Biomedical subjects

G Gayan-Ramirez

Publications and source records attributed to G Gayan-Ramirez.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1996

On the mechanism of the mediolateral gradient of parasternal activation.

Recent studies have shown that in spontaneously breathing dogs the parasternal intercostals are activated according to a mediolateral gradient. To assess the mechanism of this regionalization of activity, we assessed the pattern of activation of these muscles after section of the dorsal roots and examined the topographic distribution of the muscle fiber types from the sternum to the chondrocostal junctions. The pattern of parasternal activity after dorsal rhizotomy was similar in all respects to that previously observed in intact animals. Thus activity in the medial parasternal bundles at the onset of inspiration frequently preceded activity in the middle bundles, and no activity was recorded from the lateral bundles. The amount of medial activity, when expressed as a percentage of the activity recorded during supramaximal tetanic stimulation of the internal intercostal nerve (maximal activity), was also consistently greater than the amount of middle activity (52.6 +/- 4.6 vs. 23.1 +/- 2.6% maximal activity; P < 0.001). Furthermore, the medial, middle, and lateral parasternal bundles had a higher proportion of slow-twitch oxidative fibers than of fast-twitch oxidative-glycolytic fibers; no topographic difference in fiber type distribution was observed. We conclude, therefore, that the mediolateral gradient of parasternal activity is probably due to the unequal distribution of central inputs throughout the pool of alpha-motoneurons.

Animals↗

PubMed1996

Recovery of corticosteroid-induced changes in contractile properties and morphology of rat diaphragm.

Treatment with the fluorinated steroid triamcinolone (TR) induced type IIb fiber atrophy and the contractile profile of a slow muscle in rat diaphragm. In contrast, the nonfluorinated steroid prednisolone (PR) caused myogenic changes without fiber atrophy, and increased fatigability. The aim of the present study was to investigate the extent to which these changes were reversed 2 mo after discontinuation of treatment. Adult rats were randomly assigned to receive saline, PR 1.25 or 5 mg/kg, or TR 0.25, 0.5, or 1 mg/kg, intramuscularly daily during 4 wk. Administration of TR resulted in severe loss of body weight and dose-dependent mortality. During recovery, body weight in the TR groups increased gradually, still remaining reduced compared with the other groups. Two months after discontinuation of treatment, diaphragm weight was increased in proportion to body weight. Twitch characteristics, maximal tetanic force, force-frequency curve, and fatigue resistance of isolated diaphragm bundles were similar in all groups. Histologic examination of the diaphragm revealed no gross abnormalities in the PR and TR groups. Mild but significant type IIb fiber atrophy was still present in the diaphragm and gastrocnemius muscle of all TR-treated animals. In conclusion, recovery of alterations in morphology of respiratory and peripheral skeletal muscles induced by administration of TR is prolonged.

Animals↗

PubMed1996

Effects of acute steroid administration on ventilatory and peripheral muscles in rats.

Occasional case reports have shown that acute myopathy may occur in patients treated with massive doses of corticosteroids. The mechanism of this myopathy is poorly understood. Therefore, 60 male rats were randomly assigned to receive daily injection of saline (C), methylprednisolone (M), or triamcinolone (T) 80 mg/kg/d for 5 d. Nutritional intake, measured daily in 15 animals, showed a significant reduction of food intake in the steroid-treated groups (-50 and -79% in M and T, respectively). This was associated with a similar loss in body weight. In the 45 remaining animals, diaphragm contractility and histopathologic features of several muscles were studied. Weights of respiratory and peripheral muscles were similarly decreased after steroid treatment. Maximal twitches of the diaphragm were lower in the C group (653 +/- 174 g/cm(2)) than in the M group (837 +/- 171 g/cm(2); p < 0.05) and the T group (765 +/- 145 g/cm(2), NS). Half-relaxation time was prolonged in both steroid groups, and time to peak tension was longer with M, whereas tetanic tensions were similar. Steroid treatment also induced a leftward shift of the force-frequency curve at 25 and 50 Hz when compared with saline treatment (p < 0.05). ATPase staining of the diaphragm, scalenus medius, and gastrocnemius showed type IIb fiber atrophy in the steroid groups and also diaphragmatic type IIa atrophy with T, whereas histologic examinations revealed a normal muscular pattern with absence of necrosis. Finally, a pair-fed (PF) study, performed in 18 rats (C, T, and PF), showed that muscle atrophy was considerably less pronounced in PF animals than in T-treated animals. We conclude that (1) short-term treatment with massive doses of steroids induced severe respiratory and limb muscle wasting; (2) both types of steroids induced predominantly type IIb atrophy, resulting in the expected alterations in diaphragm contractile properties; (3) neither steroid caused muscle necrosis; (4) type IIb atrophy was not caused by acute nutritional deprivation alone.

