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Biomedical subjects

N Viires

Publications and source records attributed to N Viires.

At least 19 recordsLinked to original sources
PubMed1999

Alteration in diaphragmatic function induced by acute necrotizing pancreatitis in a rodent model.

Some of the common complications of acute necrotizing pancreatitis also involve pulmonary complications. These manifestations are often associated with a cephalad diaphragmatic shift. We hypothized that diaphragmatic function might be directly compromised by the acute abdominal process. This hypothesis was tested on an acute necrotizing pancreatitis (ANP) rat model. We assessed the diaphragm and peripheral (Extensor Digitorum Longus and Soleus) muscle properties in vitro using strips in control (C) and ANP animals. Contractile parameters included single twitch and a force-frequency curve (10 to 100 Hz), and an endurance capacity index (T50%) was calculated after a repetitive stimulation (30 Hz). Breathing pattern was not different between control and ANP animals, and muscular histologic examination was normal. However, ANP was associated with a marked decrease in diaphragmatic strength for all frequencies of stimulation when compared with C. Endurance capacity was also reduced in ANP animals as assessed by a lower T50% (ANP: 31 +/- 10.5 s; C: 49 +/- 10.3 s; p < 0.05). By contrast, no significant change in peripheral muscle function was observed in both groups. We conclude that ANP causes impairment in diaphragmatic strength and endurance capacity, whereas peripheral muscles are spared. These findings suggest that alterations in the respiratory pump may be involved in the genesis of acute respiratory failure in ANP.

Animals↗
PubMed1998

Effects of corticosteroids on epithelial structure and smooth muscle function of rat trachea.

Corticosteroids, efficient drugs for the treatment of severe asthma, may have numerous side effects. We investigated the effects of 7 days of treatment with triamcinolone (1.2 mg x kg(-1) x day(-1)) on the epithelial structure, tracheal smooth muscle cross-sectional area and contractility in the rat. The corticosteroid-injected rats were compared to pair-fed, and pair-weighed animals. Histological studies were performed on transverse sections of glutaraldehyde-fixed tracheal blocks embedded in plastic. In the preparations taken from corticosteroid-injected, pair-fed and pair-weighed animals, pharmacological stimulation with single (10(-3) M) or cumulative (10(-8)-10(-3) M) concentrations of carbachol (in corticosteroid-injected and pair-fed animals), either inside (In) or outside (Out) of the tracheal lumen, was performed and contractions of the tracheal smooth muscle were recorded. We found that triamcinolone administration: 1) reduced the number of epithelial cells and the tracheal smooth muscle cross-sectional area; 2) induced a decrease in maximal tension (Tmax (g); Out: 2.42+/-0.17, 1.03+/-0.1 in pair-fed and corticosteroid-injected, respectively; In: 2.55+/-0.16, 1.1+/-0.16, respectively) without affecting the sensitivity of the tracheal smooth muscle; and 3) reduced the time required to reach 50% Tmax in carbachol (In) preparations. We conclude that the observed changes resulted from atrophy of tracheal smooth muscle induced by undernutrition and atrophy of tracheal smooth muscle and tracheal epithelium induced by corticosteroid treatment.

Animals↗
PubMed1998

Calcium ATPase and respiratory muscle function.

The sarcoplasmic reticulum (SR) of striated muscle is a highly specialized intracellular membrane system that plays a key role in the contraction-relaxation cycle of muscle. Its primary function is the regulation of cytoplasmic Ca2+ concentration. A key element in this regulation is the Sarco(endo)plasmic reticulum Ca2+-adenosine triphosphatase (SERCA), which by sequestering Ca2+ into the SR, induces and maintains relaxation. It has been extensively studied with respect to structure and mechanism of action, and more recently to gene expression. Three separate genes encode five SERCA isoforms, two of which, SERCA 1 and SERCA 2, are expressed in skeletal muscle. In the first part of this review we focus on the general properties of the Ca2+ pump (structure and function and regulation of activity). In the second part we describe variations in SERCA expression in various physiological and pathological situations. These have essentially been studied in the heart and skeletal muscles, with data in respiratory muscles being very limited.

Animals↗
PubMed1994

Effects of mechanical ventilation on diaphragmatic contractile properties in rats.

