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PubMed1990

Enflurane impairs canine diaphragmatic contractility in vivo.

We examined the effect of enflurane on diaphragmatic contractility in six anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Pdi-stimulus frequency relationship was compared at three levels of anesthesia, namely 1, 1.5, and 2 MAC (minimum alveolar concentration) of enflurane. The sequence of changing anesthetic concentration was randomized between animals. Pdi at 50 and 100 Hz stimulation was significantly decreased with increasing MAC while Pdi at 10 Hz stimulation was not affected by the depth of anesthesia. Pdi of 20 Hz stimulation was significantly decreased at 2 MAC as compared to those at 1 and 1.5 MAC. We conclude that enflurane decreases contractility of the diaphragm mainly through impairment of the neuromuscular transmission and/or membrane excitability. Part of its effects is, however, probably related to the impairment of excitation-contraction coupling, as suggested by the depression of Pdi at 2 MAC in response to 20 Hz stimulation.

Journal Article↗
PubMedDate not supplied

Morphometric analysis of preterm fetal pulmonary development in the sheep model of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) in humans carries high mortality/morbidity attributed to associated pulmonary hypoplasia. An understanding of the effects of CDH on fetal lung growth is important for development of successful treatments. This study aimed to quantitate structural differences between normal and CDH-affected preterm lamb lungs. We hypothesized that (a) pulmonary hypoplasia is present in preterm CDH-affected lungs; (b) the relative degree of pulmonary hypoplasia increases with gestation; and (c) the left upper lobe (LUL) is affected most. Fetal lambs were allocated to two groups. One group underwent surgery (72-74 days gestation) inducing CDH. Both groups (n = 7, n = 7) were delivered by cesarean section at 129 days (term: 145-149). Lungs were obtained at autopsy, were inflation-fixed, processed for histology, and morphometry was performed. Preterm lungs of CDH-affected lambs in comparison to those of normal lambs demonstrated a reduction in the following: lung weight (37.7 g vs. 116.3 g); lung weight:body weight (0.012 vs. 0.040); fixed lung volume (33.6 ml vs. 96.9 ml); gas-exchange surface area (4.56 m(2) vs. 13.70 m(2)); parenchyma:nonparenchyma (59:41 vs. 72:28); and parenchymal airspace:tissue (16:84 vs. 35:65). Non-parenchyma connective tissue was increased (58%), airspaces were more numerous (1077/mm(2)) and smaller (perimeter 76.6 microm), gas-exchange surface density (2394 cm(-1)) was greater and capillary loading (0.04 ml/m(2)) was reduced compared to preterm normal lung (49%; 778/mm(2); 108.7 microm; 2003 cm(-1), 0.11 ml/m(2), respectively). The LUL was affected most. These data quantitate pulmonary hypoplasia in preterm CDH-affected lambs. Comparisons with published data indicate increasing relative hypoplasia as gestation proceeds. Fetal interventions will affect lung development, depending on timing, with intervention still likely to be worthwhile during late gestation.

Animals↗
PubMed1996

[Heart injury following closed thoracic injury].

A 60-year-old man, was admitted in the emergency ward, following a motor vehicle accident. At the time of arrival his clinical state was stable. The initial investigations showed a moderate left haemopneumothorax and fractured ribs. After insertion of a thoracostomy tube into the left pleural cavity he had to undergo surgery for an open fracture of the left arm. Following induction of anaesthesia, a cardiovascular collapse occurred rapidly. An emergency thoracotomy was performed which showed a right ventricular perforation by a rib fragment. The authors discuss the role of possible changes in heart position produced by induction of general anaesthesia. Indeed the decrease in functional residual capacity following induction of anaesthesia with a cephalad diaphragmatic shift may have secondarily exposed the right ventricle to the bevel of a fractured rib.

Arm Injuries↗
PubMed1999

Scanning and transmission electron microscopic study of visceral and parietal peritoneal regions in the rat.

