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Who continues using the diaphragm and who doesn't: implications for the acceptability of female-controlled HIV prevention methods.

OBJECTIVES: This study examines the acceptability of the diaphragm with the aim of facilitating the development of female-controlled human immunodeficiency virus (HIV) prevention methods. More specifically, we assess associations between being a current (vs. former) diaphragm user and characteristics that are hypothesized to influence the acceptability of contraceptive methods; and explore reasons for discontinuing use of the diaphragm among former diaphragm users. DESIGN: The study involved a cross-sectional telephone survey with women who were members of a nonprofit health maintenance organization and who were either a current (n = 215) or former (n = 172) diaphragm user. METHODS: Participants were interviewed about the importance of contraceptive attributes; perceptions for the diaphragm; diaphragm use self-efficacy; perceived risk of and motivation to avoid pregnancy, HIV, and other sexually transmitted infections; and demographic characteristics, sexual, and contraceptive behavior. RESULTS: The likelihood of being a current diaphragm user (vs. former) increased with age, greater confidence in being able to use the diaphragm, greater perceived risk of pregnancy and more positive perceptions of the diaphragm. Women who valued attributes of hormonal contraceptives were less likely to be current users. Former diaphragm users reported that the following reasons were moderately to extremely important in their decision to stop using the diaphragm: difficulty inserting or removing the diaphragm (50.8%), dislike of leaving the diaphragm inside the vagina (46.8%), and wanting a more effective method for preventing pregnancy (44.2%). CONCLUSIONS: The findings suggest that specific characteristics of a product influence continued use and have implications for improving the acceptability of existing and new female-controlled HIV prevention methods.

Adult↗

Inotrophic effects of the K(+) channel blocker TEA on dystrophic (mdx and dy/dy) mouse diaphragm.

K(+) channels regulate diaphragm resting membrane potential and action potential duration, and hence force. Certain blockers of these channels, e.g. tetraethylammonium (TEA), increase twitch force of normal diaphragm. To further address whether these agents may be useful in the treatment of diaphragm weakness, studies examined the effects of TEA on force of overtly diseased muscle. Diaphragm from two mouse models of muscular dystrophy (mdx and dy/dy) was studied in vitro. Diaphragm from both models was significantly weaker than diaphragm from control animals. TEA (10 mM) increased twitch force of both mdx diaphragm (P<0.005) and dy/dy diaphragm (P<0.0005), as well as force of diaphragm from non-diseased animals. The percent force increase of mdx diaphragm was at least as great as that of non-diseased muscle (15.3 vs 9.2%, P=0.14), and the percent force increase of dy/dy diaphragm was significantly greater than that of non-diseased muscle (22.7 vs 10.2%, P<0.02). Absolute force increases normalized for cross-sectional area were comparable for healthy and diseased diaphragm, however. These findings indicate that TEA increases force of both dystrophin-deficient and merosin-deficient dystrophic mouse diaphragm muscle.

Animals↗

Hypothesis that vagal reinervation of diaphragm could sensitise it to electrical stimulation.

The hypothesis proposed is that restoration of functional capacity of denervated diaphragm may be achieved by reinervating it with vagus nerve. Following trauma, carcinomatose infiltration, and/or large thoracic surgery and neck surgery, phrenic nerve is frequently injured. Reinervation even in the most favourable conditions would not follow and diaphragm would rest permanently denervated and paralysed. This results in unilateral or bilateral paralysis of diaphragm. In principle, intermittent electrical stimulation of the phrenic nerve or diaphragm could elicit regular diaphragm contractions and maintain satisfactory respiration. While this technique could be used in upper motor neurone injury, in lower motor neurone injury and denervated diaphragm, that imposes too high electrical resistance, direct diaphragm pacing is practically impossible. In these cases, long term artificial ventilation is often necessary. Nevertheless, those patients are at high risk to suffer from atelectasis and respiratory infections. We project a hypothesis that reinervation of denervated diaphragm by vagus nerve could re-establishes its sensitivity to intramuscular electrical stimulation and may allow stimulation of the diaphragm by implanted pace-maker electrodes. An appropriate electrical stimulation might then be possible and diaphragm pacing could replace prolonged artificial ventilation in those patients. Restoration of functional capacity of denervated diaphragm could open a perspective for long term diaphragm pacing in patients with irreversible phrenic nerve injury and diaphragm paralysis.

