Shape and tension distribution of the active canine diaphragm

2005 ◽  
Vol 288 (4) ◽  
pp. R1021-R1027 ◽  
Author(s):  
Aladin M. Boriek ◽  
Willy Hwang ◽  
Linda Trinh ◽  
Joseph R Rodarte

Both diaphragm shape and tension contribute to transdiaphragmatic pressure, but of the three variables, tension is most difficult to measure. We measured transdiaphragmatic pressure and the global shape of the in vivo canine diaphragm and used principles of mechanics to compute the tension distribution. Our hypotheses were that 1) tension in the active diaphragm is nonuniform with greater tension in the central tendon than in the muscular regions; 2) maximum tension is essentially oriented in the muscle fiber direction, whereas minimum tension is orthogonal to the fiber direction; and 3) during submaximal activation change in the in vivo global shape is small. Metallic markers, each 2 mm in length, were implanted surgically on the peritoneal surface of the diaphragm at 1.5- to 2.0-cm intervals along the muscle bundles at the midline, ventral, middle, and dorsal regions of the left costal diaphragm and along a muscle bundle of the crural diaphragm. Postsurgery, a biplane videofluoroscopic system was used to determine the in vivo three-dimensional coordinates of the markers at end expiration and end inspiration during quiet breathing as well as at end-inspiratory efforts against an occluded airway at lung volumes of functional residual capacity and at one-third maximum inspiratory capacity increments in volume to total lung capacity. A surface was fit to the marker locations using a two-dimensional spline algorithm. Diaphragm surface was modeled as a pressurized membrane, and tension distribution in the active diaphragm was computed using the ANSYS finite element program. We showed that the peak of the diaphragm dome was closer to the ventral surface than to the dorsal surface and that there was a depression or valley in the crural region. In the supine position, during inspiratory efforts, the caudal displacement of the dorsal region of the diaphragm was greater than that of the dome, and the valley along the crural diaphragm was accentuated. In contrast, at lower lung volumes in the prone posture, the caudal displacement of the dome was greater than that of the crural region. At end of inspiration, transdiaphragmatic pressure was ∼6.5 cmH2O, and tensions were nonuniform in the diaphragm. Maximum principal stress σ1 of central tendon was found to be greater than σ1 of the costal region, and that was greater than σ1 of the crural region, with values of 14–34, 14–29, and 4–14 g/cm, respectively. The corresponding data of the minimum principal stress σ2 were 9–18, 3–9, and 0–1.5 g/cm, respectively. Maximum principal tension was approximately parallel to the muscle fibers, whereas minimum tension was essentially orthogonal to the longitudinal direction of the muscle fibers. In the muscular region, σ1 was ∼3-fold σ2, whereas in the central tendon, σ1 was only ∼1.5-fold σ2.

1998 ◽  
Vol 85 (6) ◽  
pp. 2146-2158 ◽  
Author(s):  
Christer Sinderby ◽  
Jennifer Beck ◽  
Jadranka Spahija ◽  
Jan Weinberg ◽  
Alex Grassino

Intersubject comparison of the crural diaphragm electromyogram, as measured by an esophageal electrode, requires a reliable means for normalizing the signal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high and reproducible diaphragm electromyogram root-mean-square (RMS) values and 2) to determine the relative diaphragm activation and mechanical and ventilatory outputs during breathing at rest in healthy subjects ( n = 5), in patients with severe chronic obstructive pulmonary disease (COPD, n = 5), and in restrictive patients with prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher during inspiration to total lung capacity than during sniff inhalation through the nose ( P = 0.035, ANOVA). The RMS (percentage of voluntary maximal RMS) during quiet breathing was 8% in healthy subjects, 43% in COPD patients, and 45% in PPI patients. Despite the large difference in relative RMS ( P = 0.012), there were no differences in mean transdiaphragmatic pressure ( P= 0.977) and tidal volumes ( P = 0.426). We conclude that voluntary maximal RMS is reliably obtained during an inspiration to total lung capacity but a sniff inhalation could be a useful complementary maneuver. Severe COPD and PPI patients breathing at rest are characterized by increased diaphragm activation with no change in diaphragm pressure generation.