Adrenal Glands↗

PubMed1995

Corticosteroid treatment and nutritional deprivation cause a different pattern of atrophy in rat diaphragm.

Triamcinolone (TR) causes type IIb fiber atrophy in the rat diaphragm, which is associated with changes in contractile properties. We investigated whether this is a direct effect of TR or the result of an accompanying loss of body and diaphragm weights. For 6 wk, adult rats received saline intramuscularly, TR (0.5 mg/kg im), or nutritional depletion (ND) that resulted in a similar (approximately 40%) reduction in body weight as TR. In these animals, the half-relaxation time of the diaphragm bundles increased, the force-frequency relationship shifted leftward, and the resistance to fatigue was increased. No histological changes were found in the ND diaphragm, in contrast to severe myogenic alterations in the TR diaphragm. Type IIb fiber cross-sectional area (CSA) in the TR diaphragm was reduced by 51%, whereas type I and IIa CSAs were unaffected. In the ND animals, the CSAs of type I, IIa, and IIb fibers were reduced by 31, 33, and 52%, respectively. Similar changes occurred in the deep part of the m. gastrocnemius. In conclusion, myogenic changes and selective type IIb fiber atrophy were caused by TR, whereas ND induced generalized fiber type atrophy without histological changes.

Adrenal Cortex Hormones↗

PubMed1995

Mechanism of theophylline-induced inotropic effects on foreshortened canine diaphragm.

The mechanisms of theophylline-induced inotropic effects at shorter diaphragm length have not yet been explored. We wondered whether the greater inotropic effects of the drug at shorter diaphragm length might result from an effect on intracellular calcium level. Forty pairs of diaphragm bundles were stimulated at 70% of optimal length in the presence of either verapamil (10(-5)M), calcium-free Krebs solution (buffered or not with 2 mM ethylene glycol tetra-acetic acid (EGTA)) or ryanodine (10(-6) M). Theophylline (1 mM) was subsequently added to one muscle bundle and, after 15 min, twitches were repeated. The twitch potentiation induced by theophylline (37 +/- 21%) was unaffected by verapamil (43 +/- 26%), or zero calcium (39 +/- 18%) and virtually unchanged when the latter was buffered with EGTA. By contrast, theophylline failed to increase twitch tension after pretreatment with ryanodine, a blocker of the calcium release by the sarcoplasmic reticulum. This decreased twitch tension in control (-5 +/- 11%) and experimental (-14 +/- 12%) bundles and prolonged half-relaxation time as a result of impaired sarcoplasmic reticulum calcium reuptake. We conclude that the inotropic effects of theophylline on twitch tension in foreshortened canine diaphragm bundles were not related to sarcoplasmic reticulum. This is consistent with an action of theophylline on the sarcoplasmic reticulum.

Analysis of Variance↗

PubMed1995

Rat diaphragm contractility and histopathology are affected differently by low dose treatment with methylprednisolone and deflazacort.