Diaphragm↗

Diaphragm structure and function in health and disease.

The diaphragm is the primary muscle of inspiration, and as such uncompromised function is essential to support the ventilatory and gas exchange demands associated with physical activity. The normal healthy diaphragm may fatigue during intense exercise, and diaphragm function is compromised with aging and obesity. However, more insidiously, respiratory diseases such as emphysema mechanically disadvantage the diaphragm, sometimes leading to muscle failure and death. Based on metabolic considerations, recent evidence suggests that specific regions of the diaphragm may be or may become more susceptible to failure than others. This paper reviews the regional differences in mechanical and metabolic activity within the diaphragm and how such heterogeneities might influence diaphragm function in health and disease. Our objective is to address five principal areas: 1) Regional diaphragm structure and mechanics (GAF). 2) Regional differences in blood flow within the diaphragm (WLS). 3) Structural and functional interrelationships within the diaphragm microcirculation (DCP). 4) Nitric oxide and its vasoactive and contractile influences within the diaphragm (MBR). 5) Metabolic and contractile protein plasticity in the diaphragm (SKP). These topics have been incorporated into three discrete sections: Functional Anatomy and Morphology, Physiology, and Plasticity in Health and Disease. Where pertinent, limitations in our understanding of diaphragm function are addressed along with potential avenues for future research.

Aging↗

Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm.

We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1; P < 0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms (P < 0.01), and a 19% increase (P < 0.05) in fibers expressing only the slow SERCA isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on diaphragm homogenates indicated that COPD diaphragms expressed only one-third the SERCA1 content noted in control diaphragms; in contrast, COPD and control diaphragms did not differ with respect to SERCA2 content. The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data (Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB. Am J Respir Crit Care Med 168: 706-713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm.

Calcium-Transporting ATPases↗

Ultrasound evaluation of the paralyzed diaphragm.

Ultrasound has been used to evaluate diaphragm thickness in the zone of apposition of the diaphragm to the rib cage. The purpose of this study was to determine if ultrasonography could distinguish between a paralyzed and normally functioning diaphragm. We predicted that a paralyzed diaphragm would be atrophic and not shorten, therefore it would be thin and not thicken during inspiration. Thirty subjects (five with bilateral diaphragm paralysis, seven with unilateral diaphragm paralysis, three with inspiratory weakness but normally functioning diaphragms, and 15 healthy control subjects) had diaphragm ultrasound performed with a 7.5 to 10.0 MHz transducer placed over the lower rib cage in the mid-axillary line. The thickness of the diaphragm (tdi) was measured to the nearest 0.1 mm at FRC (t(di)FRC) and TLC (t(di)TLC). Diaphragm thickening during inspiration (delta t(di)) was calculated as (t(di)TLC - t(di)FRC)/t(di)FRC. In patients with unilateral paralysis, t(di) and delta t(di) for the paralyzed hemidiaphragm were significantly less than those values for the normally functioning hemidiaphragm (1.7 +/- 0.2 mm versus 2.7 +/- 0.5 mm [mean + SD] p < 0.01 for t(di), and -8.5 +/- 13% versus 65 +/- 26% [p < 0.001] for delta t(di)). The t(di) and delta t(di) for patients with bilateral diaphragm paralysis were significantly less than those values for the healthy volunteers (1.8 +/- 0.2 versus 2.8 +/- 0.4 and -1 +/- 15% versus 37 +/- 9% for t(di) and delta t(di), respectively) (p < 0.001). We conclude that ultrasound measurements of t(di) and delta t(di) can be used to determine if a diaphragm is paralyzed and confirm our predictions that a chronically paralyzed diaphragm is atrophic and does not thicken during inspiration.

