Contractile properties of intercostal muscles and their functional significance

To have some insight into the functional coupling between the parasternal intercostals (PS) and the diaphragm (DPM), we have examined the isometric contractile properties of bundles from canine PS and DPM muscles. Bundles of external (EXT) and internal (INT) interosseous intercostals were studied for comparison. In addition we have related sonometrically measured length of the intercostals in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We found that 1) intercostal twitch speed is significantly faster than DPM, thus displacing their relative force-frequency curve to the right of that of the DPM; 2) the ascending limb of the active length-tension curve of all intercostals lies below the DPM curve; i.e., at 85% Lo, PS force is 46% of maximal force (Po), whereas DPM force is still 87% Po; 3) for any given length change beyond Lo, all intercostals generate greater passive tension than the DPM; 4) Po is greater for the intercostals than the DPM; and 5) at supine FRC, both EXT and INT in dogs are nearly operating at Lo, whereas the PS are operating at a length greater than Lo. We conclude that 1) PS produce less force than DPM during breathing efforts involving low- (10–20 Hz) stimulation frequencies, but they generate more force than DPM when high- (greater than 50 Hz) stimulation frequencies are required; and 2) the pressure-generating ability of the PS is better preserved than that of the DPM with increases in lung volume.

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In vivo contractile properties of fatigued diaphragm

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.2.471 ◽

1987 ◽

Vol 63 (2) ◽

pp. 471-478 ◽

Cited By ~ 13

Author(s):

J. Road ◽

R. Vahi ◽

P. del Rio ◽

A. Grassino

Keyword(s):

Spontaneous Breathing ◽

Central Fatigue ◽

Contractile Properties ◽

Peripheral Fatigue ◽

Electromyographic Activity ◽

Force Frequency ◽

Shortening Velocity ◽

Velocity Of Shortening ◽

The Right

The effects of fatigue on diaphragmatic contractility in vivo are unknown. In this study we used sonomicrometry to examine the velocity of shortening and lengthening and the amount of shortening in the fresh and fatigued canine hemidiaphragm (8 dogs) including the force generated. Fatigue was produced by epiphrenic stimulation of the left phrenic nerve; the right hemidiaphragm acted as the control. We found that 1) hemidiaphragmatic fatigue caused an increase in frequency with reduced tidal volume; 2) fatigue resulted in a near complete cessation of tidal shortening during spontaneous breathing; 3) there was an initial decrease in central activation (electromyogram) to the fatigued hemidiaphragm, an indication of central fatigue; 4) force-frequency curves showed a considerable and prolonged loss of the amount of shortening, velocity, and force generated by the fatigued hemidiaphragm during supramaximal stimulation, an indication of peripheral fatigue; and 5) during spontaneous breathing in the fatigued hemidiaphragm, tidal shortening remained reduced for up to 3 h, whereas in the right right hemidiaphragm tidal shortening and electromyographic activity did not change. We conclude that fatigue of a hemidiaphragm alters the spontaneous breathing pattern and produces profound modifications in its contractile properties without altering contralateral hemidiaphragmatic performance.

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Adaptability of the hamster diaphragm to exercise and/or emphysema

Journal of Applied Physiology ◽

10.1152/jappl.1982.53.5.1263 ◽

1982 ◽

Vol 53 (5) ◽

pp. 1263-1272 ◽

Cited By ~ 69

Author(s):

G. A. Farkas ◽

C. Roussos

Keyword(s):

Contractile Properties ◽

Force Frequency ◽

Control Groups ◽

Optimal Length ◽

Time To Peak ◽

Residual Capacity ◽

Vitro Analysis ◽

Tetanic Tension ◽

In Vitro Analysis

In vitro contractile properties of the diaphragm were measured in four groups of inbred adult hamsters (greater than 40wk), randomly divided into sedentary control (SC), exercise control (EC), sedentary emphysematous (SE), and exercise emphysematous (EE) groups. Emphysema was induced by a single endotracheal instillation of elastase. Exercise consisted of running 1 h/day, 7 days/wk for 20 wk. Functional residual capacity (FRC), measured by means of a pressure box, was approximately 2.5 times greater in both emphysematous groups compared with control groups. Small diaphragmatic bundles were then isolated and subjected to in vitro analysis of isometric contractile properties. No differences were observed among the four groups in time to peak tension, half-relaxation time, and shape of the force-frequency curve. The diaphragmatic length-tension curve of emphysematous animals was displaced toward the left; maximal tetanic tension was similar in all groups, while optimal length (Lo), defined as the length at which maximal twitch tension occurred, was significantly shorter in both emphysematous groups. The Lo was negatively correlated with the FRC. Exercise tended to increase the in vitro endurance of the diaphragm bundles in control animals only. Diaphragms from both emphysematous groups, however, did show the greatest resistance to fatigue. It is concluded that 1) daily running for 1 h does not influence the diaphragmatic contractile properties in the hamster, but fatigue was reduced; 2) the load of chronic emphysema decreased the hamster's diaphragm fatiguability; and 3) the diaphragms of emphysematous hamsters chronically adapt by decreasing diaphragmatic length in proportion to the degree of hyperinflation and thus probably continue to operate at an Lo.