The visceral peritoneum of intraabdominal organs (spleen, stomach, liver, small intestine), omentum majus and the parietal peritoneum of the anterior abdominal wall and the diaphragm were studied in adult Wistar rats by combined scanning and transmission electron microscopy (SEM, TEM). In general, the peritoneal surface consisted of a mesothelium composed of cubic, flat or intermediate cell types delimited by a basal lamina. Cubic mesothelial cells predominated in parenchymal organs (spleen, liver) and were characterized by prominent and indentated nuclei, a cytoplasm richly supplied with organelles, a dense microvillous coat, basal invaginations and elaborate intercellular contacts. Flat mesothelial cells were observed in the intestinal, omental and parietal peritoneum (tendinous diaphragm, abdominal wall) and showed elongated nuclei, scant cytoplasm, a poorly developed organelle apparatus and sparsely distributed microvilli. An intermediate mesothelial cell type was described within the gastric peritoneum characterized by a central cytoplasmic protrusion at the nuclear region containing most of the cytoplasmic organelles and by thin finger-like cytoplasmic processes. The submesothelial connective tissue layer was composed of collagen fiber bundles, fibroblasts and free cells (macrophages, granulocytes, mast cells) and contained blood and lymphatic vessels. In the spleen, elastic fibers formed a membranous structure with intercalated smooth muscle cells. Mesothelial openings were observed as tunnel-like invaginations within the hepatic peritoneum and as clusters of peritoneal stomata within the parietal peritoneum of the anterior abdominal wall and the muscular diaphragm. The round or oval openings of the peritoneal stomata were frequently occluded by overlapping adjacent mesothelial cells and their microvillous coat or obstructed by cellular material. At the side of the peritoneal stomata the mesothelial cell layer was interrupted to allow a direct access to the underlying submesothelial lymphatic system. The mesothelium and lymphatic endothelium shared a common basal lamina. The endothelial cells were discontinuous and displayed valve-like plasmalemmatic interdigitations facilitating an intercellular transport of fluids and corpuscular elements from the peritoneal cavity to the submesothelial lymphatic lacunae. The findings underline the morphological heterogeneity of the peritoneum in visceral and parietal regions, suggesting different functional implications, and further support the presence of extra-diaphragmatic peritoneal stomata.

Abdominal Muscles↗
PubMed1989

Effects of loading and unloading the respiratory system on respiratory control and muscle function.

To determine the effects of internal respiratory loading and unloading on respiratory neuromuscular function, ventilatory (Vi), occlusion pressure (P0.15), transdiaphragmatic pressure (Pdi) and diaphragmatic electromyogram (EMGdi) responses to CO2 rebreathing were assessed in 6 normal volunteers rebreathing gas mixtures denser (63% SF6, 30% O2, 7% CO2) and less dense (63% He, 30% O2, 7% CO2) than air (63% N2, 30% O2, 7% CO2). Loading with SF6 decreased the Vi response to CO2 rebreathing and increased P0.15 and Pdi for a given EMGdi, while the greater the increase in pressure response the less was the decrease in Vi. Unloading with He had the opposite effect. The pattern of breathing was altered with SF6, with Ti and Te increasing and frequency decreasing, while there was no change in timing with He. Internal loading of inspiration and expiration with SF6 elicits compensatory responses that depend on changes of respiratory timing and enhanced diaphragm efficiency. Adjustments to unloading are generally opposite to that observed with loading.

Adult↗
PubMed2003

[Bioenergetic characteristics of the diaphragm after spinal cord injury].

INTRODUCTION: C2 spinal cord hemisection interrupts descending bulbospinal respiratory axons coursing through the cervical spinal cord. One consequence of this type of spinal cord injury is the partial deafferentation of the ipsilateral phrenic nucleus, which renders the hemidiaphragm paralysed. The biochemical properties of the intact or denervated locomotor skeletal muscles have been studied extensively, whereas the biochemical properties of the diaphragm after a cervical spinal cord injury received relatively little attention. This seems unfortunate, given that the diaphragm is the most important mammalian respiratory muscle and is the only skeletal muscle considered essential for survival. Therefore, the purpose of this work was to analyse the bioenergetic characteristics of the diaphragm following a cervical spinal cord injury. METHODS: Segments of the crural diaphragm from rat were homogenised to determine the activities of a glycolytic enzyme, lactate dehydrogenase (LDH), and a Krebs cycle enzyme, citrate synthase (CS). RESULTS: Data show a significant decrease of the CS activity on the ipsilateral hemidiaphragm to the cervical hemisection. No change in the LDH is observed between the animal without or with a cervical spinal cord injury. CONCLUSIONS: These data suggested that the CS activity could be dependent of the nervous influx from the central respiratory rhythm generator and that LDH activity could be maintained by a peripheral respiratory activity or by the cross phrenic phenomenon activation. Biochemical data should be considered in subjects presenting respiratory deficiency induced by a cervical spinal cord injury. Furthermore, the diaphragmatic muscle metabolic activity could be used to evaluate the functional respiratory recovery observed spontaneously or experimentally after using repair strategies of the spinal cord.

