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G Gayan-Ramirez

Publications and source records attributed to G Gayan-Ramirez.

33 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Respiratory function of the rib cage muscles.

Elevation of the ribs and expansion of the rib cage result from the co-ordinated action of the rib cage muscles. We wished to review the action and interaction of the rib cage muscles during ventilation. The parasternal intercostal muscles appear to play a predominant role during quiet breathing, both in humans and in anaesthetized dogs. In humans, the parasternal intercostals act in concert with the scalene muscles to expand the upper rib cage, and/or to prevent it from being drawn inward by the action of the diaphragm. The external intercostal muscles are considered to be active mainly during inspiration, and the internal intercostal muscles during expiration. The respiratory activity of the external intercostals is minimal during quiet breathing both in man and in dogs, but increases with increasing ventilation. Inspiratory activity in the external intercostals can be enhanced in anaesthetized animals and humans by inspiratory mechanical loading and by CO2 stimulation, suggesting that the external intercostals may constitute a reserve system, that may be recruited when the desired expansion of the rib cage is increased. The triangularis sterni is an important expiratory muscle during quiet breathing in animals, but it is not active during quiet breathing in man. However, during expiration below functional residual capacity (FRC), and during speech, laughing and coughing, the triangularis sterni is recruited and plays an increasingly important role.

Biomechanical Phenomena↗

Quantitative EEG changes under various conditions of hyperventilation in the sensorimotor cortex of the anaesthetized cat.

The effects on the EEG rhythms recorded from the sensorimotor cortex (post-sigmoid gyrus) of anaesthetized cats were studied under 4 conditions of artificial mechanical hyperventilation (HV) before and after cervical bilateral vagotomy. In animals with intact vagus nerves, using visual examination, EEG changes were only observed within the 2nd min during HV produced by increased stroke volume (delta V) with associated hypocapnia. Quantitative EEG (qEEG) showed that, for the same increase in minute ventilation and the same degree of hypocapnia, delta V induced a greater and earlier relative decrease (2nd min) in the power density of delta, theta and alpha bands, than increased pump frequency (delta F). The delta F tests produced a fall only in the theta band and within the 3rd min. With constant paCO2, transient modifications occurred only with delta V and were limited to the first 30 sec. In bivagotomized cats, moderate EEG responses to delta V plus associated hypocapnia persisted partly in the alpha band. Finally, no changes appeared with delta V or delta F when the vagus nerves were cut and paCO2 was maintained constant. The present data suggest strongly that, in anaesthetized cats, peripheral vagal afferents from the respiratory system play a major role in the EEG changes caused by artificial hyperventilation.

Animals↗

Pulmonary vagal sensory afferents and spontaneous EEG rhythms in the cat sensorimotor cortex.

Interactions between vagal afferent fibres and spontaneous electroencephalographic (EEG) activity, recorded on the sensorimotor cortex of the cat, were studied during the mechanical activation of pulmonary afferents. The interactions were compared to the cortical effects of the electrical stimulation of all vagal fibers or to the chemical activation of unmyelinated vagal afferents (C-fibers) by phenyldiguanide. The present study was performed on anesthetized cats, artificially ventilated with open chest. Over 60 locations were explored on the posterior sigmoid gyrus. Repetitive electrical stimulation (30 Hz, 0.8 ms shock duration) of the contralateral cervical vagus nerve or of both nerves induced within less than 5 s changes in the pattern and periodicity of EEG spindles, associated with depressed background rhythms or rhythmic EEG activities. Cortical responses were also observed after i.v. injection of phenyldiguanide. Changes in activity of pulmonary stretch receptors by lung hyperinflation or suppression of phasic lung inflations ('stop pump') had no effect on the EEG rhythms. On the other hand, expiratory threshold loading or passive hyperdeflation of the lungs elicited EEG changes similar to those obtained by electrical stimulation of all vagal fibers. After bilateral vagotomy, all these responses disappeared or were delayed. The present observations strongly suggest that sensory information carried by thin vagal fibers greatly influences cortical rhythms in the cat sensorimotor cortex.

Animals↗