Adult↗

Effect of lung volume reduction surgery on diaphragm length in severe chronic obstructive pulmonary disease.

Lung volume reduction surgery (LVRS) has been suggested as improving respiratory mechanics in patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that LVRS might lengthen the diaphragm, increase its area of apposition with the chest wall, and thereby improve its mechanical function. To determine the effect of bilateral LVRS on diaphragm length, we measured diaphragm length at TLC, using plain chest roentgenograms (CXRs), in 25 patients (11 males and 14 females) before LVRS and 3 to 6 mo after LVRS. A subgroup of seven patients (reference data) also had diaphragm length measurements made with CXRs, using films made within a year before their presurgical evaluation. Right hemidiaphragm silhouette length (PADL) and the length of the most vertically oriented portion of the right hemidiaphragm muscle (VDML) were measured. Diaphragm dome height was determined from the: (1) distance between the dome and transverse diameter at the manubrium; and (2) highest point of the dome referenced horizontally to the vertebral column. Patients also underwent spirometry, measurements of lung volumes and diffusion capacity, an incremental symptom-limited maximum exercise test, and measurements of 6 min walk distance (6MWD) and transdiaphragmatic pressures during maximum static inspiratory efforts (Pdimax sniff) and bilateral supramaximal electrophrenic twitch stimulation (Pditwitch) both before and 3 mo after LVRS. Patients were 58 +/- 8 yr of age, with severe COPD and hyperinflation (FEV1 = 0.68 +/- 0.23 L, FVC = 2.56 +/- 7.3 L, and TLC = 143 +/- 22% predicted). Following LVRS, PADL increased by 4% (from 13.9 +/- 1.9 cm to 14.5 +/- 1.7 cm; p = 0.02), VDML increased by 44% (from 2.08 +/- 1.5 cm to 3.00 +/- 1.6 cm, p = 0.01), and diaphragm dome height increased by more than 10%. In contrast, diaphragm lengths were similar in subjects with CXRs made before LVRS and within 1 yr before evaluation. The increase in diaphragm length correlated directly with postoperative reductions in TLC and RV, and also with increases in transdiaphragmatic pressure with maximal sniff (Pdimax sniff), maximal oxygen consumption (V O2max), maximal minute ventilation (V Emax), and maximum voluntary ventilation following LVRS. We conclude that LVRS leads to a significant increase in diaphragm length, especially in the area of apposition of the diaphragm with the rib cage. Diaphragm lengthening after LVRS is most likely the result of a reduction in lung volume. Increases in diaphragm length after LVRS correlate with postoperative improvements in diaphragm strength, exercise capacity, and maximum voluntary ventilation.

Diaphragm↗

Effect of hypoxia on diaphragm blood flow, oxygen uptake, and contractility.

Recent studies examining the effects of hypoxia on diaphragm function have reached conflicting conclusions, with some reports suggesting an adverse effect of even mild hypoxemia while others indicate that the diaphragm may be extremely resistant to hypoxic stress. Diaphragm tension was not, however, directly measured nor was diaphragm length controlled in these previous reports, and it seems possible that methodologic limitations may have been responsible for these discrepant results. The purpose of the present study was to examine the effects of graded, steady-state hypoxia on diaphragm blood flow, oxygen extraction, oxygen consumption, and contractility using an in situ canine diaphragm strip preparation that permitted direct and continuous measurement of diaphragm length, tension, and blood flow. Measurements were made with the diaphragm at rest, during normoxia (PaO2, 90 to 160 mm Hg), mild hypoxia (PaO2, 45 to 60 mm Hg), and severe hypoxia (PaO2, 25 to 35 mm Hg); measurements were made with the diaphragm at rest, during rhythmic contractions at a tension time index (TTI) of 0.05, and with contractions at a TTI of 0.15. Decreases in arterial oxygenation resulted in progressive increases in blood flow and in the fractional extraction of oxygen in both resting and contracting diaphragm strips. At all levels of activity tested, blood flow and fractional extraction increased sufficiently to keep diaphragm oxygen consumption constant despite reductions in arterial oxygen content. Diaphragm contractility, as assessed from the tension generated in response to a range of electrical stimuli (1 to 80 Hz), was unaffected by hypoxia for trials performed with the diaphragm at rest and contracting at a TTI of 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of hypoxia on diaphragm activity in anesthetized rats.