We measured in rats the effects of 48 h of mechanical ventilation on the weight, contractile properties, and enzymatic profile of the diaphragm, the soleus and the extensor digitorium longus (EDL) muscles. Eighteen animals were randomly divided into a mechanically ventilated (MV, n = 9) group or a control (C, n = 9) group. During the 48 h of mechanical ventilation, animals in the MV group were anesthetized with sodium thiopental and enterally fed with a gastric catheter. Group C animals were neither anesthetized nor mechanically ventilated during the 48-h experimental period, and they had access to food and water ad libitum. Muscular contractile properties were measured in vitro by analysis of force-frequency curves and twitch characteristics. The weights of the three muscles were significantly reduced in the MV group compared with those in the C group. This was accompanied in the diaphragm by a reduction in the normalized force generated for all the frequencies of stimulation, except 20 Hz, whereas twitch characteristics were not modified. The forces generated by the soleus and EDL were not significantly reduced in the MV group compared with those in the C group. Diaphragm, soleus, and EDL citrate synthase and lactate dehydrogenase activities were not significantly different in the two groups. We conclude that mechanical ventilation for 48 h in rats produces a selective force reduction in the diaphragm.

Animals↗
PubMed1992

Effect of steroids on diaphragm of newborn, weanling adolescent, and adult rats.

The purpose of this study was to compare the effects of dexamethasone on the rat diaphragm during the postnatal period and into adulthood. Groups of 48 newborn, 60 weanling adolescent, and 60 adult rats were either (1) treated with DXM (ST, steroid-treated animals) or (2) untreated and pair-fed (C, control animals). After birth, 24 newborn rats were kept with their mother, which received a daily intramuscular injection of 0.5 mg/kg body weight of dexamethasone for 2 wk. Groups of thirty weanling adolescent and 30 adult rats were treated with 1 mg/kg/day of dexamethasone given intramuscularly for 2 wk. Diaphragm performance was compared between ST animals and age-matched C animals. Weights of the body, the diaphragm, the extensor digitorum longus (EDL), and the soleus were obtained. Diaphragm strips were studied in an in vitro preparation to assess contractile and endurance properties. In all the ST animals, body and total diaphragm weights were reduced compared with age-matched C animals (p less than 0.001). In newborn and weanling adolescent ST animals, loss in diaphragm weight was slightly less than in limb muscles, in contrast to adult animals (p less than 0.05). However, diaphragms from adult and weanling adolescent ST animals showed unaffected twitch characteristics, normalized force-frequency curves, and endurance capacity. In the meantime, in newborn ST animals, diaphragm atrophy was associated with significantly decreased force normalized for fiber cross-sectional area and muscle weight (p less than 0.01) and decreased endurance capacity (p less than 0.05). We conclude that the effects of DXM on the diaphragm depend on the developmental status of the muscle at the time of drug administration.

Age Factors↗
PubMed1992

In vitro functions of the rat diaphragm during postnatal development.

This study was designed to determine the developmental changes in the functional characteristics of the rat diaphragm. A total of 150 animals were studied at 1, 3, 5, 7 and 9 weeks of postnatal age. Body and diaphragm muscle weights were measured. Diaphragm strips were studied in an in vitro preparation to assess muscle contractile and endurance properties. Total diaphragm weight increased considerably, by a factor of 23 over the 9 week-period of study and was highly correlated with body weight (r = 0.93, P less than 0.01). However, the ratio of diaphragm-to-body weight decreased progressively with age. In comparison with those from older animals, diaphragms from 1 and 3 weeks old animals: (1) generated similar force normalized for muscle weight but a lower force normalized for fibre cross-sectional area (P less than 0.05), (2) had longer time-to-peak tension and one-half relaxation times (P less than 0.01) and (3) were more resistant to fatigue (P less than 0.01). The mechanisms underlying the diaphragm functional development were discussed.

Age Factors↗
PubMed1991

Multiple effects of BAY K 8644 and nifedipine on isolated diaphragmatic fibers in vitro.