Animals↗
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↗
PubMed2004

Reconstruction of the chest wall and the diaphragm using the inverted Y Marlex methylmethacrylate sandwich flap.

OBJECTIVE: Chest wall resection and reconstruction is a demanding operation involving a dedicated team. It can be performed with minimal mortality with excellent cosmetic and functional results using various substitutes. However, reconstructing the lower costal margin with diaphragmatic resection is a challenging prospect needing special techniques. METHODS: We describe a technique of reconstructing the chest wall defect involving the lower costal margin and diaphragm with an Inverted Y Marlex Methylmethacrylate Sandwich Flap. RESULTS: There were no intra operative or postoperative complications and immediate extubation was possible in all six patients without the need for postoperative ventilation. There was a good functional and cosmetic result in all the patients. CONCLUSIONS: This is an easy and safe technique resulting in a stable and satisfactory reconstruction after large antero-lateral full-thickness chest wall resections involving the diaphragm.

Adult↗
PubMed1995

Effect of varying inspired oxygen concentration on diaphragm glutathione metabolism during loaded breathing.

Recent studies have suggested that loaded breathing elicits alterations in diaphragmatic glutathione levels that may be mediated by free radicals and may also be linked to the development of diaphragm fatigue. While free-radical generation in a number of pathophysiologic conditions is known to be a function of ambient oxygen concentrations, the effect of varying inspired oxygen concentration on the diaphragmatic response to loaded breathing (i.e., on diaphragm fatigue and glutathione levels) has not been studied. In this study, we compared the effect of loaded breathing, continued until respiratory arrest in decerebrate rats breathing room air (RA), with the effect of the same load on animals breathing 100% oxygen (O2). After arrest, the animals' diaphragms were excised, force generation was assessed in vitro, and diaphragmatic levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were determined. Similar measurements were made on unloaded control animals. We found both similarities and differences in the response to loading in O2- and RA-breathing animals. O2-breathing loaded animals had a greater load endurance, lower blood pressure at the end of loading, higher carbon dioxide levels, and greater high-frequency fatigue at the conclusion of loaded trials than did RA-breathing animals. The degree of low-frequency fatigue was similar, however, in the O2- and RA-breathing loaded groups (i.e, twitch force averaged 7.9 +/- 0.6, 8.4 +/- 0.5, 3.8 +/- 0.9, and 4.5 +/- 0.8 N/cm2, respectively, in the RA/unloaded, O2/unloaded, RA/loaded, and O2/loaded groups, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Prognostic indicators in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia is associated with significant mortality and morbidity. The aim of this study was to compare a series of tests with respect to prediction of outcome. Tidal volume and compliance of the respiratory system (CRS) were measured preoperatively and on the first and second postoperative days. The maximum and modified ventilation indexes and the maximum Paco2 were noted for the first 6 hours of life and the first 6 hours postoperatively. In addition, it was recorded whether the stomach was within the ipsilateral hemithorax preoperatively. Twenty infants were studied (median gestational age, 38 weeks; range, 31 to 40), six of whom had a poor outcome, ie, they died or remained oxygen-dependent after 28 days. A CRS of less than 0.18 mL/cm H2O/kg was the most accurate predictor of poor outcome, with 66% sensitivity and 100% specificity. The authors conclude that lung function measurement are useful in the assessment of infants with congenital diaphragmatic hernia.

Carbon Dioxide↗
PubMed1987

[Action of aminophylline on the strength of contraction of the diaphragm in patients with chronic obstructive respiratory insufficiency].

