Biomedical subjects

G Gayan-Ramirez

Publications and source records attributed to G Gayan-Ramirez.

At least 19 recordsLinked to original sources

PubMed2000

Corticosteroids decrease mRNA levels of SERCA pumps, whereas they increase sarcolipin mRNA in the rat diaphragm.

1. In order to explore the potential role of the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA)-type pumps and of their modulators phospholamban (PLB) and sarcolipin (SLN) in the functional alterations of the diaphragm induced by corticosteroid treatment, expression of SERCA, PLB and SLN was assessed by RT-PCR in the diaphragm of rats treated daily for 5 days either with triamcinolone (80 mg kg-1, n = 8) or with saline (control; 0.6 ml, n = 8). 2. Triamcinolone treatment reduced the normalised overall amount of all SERCA mRNA in diaphragm by 70 % compared to controls (P < 0.05). This reduction was accounted for by a relatively larger decrease in the SERCA1 mRNA (-69 %, P < 0.05) whilst the decrease in SERCA2 mRNA (-49 %, P = 0.09) did not reach statistical significance. As a result the relative proportion of SERCA2 mRNA was increased from 43 +/- 7 % in control diaphragm to 52 +/- 4 % after triamcinolone treatment (P < 0.05). 3. Only the adult isoform of SERCA1 (i.e. SERCA1a) mRNA was found in the diaphragm of the 15-week-old control rats. Furthermore, triamcinolone treatment resulted in reduced levels of SERCA2a (-40 %, P < 0.05) and increased levels of SLN mRNA (+100 %, P < 0.05), while the decrease in PLB mRNA (-31 %, P = 0.277) did not reach statistical significance. SERCA1b, SERCA2b and SERCA3 mRNA levels fell below the detection limit in the diaphragm of both control and triamcinolone-treated rats. 4. Compared to control diaphragm, control rat heart showed a relatively high PLB/(SERCA1 + SERCA2) mRNA ratio of 7.88 while this ratio amounted only to 0.16 in control extensor digitorum longus (EDL) muscle. Remarkably, the SLN/(SERCA1 + SERCA2) mRNA ratio in normal cardiac muscle (0.96) was nearly the same as in diaphragm, but in EDL it amounted to only 0.05 that in diaphragm. This indicates the very low expression of SLN in rat EDL. 5. These data reveal that considerable alterations in SERCA mRNA levels accompany the functional changes seen in diaphragm after corticosteroid treatment. The relatively larger decrease in SERCA1 mRNA is in agreement with the selective type II fibre atrophy previously observed in the diaphragm of triamcinolone-treated rats, but the magnitude of SERCA alterations is more pronounced than expected on the basis of the structural changes in the diaphragm. The increase in SLN mRNA levels may represent a compensatory mechanism.

Adrenal Cortex Hormones↗

PubMed2000

Different effects of corticosteroid-induced muscle wasting compared with undernutrition on rat diaphragm energy metabolism.

An important adverse effect of corticosteroid treatment is respiratory muscle weakness with diaphragm muscle wasting, but little is known about the underlying pathophysiological processes involved. In order to differentiate between the effects of nutrition depletion and corticosteroids on diaphragm muscle metabolism, a study was performed to investigate the effects of triamcinolone (TR) for 2 weeks and of chronic undernutrition in a pair-weight (PW) group on the structure and energy metabolism of the diaphragm in male Wistar rats compared with a free-fed (FF) group. Diaphragm mass was reduced in TR and PW rats to a similar degree, but the extent of type-IIx/b atrophy was more pronounced in TR rats than in PW rats. No myopathic features were observed after either treatment. ATP in absolute terms as well as the ATP/ADP ratio, total adenine nucleotides, the phosphocreatine (PCr) level and the ratio between PCr and creatine (PCr/Cr) were decreased in the diaphragm of both TR and PW rats. In contrast to the PW group, the total Cr pool was reduced and pyruvate and lactate levels were elevated in the diaphragm of the TR group compared with the FF group. In conclusion, the results of this study indicate that severe undernutrition causes a decrease in muscle energy status resulting in a new metabolic equilibrium, while chronic low-dose TR treatment (0.25 mg/kg per day i.m.) causes a decrease in muscle energy status together with a mismatch between glycolysis and oxidative metabolism.

Adrenal Cortex Hormones↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

[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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

[The effect of corticotherapy on respiratory muscles].

Skeletal muscle myopathy is one of the main side-effects of systemically administered corticosteroids, and involves respiratory as well as peripheral muscles. After prolonged treatment with moderate doses of either fluorinated or non-fluorinated corticosteroids, chronic myopathy may occur. In patients, such myopathy is characterized by the gradual onset of proximal limb muscle weakness and a sudden increase in creatine excretion in 24h urine. This myopathy is associated with a generalized fiber atrophy of the quadriceps in which myopathic changes are present. Since these changes were also observed in animal models, it was concluded that steroid treatment was responsible for them. After cessation of treatment, recovery of muscle force occurs but may be protracted. The severity of corticosteroid-induced myopathy appears to depend upon the type of steroid used, the treatment duration, the dose and the treatment regimen where repetitive burst treatment effects are worse than those obtained with continuous treatment with the same dose. During short-term treatment with massive doses of corticosteroids as frequently used to treat status asthmaticus, acute myopathy may develop and is characterized by generalized fiber necrosis and rhabdomyolysis. Because such necrosis was not observed in animal studies, it was suggested that the necrosis may result from the combined effect of corticosteroids with other agents such as aminoglycoside antibiotics and/or muscle relaxants.