The dose-response effects of BAY K 8644 and nifedipine on diaphragmatic contractility were assessed in vitro. Isolated diaphragmatic fibers were obtained from rats and placed in an open-topped channel of a Plexiglas tissue chamber perfused with continuously flowing Krebs solution heated to 37 degrees C. Isometric twitch force, generated in response to 1-Hz supramaximal electrical stimulation (4 times/min), was measured with a highly sensitive photoelectric force transducer. Low doses of BAY K 8644 or nifedipine (10(-7) M) were without effect on twitch tension. For 10(-6) M, twitch tension increased by 10 +/- 1% (P less than 0.005) for both drugs. For 10(-5) M, twitch tension increased by 12 +/- 1% (P less than 0.05), and maximal contractures were observed (BAY K 8644 and nifedipine). Simultaneous drug administration did not reveal mutual antagonism as expected; instead the effects were additive, with twitch tension increasing by 30 +/- 2% (P less than 0.001) for 10(-5) M BAY K 8644 + nifedipine. Both BAY K 8644 and nifedipine altered twitch characteristics. In low-calcium media (0.5 mM) twitch potentiation produced by the two drugs was further enhanced (increasing 60% for 10(-5) M BAY K 8644 or nifedipine). Contractures, by contrast, were abolished. From these results it is difficult to reconcile a unique action of these drugs on calcium channels as is conventionally accepted.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

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↗
PubMed1990

Expiratory flushing of airways: a method to reduce deadspace ventilation.

A jet of fresh gas entering the trachea during the last part of expiration, expiratory flushing of airways (EFA), may during mechanical ventilation bring the fresh gas interface into the trachea to reduce deadspace. EFA, delivered in a variety of modes, was tested in healthy dogs. EFA allowed tidal volume, peak and mean airway pressure to be reduced by about 25%. EFA was administered in the form of pulses with frequencies 2-8 Hz, and as a continuous flow. The mode was of little importance. EFA was found to be efficient and should be clinically tested.

Animals↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1986

Effect of halothane on diaphragmatic muscle function in pentobarbital-anesthetized dogs.

The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. VE decreased from 8.1 +/- 0.9 to 4.8 +/- 0.4 l . min-1 (P less than 0.001), as FIhal increased from 0 to 0.02. This resulted from a decrease in both mean inspiratory flow (VT/TI) and the duty ratio (TI/TTOT). Transdiaphragmatic pressure (Pdi) and the integrated electrical activity of both hemidiaphragms (Edi) were measured during normal breathing, and during breathing against closed airways (P0di, E0di), in order to obtain an index of the inspiratory neuromuscular output of the diaphragm. With increasing FIhal, there was a significant decrease in Pdi, P0di, Edi, and E0di. The authors measured Pdi and Edi generated during supramaximal stimulation of the two phrenic nerves (PSdi, Esdi) at frequencies of 10, 20, 50, and 100 Hz, in order to eliminate in this decrease the role played by a decrease in the neural drive to breathing. PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.

Anesthesia↗
PubMed1986

Effects of theophylline on isolated diaphragmatic fibers. A model for pharmacologic studies on diaphragmatic contractility.

An in vitro model of isolated diaphragmatic muscle fibers was developed to study the effects of theophylline on diaphragmatic contractility. The effects of theophylline on this model were compared for each dose with the effects of the drugs on a "classic" hemidiaphragmatic muscle preparation. Diaphragmatic strips obtained from 20 rats were placed into an open topped channel of a plexiglass tissue chamber and perfused with continuously flowing Krebs solution heated to 37 degrees and bubbled with a 95% O2 and 5% CO2 gas mixture so as to maintain pH, PO2, PCO2 constant (7.4, 100, and 35 mmHg, respectively). Isometric force generated in response to 1 Hz supramaximal electrical stimulation was measured with a highly sensitive photoelectric transducer. Graded doses of aminophylline (15 to 75 mg/L) were administered and their effect assessed on diaphragmatic peak twitch tension. On the single diaphragmatic muscle fibers preparation, theophylline produced a dose dependent increase in peak twitch tension, which, at a concentration of theophylline of 15 mg/L, a therapeutic dose, amounted to 111 +/- 1.5% of control (p less than 0.05). At a concentration of 60 mg/L the increase in peak twitch tension averaged 35 +/- 2.5% of control, (p less than 0.001). On the other hand, theophylline had no effect on the hemidiaphragm preparation until a dose of 250 mg/L. These findings suggest that the effects of theophylline on diaphragmatic contractility are due to a direct action of the drug on the contractile properties of the diaphragmatic fibers and also validate the presented in vitro model as a promising one for future pharmacologic studies on diaphragmatic contractility.

Animals↗
PubMed1985

Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure.

We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.

Acute Disease↗
PubMed1985

Bilateral phrenic stimulation: a simple technique to assess diaphragmatic fatigue in humans.