The effect of a sustained-release aminophylline preparation on diaphragmatic contractility was investigated in patients with stable chronic obstructive lung disease (FEV1 = 22.6% of predicted value). Ten such patients were tested before (control) and after a week's course of oral aminophylline. Diaphragmatic contractility was evaluated by measuring the transdiaphragmatic pressure generated at residual functional capacity by bilateral electrical stimulation of the phrenic nerves. The nerves were stimulated supramaximally at 1 Hz, using needle electrodes. Plasma aminophylline levels (12.5 +/- 0.9 mg/l) were within therapeutic range in all patients. After treatment with aminophylline, for each stimulation the transdiaphragmatic pressure increased significantly from 14 +/- 1.3 to 17 +/- 1.3 cm H2O (+21%; P less than 0.005). These results confirm that aminophylline increases the force of contraction of the diaphragmatic fibres electively tested by the technique used. Long-term treatment with theophylline in therapeutic doses may be of interest in such patients, as it might improve their diaphragmatic contractility and result in better control of both respiratory muscle fatigue and episodes of acute respiratory failure.

Aged↗
PubMedDate not supplied

Heart hypoplasia in an animal model of congenital diaphragmatic hernia.

PURPOSE: In previous papers, we described a new experimental model of congenital diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic strategies for prevention of the functional and structural immaturity of the lungs associated with this defect. In addition to lung hypoplasia, pulmonary hypertension, biochemical, and structural immaturity of the lungs, the hemodynamics of infants and animals with congenital diaphragmatic hernia are markedly altered. Hence, cardiac hypoplasia has been implicated as a possible cause of death in patients with congenital diaphragmatic hernia, and it is hypothesized to be a probable consequence of fetal mediastinal compression by the herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat models of congenital diaphragmatic hernia. The purpose of the present experiment was to verify the occurrence of heart hypoplasia in our new model of surgically produced congenital diaphragmatic hernia in fetal rabbits. METHODS: Twelve pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 (normal full gestational time - 31 to 32 days) to create left-sided diaphragmatic hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again underwent surgery, and the delivered fetuses were weighed and divided into 2 groups: control (non-surgically treated fetuses) (n = 12) and congenital diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted for histologic and histomorphometric studies. RESULTS: During necropsy, it was noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the liver herniated throughout the surgically created defect and occupied the left side of the thorax, with the deviation of the heart to the right side, compressing the left lung; consequently, this lung was smaller than the right one. The body weights of the animals were not altered by congenital diaphragmatic hernia, but heart weights were decreased in comparison to control fetuses. The histomorphometric analysis demonstrated that congenital diaphragmatic hernia promoted a significant decrease in the ventricular wall thickness and an increase in the interventricular septum thickness. CONCLUSION: Heart hypoplasia occurs in a rabbit experimental model of congenital diaphragmatic hernia. This model may be utilized for investigations in therapeutic strategies that aim towards the prevention or the treatment of heart hypoplasia caused by congenital diaphragmatic hernia.

Animals↗
PubMed1986

Effects of digoxin on diaphragmatic strength generation.

Contrary to hindlimb muscle, extracellular calcium plays an important role in diaphragmatic strength generation (J. Appl. Physiol. 58: 2054-61, 1985). Since the inotropic effect of digitalis appears to be related to cell membrane transport of calcium, we studied the effect of digoxin on diaphragmatic contractility in 20 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes. 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 at functional residual capacity. Cardiac output was measured with a Swan-Ganz catheter and diaphragmatic blood flow (Qdi) by timed volume collections of left inferior venous effluent. The force generated by the sartorius muscle during electrical stimulations was studied concomitantly to Pdi. In 10 dogs (group A) 0.04 mg/kg of digoxin was infused in 10 min. In 10 other dogs (group B) 0.2 mg/kg was administered. All measurements were performed during control and 30, 60, 90, and 120 min after digoxin administration. In group A, digoxin plasmatic level at 60 min reached a therapeutic range in all dogs (1.8 +/- 0.3 ng/ml), whereas in group B, digoxin plasmatic level was higher (8 +/- 1.3 ng/ml). No significant change in cardiac output and Qdi was noted after administration of digoxin, either in the dogs of group A or those of group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Effects of carotid body excision on recovery of respiratory function in C2 hemisected adult rats.