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Characteristics and functional significance of canine abdominal muscles

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.6.2427 ◽

1988 ◽

Vol 65 (6) ◽

pp. 2427-2433 ◽

Cited By ~ 20

Author(s):

G. A. Farkas ◽

D. F. Rochester

Keyword(s):

Abdominal Pressure ◽

Abdominal Muscles ◽

Active Length ◽

Residual Capacity ◽

Crural Diaphragm ◽

And Function ◽

Tension Curves ◽

Stimulation Of

To assess the characteristics and function of the muscles of the anterolateral abdominal wall, we have examined the isometric contractile properties of bundles of canine rectus abdominis (RA) and external oblique (EO) muscles. In addition, we have related the lengths of these muscles measured sonometrically in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We also investigated the action of the abdominal muscles on the displacement of costal and crural diaphragm. We found that 1) contraction time of RA was longer and that the RA developed greater force than the EO at submaximal stimulation frequencies; 2) maximal tetanic force and the active length-tension curves were similar in both abdominal muscles; 3) on passive stretch, the compliance of the RA was one-third that of the EO; 4) at supine FRC, the EO is operating at 83% of Lo, whereas the RA is operating at 105% of Lo; 5) stimulation of either RA or EO (abdominal pressure of 15 cmH2O) lengthened the costal and crural diaphragm toward their Lo values, with greater crural excursion occurring than costal. We conclude that the RA is well suited for restraining the abdominal viscera in prone quadrupeds, whereas the EO is better designed to assist expiration. Stimulation of both muscles improves in situ diaphragmatic operating length.

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Effects of salbutamol on rat diaphragm contractility

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.3.1103 ◽

1996 ◽

Vol 81 (3) ◽

pp. 1103-1110 ◽

Cited By ~ 12

Author(s):

H. F. Van der Heijden ◽

R. H. Van Balkom ◽

H. T. Folgering ◽

C. L. Van Herwaarden ◽

P. N. Dekhuijzen

Keyword(s):

Time Course ◽

Subcutaneous Administration ◽

Contractile Properties ◽

Force Generation ◽

Force Frequency ◽

Rat Diaphragm ◽

Tetanic Force ◽

Low Concentrations

The aim of this study was to investigate 1) the effects and time course of single doses of salbutamol on isometric contractile properties of isolated rat diaphragm strips and 2) whether these effects were caused by a direct effect on the muscle. Two experiments were performed. In one, salbutamol was administered subcutaneously in doses of 12.5, 25, 50, or 100 micrograms/kg (25 and 50 micrograms/kg sc resulted in serum concentrations of approximately 9 and approximately 15 micrograms/l, respectively, 0.5 h after injection) and in vitro contractile properties were determined 0.5, 1, 2, or 4 h after administration; in the other, salbutamol was added to the tissue bath in a concentration of < or = 2, approximately 10, approximately 20, and approximately 80 micrograms/l. Twice force, maximal tetanic force, and twitch force-to-tetanic force ratio all increased in a dose-dependent way in both experiments. The increases in force generation were slightly higher after subcutaneous administration. Force-frequency curves were shifted upward in both experiments. No significant effects of time of salbutamol administration were found, but the increase in force generation was most pronounced within 2 h after subcutaneous administration. In conclusion, in vitro force generation can be improved by low concentrations of salbutamol. The slightly higher increases in force generation after subcutaneous administration suggest that in vivo salbutamol may have additional positive inotropic actions on diaphragm contractility besides a direct beta 2-adrenergic effect on the muscle itself.

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Functional characteristics of canine costal and crural diaphragm

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.5.2253 ◽

1988 ◽

Vol 65 (5) ◽

pp. 2253-2260 ◽

Cited By ~ 33

Author(s):

G. A. Farkas ◽

D. F. Rochester

Keyword(s):

Contractile Properties ◽

Force Frequency ◽

Cross Sectional ◽

Volume Functional ◽

Generating Capacity ◽

Residual Capacity ◽

Crural Diaphragm ◽

Muscle Cross Sectional Area

We estimated the in situ force-generating capacity of the costal and crural portions of the canine diaphragm by relating in vitro contractile properties and diaphragmatic dimensions to in situ lengths. Piezoelectric crystals were implanted on right costal and left crural diaphragms of anesthetized dogs, via midline laparatomy. With the abdomen reclosed, diaphragm lengths were recorded at five lung volumes. Contractile properties of excised muscle bundles were then measured. In vitro force-frequency and length-tension characteristics of the costal and crural diaphragms were virtually identical; their optimal force values were 2.15 and 2.22 kg/cm2, respectively. In situ, at residual volume, functional residual capacity (FRC), and total lung capacity the costal diaphragm lay at 102, 95, and 60% of optimal length (Lo), whereas the crural diaphragm lay at 88, 84, and 66% of Lo. Muscle cross-sectional area was 40% greater in costal than in crural diaphragms. Considering in situ lengths, cross-sectional areas, and in vitro length-tension characteristics at FRC, the costal diaphragm could exert 60% more force than the crural diaphragm.