Transdiaphragmatic pressure (Pdi) and the rate of relaxation of the diaphragm (tau) were measured at functional residual capacity (FRC) in six normal seated subjects during single-twitch stimulation of both phrenic nerves. The latter were stimulated supramaximally with needle electrodes with square-wave impulses of 0.1-ms duration at 1 Hz before and after diaphragmatic fatigue produced by resistive loaded breathing. Constancy of chest wall configuration was achieved by monitoring the diameter of the abdomen and the rib cage with a respiratory inductive plethysmograph system. During control the peak Pdi generated during the phrenic stimulation amounted to 34.4 +/- 4.2 (SE) cmH2O and represented in each subject a fixed fraction (17%) of its maximal transdiaphragmatic pressure. After diaphragmatic fatigue the peak Pdi decreased by an average of 45%, amounting to 18.1 +/- 2.7 cmH2O 5 min after the fatigue run, and tau increased from 55.2 +/- 9 ms during control to 77 +/- 8 ms 5 min after the fatigue run. The decrease in peak Pdi and the increase in tau observed after the fatigue run persisted throughout the 30 min of the recovery period studied, the peak Pdi amounting to 18.4 +/- 2.8 and 18.9 +/- 3.3 cmH2O and tau to 81.3 +/- 5.7 and 88.7 +/- 10 ms at 15 and 30 min after the end of the fatigue run, respectively. It is concluded that diaphragmatic fatigue can be detected in man by bilateral phrenic stimulation with needle electrodes without any discomfort for the subject and that the decrease in diaphragmatic strength after fatigue is long lasting.

Action Potentials↗
PubMed1985

Effects of hypocalcemia on diaphragmatic strength generation.

We studied the effects of hypocalcemia on diaphragmatic force and diaphragm blood flow (Qdi) in 12 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes surgically implanted in the ventral surface of each hemidiaphragm. The transdiaphragmatic pressure (Pdi) during supramaximal (50 V) 2-s stimulations applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. A catheter was placed via the femoral vein into the left inferior phrenic vein, and Qdi was measured by timed volume collections of left inferior venous effluent. A catheter was introduced in a femoral artery to monitor blood pressure (BP). In five additional dogs, the force generated by the sartorius muscle during electrical stimulation was also studied concomitantly to diaphragmatic force. The animals were mechanically ventilated throughout the experiment, and the arterial blood gases and pH were maintained constant. Hypocalcemia was induced by a continuous infusion of EGTA (70 mg X kg-1 X h-1), which led to a progressive decrease (P less than 0.0001) of ionized calcium plasmatic level from 2.21 +/- 0.4 meq/1 during control to 1.69 +/- 0.06, 1.25 +/- 0.5, and 1.07 +/- 0.5 meq/1 after 30, 60, and 120 min, respectively. Hypocalcemia decreased progressively Pdi, which amounted to 84 +/- 3 (P less than 0.001) and 98 +/- 2% of control values for the low frequencies (10 and 20 Hz) and the high frequencies (50 and 100 Hz), respectively, after 30 min of EGTA infusion and to 74 +/- 5 and 79 +/- 6% for the low and high frequencies, respectively, after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effects and mechanism of action of terbutaline on diaphragmatic contractility and fatigue.

We studied the effects of intravenously administered terbutaline on diaphragmatic force and fatigue during electrical stimulation of the diaphragm in 17 anesthetized dogs. The diaphragm was stimulated indirectly through the phrenic nerves with electrodes placed around the fifth roots and directly with electrodes surgically implanted in the abdominal side of each hemidiaphragm. Transdiaphragmatic pressure (Pdi) during direct or indirect supramaximal 2-s stimulation applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. In seven dogs the administration of terbutaline (0.5 mg) had no effect on Pdi at any stimulation frequency applied directly or indirectly. The effect of terbutaline (0.5 mg) on diaphragmatic fatigue was then tested in 10 other dogs. Diaphragmatic fatigue was produced by continuous 20-Hz electrical supramaxial stimulation of the phrenic nerves during 30 min. At the end of the fatigue procedure Pdi decreased by 50 +/- 5 and 30 +/- 8% of control values at 10 and 100 Hz, respectively, for either direct or indirect stimulation. The decrease in Pdi for low frequencies of stimulation (10 and 20 Hz) lasted 100 +/- 18 min, whereas it lasted only 40 +/- 10 min for the high frequencies (50 and 100 Hz). When terbutaline (0.5 mg) was administered after the fatiguing procedure, Pdi increased within 15 min by 20 +/- 4% at 10 Hz and by 12 +/- 3% at 100 Hz for either direct or indirect stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