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Biomedical subjects

M Aubier

Publications and source records attributed to M Aubier.

At least 145 records · Page 8Linked to original sources

A preparation for in vivo study of the diaphragmatic microcirculation in the rat.

A new preparation is described for the study of the microcirculation of the rat diaphragm by in vivo microscopy. After midline laparotomy, the abdominal site of the diaphragm muscle was exposed. The rat was mechanically ventilated and placed in the Trendelenburg position, thus allowing a microscope placed on a three-dimensional articulated system to be set up perpendicular to the diaphragm. The diaphragm was then transilluminated by inserting fiberoptic microprobes into the thorax cavity by thoracotomy in the fifth intercostal space. This preparation allowed us to describe the morphological characteristics of the arteriolar network in vivo. As regards the venular network, two parts were distinguished: one part collects the blood of the external half of the diaphragm, runs roughly parallel to the arterioles, and converges toward the internal mammary and intercostal veins; the other part collects the blood of the central half of the diaphragm and converges on the central venous arcade along its central tendon. Anastomotic channels between these two parts were observed, as well as spontaneous inversion of the direction of the blood flow, indicating the presence of unsteady pressure gradients in some branches of the venular network. Capillary density was also studied by measuring intercapillary distance, whose mean value was 21.43 +/- 0.67 microns. No differences in intercapillary distance were found between the external and central parts of the diaphragm. In conclusion, we describe a preparation which allowed us to study the diaphragmatic microcirculation for at least 2 hr under good hemodynamic conditions. The study of this specific microcirculation is important because the diaphragm's metabolism and functions are specific and because it is essential to life that its perfusion should be adapted to its specific metabolic requirements.

Animals↗

Preventive effects of indomethacin on diaphragmatic contractile alterations in endotoxemic rats.

We evaluated the effects of a sublethal Escherichia coli endotoxemia with and without concomitant administration of indomethacin on diaphragmatic strength in an in vivo rat model. Ninety-six rats were inoculated subcutaneously on two successive days with 0.3 and 0.6 mg/100 g body weight of E. coli lipopolysaccharide, respectively (E animals, n = 64), or saline (C group, n = 32). E animals were divided into two groups based on subcutaneous administration of endotoxin alone (E group, n = 32) or endotoxin plus indomethacin (2.5 mg/kg body weight/day) (EI group, n = 32). Diaphragmatic strength was evaluated in 14 animals from each group 2 days after the first endotoxin or saline administration. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure (Pdi) during electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 100 Hz). Lung histologic examination and measurements of lung weights were performed 1 and 2 days after the first endotoxin or saline administration in nine animals of each group each day. A slight increase in the number of neutrophils without alveolar septal thickening and alveolar edema was observed in the lungs of endotoxin-inoculated animals. No differences in the lung weight to body weight ratio nor in the dry to wet weight ratio of the lungs were noted between C, E, and EI groups. Diaphragmatic weight was not different in the three groups, whereas the weights of the extensor digitorum longus, tibialis anterior, and soleus muscles were significantly reduced in E compared with C and EI animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of steroids on diaphragmatic function in rats.

The present study was undertaken to determine the effects of 8 days of corticosteroid administration on diaphragmatic atrophy and contractile properties. One hundred sixty rats were divided into a pair-fed (PF) group (n = 80) and a steroid-treated (ST) group (n = 80). The treated rats received a single injection of Kenacort 80 retard (0.1 mg/kg intramuscularly). The experimental period was 8 days. Steroid treatment resulted in a 30% decrease in body weight in the ST group when compared with the PF group. Diaphragmatic mass in the ST group decreased in proportion to body weight (30%) as did the weight of the extensor digitorum longus (EDL). The soleus muscle was unaffected. The diaphragmatic atrophy was associated with a significant decrease (p less than 0.001) in normalized tetanic force as assessed both in vivo and in vitro. Diaphragmatic strength was determined in vivo by measuring transdiaphragmatic pressure (Pdi) during bilateral electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 1000 Hz). The force-frequency relationship was also studied in vitro using direct stimulation of costal diaphragmatic strips. In both preparations, twitch and low-frequency force were unaffected, whereas normalized tetanic force in the ST group was markedly reduced compared with that in the PF group (p less than 0.001). Soleus and EDL muscles were also studied in vitro. Although steroid treatment had no effect on the soleus, in the EDL, a slight (11%) decrease in normalized tetanic tension was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The respiratory response to CO2 and O2 in patients with coma due to voluntary intoxication with barbiturates and carbamates.

We have investigated the respiratory response to CO2 and to O2 in comatose subjects self intoxicated with barbiturates and carbamates. The chemical drive of 12 such patients with coma was compared with that of comparable normal subjects. The ventilatory response to CO2 was depressed but the P0.1 response was of the same order of magnitude as in normals. O2 had little effect on the ventilatory parameters and occlusion pressure. There was no difference between the two groups of patients, indicating that the respiratory changes observed were more dependent on the intensity of the intoxication than on the nature of the drugs. In addition, mechanical factors seem mainly responsible for the depressed ventilatory response to CO2.