1986 ◽  
Vol 60 (1) ◽  
pp. 225-231 ◽  
Author(s):  
A. Oliven ◽  
G. S. Supinski ◽  
S. G. Kelsen

Costal strips of diaphragmatic muscle obtained from animals with elastase-induced emphysema generate maximum tension at significantly shorter muscle fiber lengths than muscle strips from control animals. The present study examined the consequences of alterations in the length-tension relationship assessed in vitro on the pressure generated by the diaphragm in vivo. Transdiaphragmatic pressure (Pdi) and functional residual capacity (FRC) were measured in 22 emphysematous and 22 control hamsters 4–5 mo after intratracheal injection of pancreatic elastase or saline, respectively. In 12 emphysematous and 12 control hamsters Pdi was also measured during spontaneous contractions against an occluded airway. To allow greater control over muscle excitation, Pdi was measured during bilateral tetanic (50 Hz) electrical stimulation of the phrenic nerves in 10 emphysematous and 10 control hamsters. Mean FRC in the emphysematous hamsters was 183% of the value in control hamsters (P less than 0.01). During spontaneous inspiratory efforts against a closed airway the highest Pdi generated at FRC tended to be greater in control than emphysematous hamsters. When control hamsters were inflated to a lung volume approximating the FRC of emphysematous animals, however, peak Pdi was significantly greater in emphysematous animals (70 +/- 6 and 41 +/- 8 cmH2O; P less than 0.05). With electrophrenic stimulation, the Pdi-lung volume curve was shifted toward higher lung volumes in emphysematous hamsters. Pdi at all absolute lung volumes at and above the FRC of emphysematous hamsters was significantly greater in emphysematous compared with control animals. Moreover, Pdi continued to be generated by emphysematous hamsters at levels of lung volume where Pdi of control subjects was zero.(ABSTRACT TRUNCATED AT 250 WORDS)


2001 ◽  
Vol 280 (1) ◽  
pp. R33-R41 ◽  
Author(s):  
Aladin M. Boriek ◽  
Joseph R. Rodarte ◽  
Michael B. Reid

We developed an in vitro preparation to investigate shape and stress distribution in the intact rat diaphragm. Our hypothesis was that the diaphragm is anisotropic with smaller compliance in transverse fiber direction than along fibers, and therefore shape change may be small. After the animals were killed (8 rats), the entire diaphragm was excised and fixed into a mold at the insertions. Oxygenated Krebs-Ringer solution was circulated under the diaphragm and perfused over its surface. A total of 20–23 small markers were sutured on the diaphragm surface. At transdiaphragmatic pressure (Pdi) of 3–15 cmH2O, curvature was smaller in transverse direction than along fibers. Using finite element analysis we computed membrane tension. At Pdi of 15 cmH2O, tension in central tendon was larger than muscle. In costal region maximum principal tension (ς1) is essentially along the fibers and ranged from 6–10 g/cm. Minimum principal tension (ς2) was 0.3–4 g/cm. In central tendon, ς1 was 10–15 g/cm, compared with 4–10 g/cm for ς2. The diaphragm was considerably stiffer in transverse fiber direction than along the fibers.


1998 ◽  
Vol 85 (4) ◽  
pp. 1322-1328 ◽  
Author(s):  
Michael I. Polkey ◽  
Carl-Hugo Hamnegård ◽  
Philip D. Hughes ◽  
Gerrard F. Rafferty ◽  
Malcolm Green ◽  
...  

The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity. The reduction in T2 Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% of vital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responses elicited by low-frequency stimulations; this effect is distinct from and additional to the known length-tension relationship.