Adrenal Cortex Hormones↗

PubMed1997

Effects of nandrolone decanoate on respiratory and peripheral muscles in male and female rats.

Thirty male and 18 female adult rats received weekly an intramuscular injection of either saline (control; C), 1.5 mg/kg (low-dose; LD) nandrolone decanoate or 7.5 mg/kg (high-dose; HD) nandrolone decanoate during 5 wk. Compared with respective C, growth rate was stunted in male HD rats from 2 wk of treatment on, whereas it was enhanced in female LD and HD rats after 1 wk. Mass of all muscles studied varied proportionally to body weight, except for the gastrocnemius (males: 0.49 +/- 0.04 vs. C: 0.52 +/- 0.03%, not significant; females: 0.17 +/- 0.01 vs. C: 0.15 +/- 0.01%, P < 0.05). In vitro contractile and fatigue properties of the diaphragm remained unchanged, except for a decrease in twitch kinetics (time to peak tension: C, 21 +/- 2; LD, 19 +/- 1; HD, 19 +/- 2 ms, P < 0.05; half-relaxation time: C, 26 +/- 5, LD, 25 +/- 5, HD, 23 +/- 3 ms, P < 0.01). Histochemistry of the diaphragm and the gastrocnemius revealed a significant increase in type IIx/b dimensions. In the gastrocnemius, type I fiber dimensions also increased. A pair-fed study, including another 24 female rats, showed that the changes in oral food intake only partly accounted for the observed anabolic effects.

Anabolic Agents↗

PubMed1997

Broxaterol increases force output of fatigued canine diaphragm more than salbutamol.

We previously demonstrated that broxaterol enhanced recovery of fatigued canine diaphragm. The aim of this study was to compare the inotropic effects of salbutamol and broxaterol on fatigued canine diaphragm. Low-frequency fatigue was induced in 14 mongrel dogs by electrophrenic stimulation, which was continued until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced by 50% or for 1 h. After stabilization of fatigue, the animals received a bolus (18.5 microg/kg) of either broxaterol or salbutamol, followed by a continuous infusion (0.43 microg/kg/min). A second bolus of 74.0 microg/kg, followed by a continuous infusion of 1.72 microg/kg/min, was given after 90 min. Both drugs significantly increased twitch Pdi. Twitch Pdi measured 90 min after the first and second doses of broxaterol increased by 28 +/- 23% and 42 +/- 34%, respectively, whereas the salbutamol-induced increase was clearly smaller (9 +/- 10% and 17 +/- 15%, respectively). Broxaterol increased Pdi at 20 Hz by 25 +/- 28% with the first dose and by 29 +/- 21% with the second dose. In contrast, salbutamol did not alter Pdi at 20 Hz. Neither drug affected Pdi at 100 Hz. We conclude that broxaterol promoted recovery of low-frequency fatigue of the canine diaphragm in vivo in a dose-dependent manner, whereas salbutamol only minimally improved force production by the fatigued diaphragm.

Adrenergic beta-Agonists↗

PubMed1997

Intermittent inspiratory muscle training induces fiber hypertrophy in rat diaphragm.

The effects of 8 wk of moderate load intermittent inspiratory resistive loading on diaphragm contractility, and histochemistry of the diaphragm, scalenes, and gastrocnemius were studied in rats. A resistance was placed in the inspiratory port of a Hans-Rudolph valve, through which each animal breathed during 30 min/d, 5 times/wk (loaded group, n = 10). These rats were compared with animals breathing through the same device without inspiratory resistance (control group, n = 10). During loading, animals generated mean inspiratory pressures of -3.2 +/- 1.7 cm H2O with a TI/Ttot of 0.69 +/- 0.06, resulting in a tension-time index of 0.050. At the end of training, the diaphragm mass increased in loaded animals (0.17 +/- 0.01% body mass) compared with control animals (0.15 +/- 0.01%, p < 0.01), while scalene and gastrocnemius mass remained unchanged. Diaphragmatic force as well as fatigue resistance were similar in both groups, whereas time to peak tension was significantly (p < 0.01) shorter in loaded rats (18.8 +/- 1.7 ms) compared with control rats (21.2 +/- 1.8 ms), half-relaxation time remaining unchanged. Finally, hypertrophy of diaphragmatic type IIa (+19%, p < 0.01) and IIx/b (+12%, p < 0.05) was present in the loaded group. Histochemistry of the scalenes remained unchanged, whereas type IIx/b hypertrophy (+12%, p < 0.001) was observed in the gastrocnemius internus. We speculate that the latter was due to multiple escape maneuvers. We conclude that intermittent inspiratory muscle training: (1) caused fast twitch fiber hypertrophy in the diaphragm; (2) did not produce any effect in the scalenes.

Adaptation, Physiological↗