The extent to which treatment with low doses of the nonfluorinated steroid methylprednisolone affects diaphragm contractility and morphology is unknown. In the present study, we compared the effects of equipotent doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism. Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg.kg-1 or deflazacort 0.5 mg.kg-1 i.m. Contractile properties and histopathology were measured after a 6 week treatment period. During treatment, body weight increased in control and methylprednisolone-treated animals, but decreased by 4.2 +/- 1.1% (mean +/- SD) in the deflazacort group. Similarly, diaphragm mass in the deflazacort group was decreased compared to control and methylprednisolone groups. Twitch tension and twitch characteristics of isolated diaphragm bundles were similar in the three groups. Maximal tetanic tension was decreased in the deflazacort group. The force-frequency curve of the deflazacort bundles shifted downwards compared to control. Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals. Microscopic examination revealed no gross abnormalities in the three groups. Histochemical analysis after staining for myosin adenosine triphosphatase (ATP-ase) showed that in the deflazacort group cross-sectional area of type I, IIa and IIb fibres were decreased. We conclude that low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimensions, while deflazacort at an equipotent dose induced generalized fibre atrophy and changes in diaphragm contractility.

Animals↗

PubMed1994

Contribution of the parasternal intercostals to inspiratory rib elevation in dogs.

To estimate the contribution of the parasternal intercostals to rib elevation during quiet breathing, parasternal intramuscular pressure, Pim, in the fourth interspace and displacement of the rib just below were measured in eight supine anesthetized dogs during: (1) bilateral stimulation of the parasternals, (2) quiet breathing before, after phrenicotomy, and subsequent vagotomy. During quiet breathing, the parasternal contribution averaged 66 +/- 12% of the rib elevation caused by inspiratory rib cage muscles. This contribution decreased in relative terms after phrenicotomy (37 +/- 14%) and subsequent vagotomy (26 +/- 14%) while it tended to increase in absolute terms (from 1.9 +/- 2.4 to 2.1 +/- 2.5 NS, and 2.4 +/- 2.4 mm P < 0.01, respectively). Rib elevation caused by inspiratory rib cage muscles increased after phrenicotomy (116 +/- 63%, P < 0.001) and subsequent vagotomy (279 +/- 60%, P < 0.001) as did Pim (19 +/- 10% NS and 41 +/- 36% P < 0.01, respectively). Moreover, the mechanical interaction of the parasternals among different interspaces measured in three other dogs, was likely to be limited during quiet breathing. We conclude that after diaphragm paralysis, the parasternals played a progressively smaller role while other rib cage muscles were increasingly recruited.

Animals↗

PubMed1994

Inotropic effects of aminophylline on canine diaphragm are enhanced by hyperinflation.

During acute hyperinflation, patients with chronic obstructive pulmonary disease are likely to have foreshortened inspiratory muscles. Because the effects of aminophylline on contractile properties of the foreshortened diaphragm have never been studied in vivo, we compared these effects with those obtained at functional residual capacity (FRC). In 12 anesthetized dogs, bilateral phrenic nerve stimulation (1, 10, 20, and 100 Hz) was performed at FRC and near total lung capacity (TLC) before and 1 h after each injection of aminophylline, given in cumulative doses of 20, 40, and 80 mg/kg (serum levels of 18.7 +/- 6.3, 29.9 +/- 5.9, and 60.4 +/- 11.9 mg/l, respectively). Passive diaphragm shortening from FRC to TLC, measured in eight animals, averaged 30 +/- 12% of the resting length and increased to 35 +/- 12 and 34 +/- 13% after 40 and 80 mg/kg, respectively. After aminophylline, the increase in transdiaphragmatic pressure at FRC did not reach statistical significance, whereas near TLC transdiaphragmatic pressure significantly increased with 80 mg/kg at all stimulus frequencies (e.g., at 20 Hz from 4.4 +/- 2.9 to 6.7 +/- 2.9 cmH2O) and with 40 mg/kg at 10 and 20 Hz. Diaphragm length changes during stimulation were unchanged after aminophylline both at FRC and near TLC. We conclude that aminophylline has a pronounced inotropic effect on foreshortened canine diaphragm, even at concentrations close to the therapeutic range in humans.

Aminophylline↗

PubMed1994

Inotropic effects of theophylline on foreshortened canine diaphragm.