Adult↗

Pharmacological treatment of respiratory insufficiency.

The respiratory muscles, as any other skeletal muscle can fatigue. Respiratory muscle fatigue has been shown to play an important role in the pathogenesis of dyspnea and respiratory failure. Treatment of this respiratory muscle dysfunction appears therefore to be clinically important in patients with respiratory diseases. The respiratory muscles and particularly the diaphragm present some particularities among the skeletal muscles. The diaphragm excitation-contraction coupling processes and blood flow appear to be closer to the myocardium than to the peripheral skeletal muscles. Pharmacological agents that enhance respiratory muscle function by acting at these two levels may therefore be clinically useful. This review deals essentially with respiratory muscle dysfunction and its pharmacological approach.

Animals↗

The transition between apnoea and spontaneous ventilation in patients with coma due to voluntary intoxication with barbiturates and carbamates.

We have investigated the transition from apnoea to spontaneous breathing in five comatose patients self intoxicated with barbiturates and carbamates. All patients were apnoeic on admission, and were studied throughout the course of recovery. The transition between the first respiratory movements and a stable and nearly normal ventilation (stable respiratory activity) ranged from 15 to 105 min, a very short time compared to the duration of the apnoeic state that lasted 6 to 72 h from admission. Minute ventilation and occlusion pressure during the first respiratory movements were 6.3 +/- 2.7 l.min-1 and 1.35 +/- 0.45 kPa, respectively. These values increased by roughly 50 and 100% by the time stable respiratory activity was achieved. The increase in minute ventilation was entirely due to an increased inspiratory flow, in relation to a proportionate increase in occlusion pressure, and without significant changes in the respiratory times or in the effective elastance. We conclude that the transition between apnoea and stable respiratory activity is characterized by its rapidity, by the fact that respiratory times are fixed throughout the recovery process, and by the fact that effective elastance is high.

Adult↗

A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease.

To assess the effects of theophylline in chronic obstructive pulmonary disease, we conducted a randomized, placebo-controlled, double-blind, crossover trial in 60 patients with severe but stable disease. The patients (mean age, 61 years) were studied before and after two months of placebo and two months of treatment with a sustained-release preparation of theophylline (10 mg per kilogram of body weight per day), administered orally. The two treatments were administered in a random order and separated by an eight-day washout period. After taking theophylline for two months (mean plasma concentration, 14.8 mg per liter), as compared with the two months of placebo, the patients had significant improvements in dyspnea, pulmonary gas exchange (partial pressure of arterial oxygen, 66 vs. 61 mm Hg [P less than 0.0001]; partial pressure of arterial carbon dioxide, 44 vs. 49 mm Hg [P less than 0.0001]), vital capacity (63 percent vs. 58 percent of the predicted value [P less than 0.0001]), and forced expiratory volume in one second (36 percent vs. 32 percent of the predicted value [P less than 0.0001]), with no significant change in airway resistance or functional residual capacity. Minute ventilation increased by a mean of 18 percent (P less than 0.0001) in the patients taking theophylline because of increased tidal volume, with no change in respiratory frequency. The respiratory-muscle performance of the patients taking theophylline improved by approximately 29 percent (P less than 0.0001), as indicated by a decline in the ratio of inspiratory pleural pressure during quiet breathing to maximal pleural pressure. We conclude that theophylline improves respiratory function and dyspnea in patients with severe chronic obstructive pulmonary disease and that these improvements are probably due to better respiratory-muscle performance.

Bronchitis↗

Dopamine effects on diaphragmatic strength during acute respiratory failure in chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To assess the effects of dopamine, which has an inotropic effect on the myocardium and increases renal and splanchnic blood flow, on diaphragmatic contraction. DESIGN AND PATIENTS: We studied the changes in transdiaphragmatic pressure during electrical bilateral supramaximal stimulation of the phrenic nerves in eight patients with chronic obstructive pulmonary disease during acute respiratory failure. In three patients, changes in diaphragmatic blood flow were also evaluated. METHODS: All patients were intubated and artificially ventilated. Stimulated transdiaphragmatic pressure, cardiac output, evaluated with a Swan Ganz catheter, and diaphragmatic blood flow, evaluated by timed volume collections of left phrenic venous effluent (a catheter was introduced into the right femoral vein and advanced into the left inferior phrenic vein) were measured before dopamine infusion, every 10 minutes after the onset of dopamine infusion (10 micrograms/kg body weight.min during 30 minutes) and 15 minutes after the end of dopamine infusion. Arterial blood gases and pH were measured before and at the end of dopamine infusion. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and pH were maintained within normal range by mechanical ventilation throughout the study. With dopamine infusion, heart rate increased by 17% (P less than 0.001) and cardiac output by 40% (P less than 0.001) on the average. The increase in cardiac output was accompanied by a marked increase in diaphragmatic blood flow (30% on the average) in the three patients in whom it was measured (P less than 0.001). Diaphragmatic strength also increased significantly during dopamine administration. Transdiaphragmatic pressure for an identical phrenic stimulation increased by 30% (P less than 0.001) on the average. The changes in cardiac output, diaphragmatic blood flow, and transdiaphragmatic pressure persisted throughout the infusion period; all values returned to control values 15 minutes after the end of dopamine administration. CONCLUSIONS: Dopamine has a potent effect on diaphragmatic strength generation and diaphragmatic blood flow in patients with chronic obstructive pulmonary disease during acute respiratory failure. It is possible to improve diaphragmatic contraction in these patients by administering pharmacologic agents that augment diaphragmatic blood flow.