In a previous study, we described the spontaneous recovery of respiratory motor function in adult rats subjected to a left C2 hemisection 6-16 weeks post-injury without any therapeutic intervention. We extend the previous findings by demonstrating in the present study that rats subjected to a left C2 hemisection with bilateral carotid body excision will also recover respiratory-related activity in the paralyzed ipsilateral hemidiaphragm. However, in this instance, recovery is significantly accelerated; i.e., it is evident as early as 2 weeks after spinal cord injury. Two experimental groups (and noninjured and sham-operated controls) of rats were employed in the study. H-CBE animals were subjected to a left C2 hemisection plus bilateral carotid body excision while H-CBI animals were subjected to a left C2 hemisection only. Carotid body excision was confirmed by the sodium cyanide test. The animals were allowed to survive for 2 weeks after hemisection. Thereafter, electrophysiologic assessment of respiratory activity was conducted in all animals. Spontaneous recovery of respiratory-related activity in the paralyzed hemidiaphragm (indicated by left phrenic nerve activity) was detected in all H-CBE animals while H-CBI animals did not express spontaneous recovery of diaphragmatic activity. The magnitude of recovered activity when expressed as a function of contralateral phrenic nerve activity was 48.8 +/- 3.8%. When expressed as a function of the homolateral phrenic nerve in noninjured animals, the magnitude amounted to 25.6 +/- 2.8%. Although the mechanisms responsible for the apparent early onset of spontaneous recovery are unknown, it is likely that a reorganization of the respiratory circuitry in the CNS may be involved. The significance of the findings is that it may be feasible to modulate the onset of functional recovery following cervical spinal cord injury by specifically targeting peripheral chemoreceptors.

Analysis of Variance↗
PubMed1991

On the anisotropy of the canine diaphragmatic central tendon.

We studied the mechanical and anatomical anisotropy of the canine diaphragmatic central tendon (CT). Dumb-bell-shaped strips with effective dimensions of 10 x 2 mm (length x width) were cut from different regions of the canine diaphragmatic CT in two different orientations relative to the direction of neighboring muscle fibers. Specimens sampled with their long axial dimension oriented parallel to the neighboring muscle fibers were named Group-1 and those sampled with an orientation perpendicular to the neighboring muscle fibers were named Group-2. Results from one-dimensional stress-strain and tensile failure strength tests revealed that the CT is a nonlinear, inelastic, and anisotropic material. Group-1 specimens were found to have a higher stiffness, higher failure strength and higher strain energy density at failure than Group-2 specimens. Polarized microscopy showed that multiple sheets of collagen fiber bundles formed an orthogonal network in the tendon. Collagen fiber bundles along Group-1 direction formed parallel trajectory lines connecting the neighboring costal and crural muscles; bundles along Group-2 direction were observed to orient 90 degrees away. At the central apex region of the CT, collagen bundles of Group-1 formed a fan-like trajectory pattern. This collagen network architecture was compared favorably to the trajectories of an approximated principal stress field in the CT due to simulated contractile forces from its adjacent costal and crural muscles. These combined results suggest a structure-function relationship for the anatomical and mechanical anisotropy in the canine diaphragmatic CT.

Animals↗
PubMed1983

Diaphragm in emphysematous hamsters: sarcomere adaptability.

We investigated whether the shift in the diaphragmatic length-tension curve of emphysematous animals was due to changes in either sarcomere number or sarcomere length. In vitro length-tension characteristics of the diaphragm were evaluated in control and emphysematous hamsters. Emphysema was induced by a single endotracheal instillation of elastase. Functional residual capacity, measured by means of a plethysmograph, was about twice that measured in emphysematous animals compared with control animals. Small diaphragmatic bundles were isolated and evaluated for their length-tension characteristics. The length-tension curve of diaphragms from emphysematous animals was displaced toward the left. Maximal tetanic tensions were similar in both groups, whereas optimal bundle length was significantly decreased in the emphysematous animals. Sarcomere number and sarcomere length at optimal length were then calculated for the diaphragmatic bundles. The bundles from emphysematous animals were found to have a significantly reduced number of sarcomeres, as well as a significantly decreased sarcomere length at optimal compared with control values. The total number of sarcomeres were also found to be significantly negatively correlated with the animal's functional residual capacity. From these results, we conclude that the decrease in diaphragmatic length, seen with hyperinflation, is due mainly to a loss of sarcomeres and possibly to a small decrease in sarcomere length measured at optimal bundle length.

Adaptation, Physiological↗