1986 ◽  
Vol 60 (1) ◽  
pp. 63-70 ◽  
Author(s):  
J. Road ◽  
S. Newman ◽  
J. P. Derenne ◽  
A. Grassino

Diaphragmatic length was measured by sonomicrometry and transdiaphragmatic pressure (Pdi) by conventional latex balloons in eight dogs anesthetized with pentobarbital sodium under passive conditions and during supramaximal phrenic stimulation. The passive length-pressure relationship indicates that the crural part of the diaphragm is more compliant than the costal part. With supramaximal stimulation the costal diaphragm showed a length-pressure relationship similar in shape to in vitro length-tension curves previously described for the canine diaphragm. The crural part has a smaller pressure-length slope than the costal part in the length range from 80% of optimum muscle length (Lo) to Lo. At supine functional residual capacity (FRC) the resting length (LFRC) of the costal and crural diaphragms are not at Lo. The costal part is distended to 105% of Lo, and crural is shortened to 92% of Lo. Tidal shortening will increase the force output of costal while decreasing that of the crural diaphragm. The major forces setting the passive supine LFRC are the abdominal weight (pressure) and the elastic recoil of the lungs. The equilibrium length (resting length of excised diaphragmatic strips) was 79 +/- 3.6% LFRC for the costal diaphragm and 87 +/- 3.9% LFRC for the crural diaphragm. Similar shortening was obtained in the upright position, indicating passive diaphragmatic stretch at supine LFRC.


1998 ◽  
Vol 85 (3) ◽  
pp. 1123-1134 ◽  
Author(s):  
Jennifer Beck ◽  
Christer Sinderby ◽  
Lars Lindström ◽  
Alex Grassino

The use of esophageal recordings of the diaphragm electromyogram (EMG) signal strength to evaluate diaphragm activation during voluntary contractions in humans has recently been criticized because of a possible artifact created by changes in lung volume. Therefore, the first aim of this study was to evaluate whether there is an artifactual influence of lung volume on the strength of the diaphragm EMG during voluntary contractions. The second aim was to measure the required changes in activation for changes in lung volume at a given tension, i.e., the volume-activation relationship of the diaphragm. Healthy subjects ( n = 6) performed contractions of the diaphragm at different transdiaphragmatic pressure (Pdi) targets (range 20–160 cmH2O) while maintaining chest wall configuration constant at different lung volumes. The diaphragm EMG was recorded with a multiple-array esophageal electrode, with control of signal contamination and electrode positioning. The effects of lung volume on the EMG were studied by comparing the crural diaphragm EMG root mean square (RMS), an index of crural diaphragm activation, with an index of global diaphragm activation obtained by normalizing Pdi to the maximum Pdi at the given muscle length (Pdi/P[Formula: see text]) at the different lung volumes. We observed a direct relationship between RMS and Pdi/P[Formula: see text]independent of diaphragm length. The volume-activation relationship of the diaphragm was equally affected by changes in lung volume as the volume-Pdi relationship (60% change from functional residual capacity to total lung capacity). We conclude that the RMS of the diaphragm EMG is not artifactually influenced by lung volume and can be used as a reliable index of diaphragm activation. The volume-activation relationship can be used to infer changes in the length-tension relationship of the diaphragm at submaximal activation/contraction levels.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Menglong Chen ◽  
Hui Shi ◽  
Shixue Gou ◽  
Xiaomin Wang ◽  
Lei Li ◽  
...  

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.


1986 ◽  
Vol 102 (3) ◽  
pp. 762-768 ◽  
Author(s):  
M Nicolet ◽  
M Pinçon-Raymond ◽  
F Rieger

After denervation in vivo, the frog cutaneus pectoris muscle can be led to degenerate by sectioning the muscle fibers on both sides of the region rich in motor endplate, leaving, 2 wk later, a muscle bridge containing the basal lamina (BL) sheaths of the muscle fibers (28). This preparation still contains various tissue remnants and some acetylcholine receptor-containing membranes. A further mild extraction by Triton X-100, a nonionic detergent, gives a pure BL sheath preparation, devoid of acetylcholine receptors. At the electron microscope level, this latter preparation is essentially composed of the muscle BL with no attached plasmic membrane and cellular component originating from Schwann cells or macrophages. Acetylcholinesterase is still present in high amounts in this BL sheath preparation. In both preparations, five major molecular forms (18, 14, 11, 6, and 3.5 S) can be identified that have either an asymmetric or a globular character. Their relative amount is found to be very similar in the BL and in the motor endplate-rich region of control muscle. Thus, observations show that all acetylcholinesterase forms can be accumulated in frog muscle BL.