We previously demonstrated that theophylline exerted greater inotropic effects on foreshortened canine diaphragm than on diaphragm placed at resting length in vivo (1). To ensure that these effects result from an effect on the muscle itself, they were examined in vitro. Thus, the effects of increasing doses of theophylline (20, 100, 200, and 400 mg/L) or addition of Krebs solution on twitch tension (Pt) of bundles placed at optimal length (Lo) and 70% Lo were compared. At Lo, compared with time-matched control, Pt significantly increased after theophylline (e.g., 37 +/- 32 versus -8 +/- 12% after 400 mg/L) except with 20 mg/L. At 70% Lo, Pt increased with all theophylline concentrations in a dose-related manner (e.g., 14 +/- 15 versus -6 +/- 7% and 114 +/- 57 versus -8 +/- 11% after 20 and 400 mg/L, respectively). Time to peak tension and half-relaxation time remained unchanged after theophylline both at Lo and 70% Lo. In addition, for a given concentration, twitch potentiation was significantly greater at 70% Lo than at Lo, the difference increasing with increasing concentration (e.g., 3 times greater with 400 mg/L). We conclude that theophylline-induced inotropic effects on Pt were more pronounced on foreshortened canine diaphragm bundles than on bundles placed at Lo. These observations confirm that theophylline-induced inotropic effects on foreshortened muscle previously observed in vivo are likely to result from a direct effect on muscle contractility.

Analysis of Variance↗

PubMed1994

Twitch potentiating effects of theophylline on rat diaphragm are enhanced by foreshortening.

In patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, acute hyperinflation is likely to induce foreshortening of inspiratory muscles. Since no data are available on the effects of inotropic agents at lengths below the optimal length (Lo), we compared the effects of theophylline on forty rat diaphragm bundles placed at Lo and at 70% Lo. Twitches and tetanic stimulations were recorded before and after addition of theophylline, in concentrations of 20, 100, 200 or 400 mg.l-1. Compared with values obtained before theophylline, twitch tension (Pt) and maximal tetanic tension (Po) of the bundles placed at Lo slightly decreased at 20 and 100 mg.l-1 whereas a clear increase in Pt was obtained at 400 mg.l-1 (15 +/- 21% (mean +/- SD)). In contrast, Pt of the bundles placed at 70% Lo increased with all theophylline concentrations, and vastly more than at Lo (e.g. at 400 mg.l-1: 74 +/- 34%, p < 0.05); whereas Po slightly decreased, except at 400 mg.l-1. Moreover, the difference between the effects at Lo and at 70% Lo increased with increasing theophylline concentrations. We conclude that even at low, in vivo attainable serum levels, theophylline exerted greater positive inotropic effects on twitch tension (Pt) of rat diaphragm when foreshortened than when at optimal length.

Animals↗

PubMed1993

Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently.

Diaphragm atrophy and weakness occur after administration of massive doses of corticosteroids for short periods. In the present study the effects of prolonged administration of moderate doses of fluorinated and nonfluorinated steroids were investigated on contractile properties and histopathology of rat diaphragm. 60 rats received saline, 1.0 mg/kg triamcinolone, or 1.25 or 5 mg/kg i.m. prednisolone daily for 4 wk. Respiratory and peripheral muscle mass increased similarly in control and both prednisolone groups, whereas triamcinolone caused severe muscle wasting. Maximal tetanic tension averaged 2.23 +/- 0.54 kg/cm2 (SD) in the control group. An increased number of diaphragmatic bundles in the 5-mg/kg prednisolone group generated maximal tetanic tensions < 2.0 kg/cm2 (P < 0.05). In addition, fatigability during the force-frequency protocol was most pronounced in this group (P < 0.05). In contrast, triamcinolone caused a prolonged half-relaxation time and a leftward shift of the force-frequency curve (P < 0.05). Histological examination of the diaphragm showed a normal pattern in the control and 1.25-mg/kg prednisolone group. Myogenic changes, however, were found in the 5-mg/kg prednisolone group and, more pronounced, in the triamcinolone group. Selective type IIb fiber atrophy was found in the latter group, but not in the prednisolone groups. In conclusion, triamcinolone induced type IIb fiber atrophy, resulting in reduced respiratory muscle strength and a leftward shift of the force-frequency curve. In contrast, 5 mg/kg prednisolone caused alterations in diaphragmatic contractile properties and histological changes without fiber atrophy.

Animals↗