Hypoxia is one of the most common conditions observed by PACU nurses after surgery. It may be caused by a reduced functional residual capacity, hypoventilation, and/or ventilation-perfusion mismatch. Hypoxia can also affect diaphragm contractility, making it difficult to wean postoperative patients from mechanical ventilation. Clinically, however, there is no method to directly measure diaphragm contractility; therefore, indicators of intrathoracic pressure such as tidal volume are used. The purpose of this study was to directly measure the effects of diaphragm shortening in 12 anesthetized Sprague-Dawley rats before, during, and after induced hypoxia. A miniaturized ultrasonic sensor was used to measure changes in diaphragm thickness as an index of diaphragm shortening. A stainless steel electrode was attached adjacent to the ultrasonic sensor and used to measure the electromyogram (EMG) of the diaphragm. After normoxic measurements were recorded, hypoxia was initiated by connecting the tracheal cannula to a latex balloon containing 7.4% oxygen in nitrogen. During the first 5 minutes of hypoxia, diaphragm shortening, EMG, and intrathoracic pressure increased. Over the next 30 to 100 minutes, EMG and intrathoracic pressure remained elevated, whereas diaphragm shortening decreased to 50% of control, which was defined as diaphragm fatigue. The mean time for hypoxia-induced diaphragm fatigue to occur was 63 minutes. These results indicate that hypoxia-induced decline in diaphragm shortening was not caused by a decrease in muscle excitation as measured by EMG. These data suggest that impairment in mechanical-chemical coupling (diaphragm shortening) could be a result of decreased oxygen availability associated with the lower arterial blood oxygen content. Thus, the increase in intrathoracic pressure throughout hypoxia suggests that intrathoracic pressure is not always a consistent index of the contractile state of the diaphragm.

Analysis of Variance↗

Properties of calcium currents and contraction in cultured rat diaphragm muscle.

The characterization of calcium currents and contraction simultaneously measured in cultured rat diaphragm muscle cells was carried out in the present study. Whole-cell patch-clamp experiments were designed to further elucidate the mechanism of excitation-contraction (E-C) coupling in diaphragm which, though generally considered a skeletal-type muscle, has been reported to exhibit properties indicative of a cardiac-like E-C coupling mechanism. Normalized current/voltage (I/V) curves for two concentrations of external calcium (2.5 and 5 mM) were obtained from diaphragm myoballs. Both curves showed peaks corresponding to the activation of a T-type calcium current and a dihydropyridine-sensitive L-type calcium current. The normalized curve for the voltage dependence of the activation of contraction in diaphragm myoballs followed a typical Boltzmann-type relationship to the peak of contraction. Thereafter, the curve declined in a manner that was more pronounced in diaphragm compared to that measured in additional experiments using cultured rat limb muscle myoballs. This effect could be interpreted in terms of a more pronounced participation of the L-type current in E-C coupling in cultured diaphragm muscle. An increased likelihood of cultured diaphragm muscle to undergo depletion of sarcoplasmic reticular calcium stores during repetitive stimulation, or a heightened propensity for the voltage sensor for E-C coupling in diaphragm to enter the inactive state could also explain this effect. Maximal contractile activity was only slightly affected when the L-type current was blocked by externally applied cadmium (2 mM) or cobalt (3 mM), suggesting that a pronounced calcium-current-dependent component of contraction is unlikely in cultured diaphragm muscle. These results show that T- and L-type calcium channels are expressed in cultured rat diaphragm muscle cells and that, in contrast to cardiac muscle, the entry of calcium ions via L-type voltage-dependent calcium channels is not a prerequisite for contraction. Differences in the voltage sensitivity of contraction, observed at depolarized membrane potentials in cultured rat diaphragm and limb muscle cells, suggest that the voltage sensor for E-C coupling in diaphragm might more readily enter an inactivated configuration - possibly by a mechanism which is dependent on the concentration of external calcium.