Action Potentials↗

Respiratory muscle fatigue.

When respiratory muscle demands for energy exceed supplies, the energy stored within the muscles is depleted and the force of contraction diminishes. This state is called inspiratory muscle fatigue. When it occurs alveolar ventilation decreases, arterial carbon dioxide tension (PaCO2) increases and hypercapnic respiratory failure ensues. It has also been suggested that such a dysfunction of the respiratory muscles contributes to the pathogenesis of acute respiratory failure. The purpose of this article is to review those factors that predispose to respiratory muscle fatigue and determine energy demand and supply and the principal means of investigation available to detect respiratory muscle fatigue in the clinical setting.

Energy Metabolism↗

Acute diaphragmatic changes induced by starvation in rats.

The aim of this study was to assess in an in vivo rat model the effects of total starvation for 4 d on diaphragmatic strength and endurance. Twenty-four rats were divided equally into a control (CTL) group and a starved (ST) group. Diaphragmatic strength was assessed and endurance index was calculated. Starvation induced a parallel decrease in body weight and diaphragmatic weight amounting to 18% of the control group. Diaphragmatic contractility was impaired in the ST group. This reduction was associated with a significant reduction in transdiaphragmatic pressure (Pdi) for all the frequencies of stimulation, except 20 Hz, in the ST animals as compared with the CTL animals; however, no significant difference in Pdi expressed per gram of diaphragmatic mass was observed. Endurance index was 0.63 +/- 0.01 1.4 +/- 0.02 in the ST and CTL animals (p less than 0.01), respectively. We conclude that a 4-d total fast produces a reduction in diaphragmatic weight, which is associated with a decreased diaphragmatic strength and reduced endurance capacity.

Animals↗

Effects of isoflurane on contractile properties of diaphragm.

Isoflurane has been shown to depress skeletal muscle force in vitro, but data are not available regarding the effects of isoflurane on diaphragmatic muscle function in vivo. To answer this question, 15 rats anesthetized with pentobarbital and mechanically ventilated were studied. They were divided into three groups of five animals each, according to the administered concentration of isoflurane. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 0.5 Hz, 20 Hz, 50 Hz, and 100 Hz under quasi-isometric conditions. After a control measurement (C), isoflurane was administered at a constant concentration (0.5, 1, or 1.5 MAC) and Pdi measurements were repeated after 30 min of isoflurane exposure (T1) and 30 min after discontinuing isoflurane (T2). In the group breathing 1.5 MAC isoflurane, the time constant of diaphragmatic relaxation (tau) and integrated electrical activity of the diaphragm (Edi) were also assessed. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three isoflurane concentrations. A significant increase in Pdi at 20 Hz was observed at T1, which returned to control after 30 min recovery (T2). No change in Pdi during 50 Hz stimulation was noted during 0.5 and 1 MAC isoflurane exposure, whereas it was reduced at T1 during 1.5 MAC. For 100 Hz stimulation, a significant decrease in Pdi was noted for all groups at T1, which returned toward control values at T2. Edi was markedly reduced for 50 and 100 Hz stimulation, but this reduction was also transient, since Edi returned toward control values at T2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epithelial vs. serosal stimulation of tracheal muscle: role of epithelium.

There is evidence implying an active role of airway epithelium in the modulation of bronchomotor tone. To study this phenomenon, we designed an in vitro system allowing pharmacological stimulation of either the inside or outside of the airway lumen. Rat tracheas were excised, cannulated, and their inside and outside perfused independently with Krebs solution. Two hooks were inserted through opposite sides of the tracheal wall, the lower one was attached to a fixed point, while the upper one was connected to a force transducer. Isometric contractions of the tracheal muscle were elicited by carbachol solution perfused in single and cumulative concentrations. In one-half of the preparations the epithelium was mechanically removed. Stimulation of the inside or outside of the trachea produced equal maximal tracheal muscle tension [1.55 +/- 0.14 and 1.2 +/- 0.09 (SE) g in and out, respectively]. The time course of tension development was longer when carbachol was administered inside the trachea: an effect that was abolished when the epithelium was removed. In addition, removal of the epithelium was found 1) to increase the maximal tension irrespective of the route of carbachol perfusion and 2) to increase the sensitivity of the preparation to carbachol stimulation.

Animals↗