2015 ◽  
Vol 123 (4) ◽  
pp. 799-809 ◽  
Author(s):  
Robert Sütterlin ◽  
Antonella LoMauro ◽  
Stefano Gandolfi ◽  
Rita Priori ◽  
Andrea Aliverti ◽  
...  

Abstract Background: Both superimposed high-frequency jet ventilation (SHFJV) and single-frequency (high-frequency) jet ventilation (HFJV) have been used with success for airway surgery, but SHFJV has been found to provide higher lung volumes and better gas exchange than HFJV in unobstructed airways. The authors systematically compared the ventilation efficacy of SHFJV and HFJV at different ventilation frequencies in a model of tracheal obstruction and describe the frequency and obstruction dependence of SHFJV efficacy. Methods: Ten anesthetized animals (weight 25 to 31.5 kg) were alternately ventilated with SHFJV and HFJV at a set of different fHF from 50 to 600 min−1. Obstruction was created by insertion of interchangeable stents with ID 2 to 8 mm into the trachea. Chest wall volume was measured using optoelectronic plethysmography, airway pressures were recorded, and blood gases were analyzed repeatedly. Results: SHFJV provided greater than 1.6 times higher end-expiratory chest wall volume than HFJV, and tidal volume (VT) was always greater than 200 ml with SHFJV. Increase of fHF from 50 to 600 min−1 during HFJV resulted in a more than 30-fold VT decrease from 112 ml (97 to 130 ml) to negligible values and resulted in severe hypoxia and hypercapnia. During SHFJV, stent ID reduction from 8 to 2 mm increased end-expiratory chest wall volume by up to 3 times from approximately 100 to 300 ml and decreased VT by up to 4.2 times from approximately 470 to 110 ml. Oxygenation and ventilation were acceptable for 4 mm ID or more, but hypercapnia occurred with the 2 mm stent. Conclusion: In this in vivo porcine model of variable severe tracheal stenosis, SHFJV effectively increased lung volumes and maintained gas exchange and may be advantageous in severe airway obstruction.


2000 ◽  
Vol 113 (20) ◽  
pp. 3583-3591 ◽  
Author(s):  
M. Fluck ◽  
V. Tunc-Civelek ◽  
M. Chiquet

Tenascin-C and tenascin-Y are two structurally related extracellular matrix glycoproteins that in many tissues show a complementary expression pattern. Tenascin-C and the fibril-associated minor collagen XII are expressed in tissues bearing high tensile stress and are located in normal skeletal muscle, predominantly at the myotendinous junction that links muscle fibers to tendon. In contrast, tenascin-Y is strongly expressed in the endomysium surrounding single myofibers, and in the perimysial sheath around fiber bundles. We previously showed that tenascin-C and collagen XII expression in primary fibroblasts is regulated by changes in tensile stress. Here we have tested the hypothesis that the expression of tenascin-C, tenascin-Y and collagen XII in skeletal muscle connective tissue is differentially modulated by mechanical stress in vivo. Chicken anterior latissimus dorsi muscle (ALD) was mechanically stressed by applying a load to the left wing. Within 36 hours of loading, expression of tenascin-C protein was ectopically induced in the endomysium along the surface of single muscle fibers throughout the ALD, whereas tenascin-Y protein expression was barely affected. Expression of tenascin-C protein stayed elevated after 7 days of loading whereas tenascin-Y protein was reduced. Northern blot analysis revealed that tenascin-C mRNA was induced in ALD within 4 hours of loading while tenascin-Y mRNA was reduced within the same period. In situ hybridization indicated that tenascin-C mRNA induction after 4 hours of loading was uniform throughout the ALD muscle in endomysial fibroblasts. In contrast, the level of tenascin-Y mRNA expression in endomysium appeared reduced within 4 hours of loading. Tenascin-C mRNA and protein induction after 4–10 hours of loading did not correlate with signs of macrophage infiltration. Tenascin-C protein decreased again with removal of the load and nearly disappeared after 5 days. Furthermore, loading was also found to induce expression of collagen XII mRNA and protein, but to a markedly lower level, with slower kinetics and only partial reversibility. The results suggest that mechanical loading directly and reciprocally controls the expression of extracellular matrix proteins of the tenascin family in skeletal muscle.


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