Animals↗

Costal diaphragm blood flow heterogeneity at rest and during exercise.

To gain insight into diaphragm functional heterogeneity, blood flow (expressed as ml.min-1 x 100 g-1) was measured using radiolabeled microspheres in the ventral, medial, and dorsal regions of the costal diaphragm and in the crural diaphragm of sedentary control (S) and exercise trained (ET) female Wistar-Kyoto rats at rest and during treadmill exercise. ET animals had performed moderate intensity exercise training on a motorized treadmill (22 m/min, 10% grade, 60 min/d) for 12 months, while S were cage-confined. The efficacy of exercise training was demonstrated by a 12% increase (P < 0.05) in ventricular weight-to-body weight ratio and increases (P < 0.05) in citrate synthase activity in hindlimb skeletal muscles of ET. At rest, blood flow in the ventral costal diaphragm (16 +/- 1) averaged approximately 61% of that in the medial (26 +/- 3) and dorsal (25 +/- 2) costal regions (P = 0.035), and crural diaphragm flow was 23 +/- 3. During treadmill exercise (5 min at 22 m/min, 10% incline), blood flow increased an average of 5-fold (P < 0.001) throughout the diaphragm, but the heterogeneous flow pattern persisted; i.e., blood flow remained lower (P = 0.003) in the ventral region (77 +/- 7) than either the medial (135 +/- 15) or dorsal (127 +/- 11) costal regions. Flow in the crural diaphragm during exercise was intermediate (105 +/- 9). Exercise training did not alter either the magnitude of blood flows or the flow distribution pattern within the diaphragm. Citrate synthase activity was two-fold that of the plantaris muscle and was uniform across the ventral, medial, and dorsal costal and the crural diaphragm of a second group of age-matched rats (P = 0.57). These data demonstrate that, although oxidative capacity is uniform throughout the diaphragm, there is a significant regional heterogeneity of blood flow within the rat diaphragm both at rest and during locomotory exercise. The greater flow in the medial and dorsal regions of the costal diaphragm suggests that these regions sustain a greater portion of the inspiratory work load at rest and during exercise compared to the ventral region.

Animals↗

Comparative analysis of the effectiveness of the diaphragm and birth control pill during the first year of use among suburban adolescents.

Little attention has been paid to the diaphragm as a contraceptive option for adolescents. To compare diaphragm and birth control pill use by adolescents, 124 females (aged 13-20 years) in a suburban-based adolescent health service were interviewed at least one year after receiving a contraceptive prescription. The 73 diaphragm choosers did not differ from the 51 pill choosers in age, race, or reason for their original visit to the health service. Diaphragm choosers, however, were better students, of higher socioeconomic status, and had had fewer prior pregnancies. In the year following prescription, continuous use for 12 months was reported by 43% of diaphragm choosers and 45% of pill choosers, with significantly more pill (26%) than diaphragm (8%) choosers reporting discontinued use for at least one month while remaining sexually active. Regular use (diaphragm every intercourse, missing less than or equal to 1 pill/month) was reported by 36% of diaphragm choosers compared to 88% of pill choosers; and at least one pregnancy during the year was reported by 15% of diaphragm choosers and 18% of pill choosers. At follow-up interviews, diaphragm subjects disliked the immediate annoyances of the diaphragm, and pill users expressed concern about the potential side effects of the pill. No single factor or set of factors correlated with continuous and regular use of either method. Because both methods present specific problems for certain patients, we suggest that in addition to the pill, the diaphragm should receive serious consideration as a contraceptive option for adolescents.

Adolescent↗

Effects of continuous positive airway pressure on diaphragm dimensions in preterm infants.

