragm and other skeletal muscles in systolic ventricular dysfunction (VD), their structure and function were compared between rats with VD induced by left coronary artery ligation (n = 17) and sham-operated rats (Co, n = 10). In addition, in an attempt to unravel the mechanism of the observed impairment, we examined alterations in insulin-like growth factor-I (IGF-I) serum levels and IGF-I expression in the liver, diaphragm, and gastrocnemius. In a second series of rats (VD, n = 5 and Co, n = 5) hemodynamic measurements were performed. All measurements were performed 3 mo after the operation. Infarct size averaged 32 +/- 10 and 44 +/- 20% in the two series, respectively (NS). Hemodynamic measurements revealed a decrease in left ventricular peak systolic pressure of 19% (p < 0. 05). Significant diaphragm atrophy (weight: 622 +/- 52 mg in VD versus 750 +/- 54 mg in Co, p < 0.0005), without alterations in diaphragm contractile properties was present in VD animals. For all animals combined, the reduction in diaphragm weight was related to infarct size (r = -0.74, p < 0.001). No alterations were observed in the other inspiratory and peripheral muscles. ATPase staining of the diaphragm showed atrophy of type I and type IIx/b fibers, their cross-sectional area (CSA) being reduced by 13 and 16%, respectively (p < 0.05). There were no signs of myopathic alterations. IGF-I expression was increased by 55% in the diaphragm of rats with VD (p < 0.05). IGF-I expression in the liver and gastrocnemius and serum IGF-I levels were unaltered. These data suggest the presence of compensatory mechanisms aimed at minimizing diaphragmatic fiber atrophy. We conclude that systolic VD caused: (1) selective diaphragm atrophy, which was related to infarct size; (2) a decrease in diaphragm type I and IIx/b CSA not associated with myopathic changes; (3) an increase in the IGF-I mRNA content of the diaphragm. The selective diaphragm involvement in the present study may be related to the moderate degree of ventricular dysfunction induced.

Adenosine Triphosphatases↗