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Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

Nuklearmedizin ◽

10.1055/s-0038-1629552 ◽

1991 ◽

Vol 30 (01) ◽

pp. 35-39 ◽

Cited By ~ 1

Author(s):

H. S. Durak ◽

M. Kitapgi ◽

B. E. Caner ◽

R. Senekowitsch ◽

M. T. Ercan

Keyword(s):

Soft Tissue ◽

Room Temperature ◽

Normal Subjects ◽

Left Testis ◽

Wide Range ◽

Activity Ratios ◽

The Right ◽

Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

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Enhanced Increases in Cytosolic Ca2+ in ADP-Stimulated Platelets from Patients with Delta-Storage Pool Deficiency – A Possible Indicator of Interactions between Granule-Bound ADP and the Membrane ADP Receptor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655971 ◽

1997 ◽

Vol 77 (02) ◽

pp. 376-382 ◽

Cited By ~ 15

Author(s):

Bruce Lages ◽

Harvey J Weiss

Keyword(s):

Platelet Rich Plasma ◽

Limited Range ◽

Dense Granule ◽

Receptor Desensitization ◽

Fura 2 ◽

Storage Pool ◽

Low Levels ◽

The Right

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.

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Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens

Microorganisms ◽

10.3390/microorganisms9051107 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1107

Author(s):

Wonho Choi ◽

Yoshihiro Yamaguchi ◽

Ji-Young Park ◽

Sang-Hyun Park ◽

Hyeok-Won Lee ◽

...

Keyword(s):

Agrobacterium Tumefaciens ◽

Physiological Function ◽

Functional Characterization ◽

Site Directed Mutagenesis ◽

In Vitro Assays ◽

Cell Growth Inhibition ◽

The Right

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

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THEMIS Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis

Infection and Immunity ◽

10.1128/iai.02586-14 ◽

2014 ◽

Vol 83 (2) ◽

pp. 759-768 ◽

Cited By ~ 9

Author(s):

Sabrina Torre ◽

Sebastien P. Faucher ◽

Nassima Fodil ◽

Silayuv E. Bongfen ◽

Joanne Berghout ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Cerebral Malaria ◽

Functional Coupling ◽

Experimental Cerebral Malaria ◽

Content Type ◽

Proinflammatory Responses ◽

Inflammatory Bowel ◽

Blood Brain Barrier Integrity

We identify anN-ethyl-N-nitrosourea (ENU)-induced I23N mutation in the THEMIS protein that causes protection against experimental cerebral malaria (ECM) caused by infection withPlasmodium bergheiANKA.ThemisI23Nhomozygous mice show reduced CD4+and CD8+T lymphocyte numbers. ECM resistance inP. bergheiANKA-infectedThemisI23Nmice is associated with decreased cerebral cellular infiltration, retention of blood-brain barrier integrity, and reduced proinflammatory cytokine production. THEMISI23Nprotein expression is absent from mutant mice, concurrent with the decreased THEMISI23Nstability observedin vitro. Biochemical studiesin vitroand functional complementationin vivoinThemisI23N/+:Lck−/+doubly heterozygous mice demonstrate that functional coupling of THEMIS to LCK tyrosine kinase is required for ECM pathogenesis. Damping of proinflammatory responses inThemisI23Nmice causes susceptibility to pulmonary tuberculosis. Thus, THEMIS is required for the development and ultimately the function of proinflammatory T cells.ThemisI23Nmice can be used to study the newly discovered association ofTHEMIS(6p22.33) with inflammatory bowel disease and multiple sclerosis.

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Pharmacologically mechanistic basis for the traditional uses of Rumex acetosa in gut motility disorders and emesis

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i3.23406 ◽

2015 ◽

Vol 10 (3) ◽

pp. 548 ◽

Cited By ~ 3

Author(s):

Musaddique Hussain ◽

Shahid Masood Raza ◽

Khalid Hussain Janbaz

Keyword(s):

Rumex Acetosa ◽

Response Curves ◽

Motility Disorders ◽

Traditional Uses ◽

Antiemetic Activity ◽

Rabbit Jejunum ◽

Mechanistic Basis ◽

The Right

In vitro and in vivo studies were undertaken to evaluate the pharmacologically mechanistic background to validate the traditional uses of Rumex acetosa in the treatment of emesis and gastrointestinal motility disorders such as constipation and diarrhea. In rabbit jejunum preparation, methanolic extract of R. acetosa (0.01-1.0 mg/mL) caused a transient spasmogenic effect, followed by the spasmolytic effect (3-10 mg/mL). In presence of atropine, spasmogenic effect was blocked while spasmolytic effect was emerged, suggesting that spasmogenic effect was mediated through activation of muscarinic receptors. Extract inhibited the K+ (80 mM)-induced contraction, suggesting Ca2+-cha-nnel blockade, which was further confirmed when pretreatment of tissue with extract shifted the Ca2+ concentration-response curves to the right, similarly as verapamil. R. acetosa also exhibited the significant antiemetic activity (p<0.05) against different emetogenic stimuli, when compared with chlorpromazine. This study confirms the presence of gut modulator (spasmogenic and spasmolytic) and antiemetic activates, validating its traditional uses.

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