OBJECTIVE: The use of continuous positive airway pressure (CPAP) in the treatment of a variety of neonatal respiratory conditions is associated with improvement in arterial oxygen saturation, decreased long-term morbidity, and an overall improvement in infant survival. We reasoned that CPAP might change diaphragm length by increasing end-expiratory lung volume (EEV), but the extent to which this occurs has not been assessed. This study was designed to evaluate (1) the extent to which CPAP shortens the diaphragm and (2) the relationship of diaphragm thickness and excursion with arterial oxygen saturation in spontaneously breathing preterm infants. STUDY DESIGN: Ultrasonographically (7.5 MHz transducer), diaphragm thickness and diaphragm excursion were measured in 12 stable preterm infants [birth weight 1120+/-225 g (mean+/-SD); study weight 1187+/-400 g; gestational age 29+/-1 week; postnatal age 10+/-8 days, six males and six females] at three levels of CPAP [1-3, 4-6, and 7-9 cm H(2)O (low, medium, and high, respectively)]. Heart rate, respiratory rate, and arterial oxygen saturation were simultaneously recorded. RESULTS: We found that diaphragm thickness and arterial oxygen saturation increased, and diaphragm excursion decreased significantly at higher levels of CPAP (p<0.05). The shortening of the diaphragm at the high levels of CPAP, calculated from the increase in diaphragm thickness, was 36% at EEV and 31% at end-inspiratory volume. CONCLUSION: We conclude that the improvement in arterial oxygen saturation with CPAP occurred despite the presence of a shorter and a less mobile diaphragm, and that other physiological and mechanical alterations accompanying the application of CPAP offset its negative effects on diaphragm function. We speculate that with excessive CPAP, however, diaphragm dysfunction along with the previously described adverse hemodynamic effects may outweigh its benefits on oxygenation.

Diaphragm↗

Corticosteroids decrease mRNA levels of SERCA pumps, whereas they increase sarcolipin mRNA in the rat diaphragm.

1. In order to explore the potential role of the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA)-type pumps and of their modulators phospholamban (PLB) and sarcolipin (SLN) in the functional alterations of the diaphragm induced by corticosteroid treatment, expression of SERCA, PLB and SLN was assessed by RT-PCR in the diaphragm of rats treated daily for 5 days either with triamcinolone (80 mg kg-1, n = 8) or with saline (control; 0.6 ml, n = 8). 2. Triamcinolone treatment reduced the normalised overall amount of all SERCA mRNA in diaphragm by 70 % compared to controls (P < 0.05). This reduction was accounted for by a relatively larger decrease in the SERCA1 mRNA (-69 %, P < 0.05) whilst the decrease in SERCA2 mRNA (-49 %, P = 0.09) did not reach statistical significance. As a result the relative proportion of SERCA2 mRNA was increased from 43 +/- 7 % in control diaphragm to 52 +/- 4 % after triamcinolone treatment (P < 0.05). 3. Only the adult isoform of SERCA1 (i.e. SERCA1a) mRNA was found in the diaphragm of the 15-week-old control rats. Furthermore, triamcinolone treatment resulted in reduced levels of SERCA2a (-40 %, P < 0.05) and increased levels of SLN mRNA (+100 %, P < 0.05), while the decrease in PLB mRNA (-31 %, P = 0.277) did not reach statistical significance. SERCA1b, SERCA2b and SERCA3 mRNA levels fell below the detection limit in the diaphragm of both control and triamcinolone-treated rats. 4. Compared to control diaphragm, control rat heart showed a relatively high PLB/(SERCA1 + SERCA2) mRNA ratio of 7.88 while this ratio amounted only to 0.16 in control extensor digitorum longus (EDL) muscle. Remarkably, the SLN/(SERCA1 + SERCA2) mRNA ratio in normal cardiac muscle (0.96) was nearly the same as in diaphragm, but in EDL it amounted to only 0.05 that in diaphragm. This indicates the very low expression of SLN in rat EDL. 5. These data reveal that considerable alterations in SERCA mRNA levels accompany the functional changes seen in diaphragm after corticosteroid treatment. The relatively larger decrease in SERCA1 mRNA is in agreement with the selective type II fibre atrophy previously observed in the diaphragm of triamcinolone-treated rats, but the magnitude of SERCA alterations is more pronounced than expected on the basis of the structural changes in the diaphragm. The increase in SLN mRNA levels may represent a compensatory mechanism.

Adrenal Cortex Hormones↗

Shape and tension distribution of the active canine diaphragm.

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 approximately 6.5 cmH2O, and tensions were nonuniform in the diaphragm. Maximum principal stress sigma(1) of central tendon was found to be greater than sigma(1) of the costal region, and that was greater than sigma(1) 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 sigma(2) 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, sigma(1) was approximately 3-fold sigma(2), whereas in the central tendon, sigma(1) was only approximately 1.5-fold sigma(2.).

Animals↗

Regional variation in canine diaphragm thickness.

To quantify the relationship between both regional and overall diaphragm morphometry and body weight in the dog, diaphragm thickness was measured in five regions of the costal diaphragm and three regions of the crural diaphragm in 40 healthy dogs (8-40 kg). Surface area of the diaphragm, diaphragm weight, and body weight were also determined. Diaphragm surface area and weight varied linearly with body weight, but there was no significant correlation between overall diaphragm thickness and body weight. Diaphragm thickness varied significantly between regions, and three regions had systematic left-to-right differences as well. Because diaphragm geometry influences the diaphragm's function as a pressure generator, regional differences in thickness may alter the relationship between the force developed by the activation of a particular region of the diaphragm and its action on the respiratory system.

Animals↗

Effect of ischemia-reperfusion on diaphragm strength and fatigability.

Although episodes of prolonged limb skeletal muscle ischemia followed by periods of reperfusion and reoxygenation are known to elicit free radical-mediated injury, the susceptibility of the diaphragm to this form of injury is not known. The purpose of the present study was to determine the effects of a period of severe partial ischemia, followed by reperfusion, on diaphragm contractile function. We also examined the effect of administration of a free radical scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia-reperfusion. Experiments were performed on three groups of anesthetized dogs in which a vascularly isolated strip of diaphragm was dissected in situ: 1) a control group in which the diaphragm was perfused at the ambient systemic pressure, 2) a group in which the diaphragm was made ischemic for 3 h and reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and reperfusion. In all groups, we measured diaphragm strip strength and fatigability; we also assessed diaphragm blood flow at several levels of contractile activity. Periods of ischemia, followed by reperfusion, were found to produce a downward shift of the diaphragm force-frequency relationship and also to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at low levels of contractile activity was unaffected by ischemia-reperfusion, but the flow achieved during fatiguing contractions was appreciably lower than that in nonischemic control animals. DMSO administration protected the diaphragm from the effects of ischemia-reperfusion, preventing alterations in fatigability and strength. Diaphragm flow in DMSO-treated animals was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Finite-element analysis of stress in the canine diaphragm.

Stress in the diaphragm, transdiaphragmatic pressure, and diaphragm shape are interrelated by a balance of forces. Using precise in vivo measurements of diaphragm shape and transdiaphragmatic pressure distribution in combination with finite-element analysis (ANSYS), we determined the direction and magnitude of stress in the passive diaphragm at relaxation volume. Lead spheres sutured along muscle bundles identified muscle bundle location and orientation in vivo. The x, y, and z coordinates of the lead spheres and entire surface of the diaphragm, excluding the zone of apposition, were determined to within 1.4 mm. Thin shell elements were used to construct a finite-element model of the diaphragm with a 2.1- to 4.2-mm internodal spacing. The diaphragm was assumed to have a uniform thickness of 2.5 mm, and magnitude and direction of the principal stresses were computed. The results show that 1) diaphragm stress is nonuniform and anisotropic (i.e., varies both with location on diaphragm surface and direction examined), 2) largest stress (sigma 1) is aligned with muscle bundles and is two to four times larger than sigma 2 (perpendicular to sigma 1 in diaphragm plane), and 3) stress along the muscle bundles is larger in vivo under conditions of biaxial stress than at same length in vitro under uniaxial stress. Although diaphragm stress and tension have often been assumed to be uniform, our finding that stress is oriented primarily along the muscle fibers should be considered in future models of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