Changes In Contractile Proteins Research Articles

The root of the matter: nitrate-rich beetroot juice reduces skeletal muscle O2 uptake during exercise.

The root of the matter: nitrate-rich beetroot juice reduces skeletal muscle O2 uptake during exercise.

A Multiple Step Active Stiffness Integration Scheme to Couple a Stochastic Cross-Bridge Model and Continuum Mechanics for Uses in Both Basic Research and Clinical Applications of Heart Simulation.

In a multiscale simulation of a beating heart, the very large difference in the time scales between rapid stochastic conformational changes of contractile proteins and deterministic macroscopic outcomes, such as the ventricular pressure and volume, have hampered the implementation of an efficient coupling algorithm for the two scales. Furthermore, the consideration of dynamic changes of muscle stiffness caused by the cross-bridge activity of motor proteins have not been well established in continuum mechanics. To overcome these issues, we propose a multiple time step scheme called the multiple step active stiffness integration scheme (MusAsi) for the coupling of Monte Carlo (MC) multiple steps and an implicit finite element (FE) time integration step. The method focuses on the active tension stiffness matrix, where the active tension derivatives concerning the current displacements in the FE model are correctly integrated into the total stiffness matrix to avoid instability. A sensitivity analysis of the number of samples used in the MC model and the combination of time step sizes confirmed the accuracy and robustness of MusAsi, and we concluded that the combination of a 1.25 ms FE time step and 0.005 ms MC multiple steps using a few hundred motor proteins in each finite element was appropriate in the tradeoff between accuracy and computational time. Furthermore, for a biventricular FE model consisting of 45,000 tetrahedral elements, one heartbeat could be computed within 1.5 h using 320 cores of a conventional parallel computer system. These results support the practicality of MusAsi for uses in both the basic research of the relationship between molecular mechanisms and cardiac outputs, and clinical applications of perioperative prediction.

Contractility and Myofibrillar Content in Skeletal Muscle are Decreased During Post-Sepsis Recovery, But Not During the Acute Phase of Sepsis.

Convalescence in humans after severe sepsis occurs over weeks to months and is associated with prolonged functional disabilities and impaired quality-adjusted survival. While much is known regarding the acute early phase of sepsis, there is a knowledge gap pertaining to restoration of muscle mass and function after elimination of the septic nidus. We used a sepsis-recovery model-where cecal-ligation-puncture (CLP) was performed in adult male mice followed 24 h later by removal of the cecum and antibiotic treatment-to assess changes in the abundance of muscle contractile proteins and function during the acute phase of sepsis (24 h post-CLP) and during the recovery phase (day 10 post-CLP). Although body weight and food consumption decreased acutely with sepsis, both had normalized by day 10; however, extensor digitorum longus mass remained decreased 10%. During acute sepsis, there were few contractile defects or significant changes in contractile proteins. In contrast, during sepsis recovery, specific maximum isometric twitch and specific maximum tetanic force were decreased ≈50%, compared with time-matched pair-fed controls, and defects were independent of the concomitant reduction in muscle mass. Force generation in sepsis-recovery mice was decreased 30% with increasing stimulus frequency. Contractile defects during sepsis-recovery were associated with 50% to 90% reductions in thin filament (troponin T, troponin I, tropomyosin, α-sarcomeric actin), thick filament (myosin heavy and myosin light chains), Z-disc (α-actinin 3), and M-band (myomesin-2) proteins, but no change in the intermediate filaments desmin and vimentin. During sepsis recovery, myofibrillar protein synthesis did not differ from control, but synthesis of sarcoplasmic proteins was increased 60%. These data suggest intrinsic defects in muscle contractile function exist during the recovery phase of sepsis and may negatively impact convalescence.

CHANGES OF MYOCARDIUM CONTRACTILITY ASSOCIATED WITH A SUBCHRONIC LEAD INTOXICATION IN RATS

Introduction. There is a high chance of a link between cardiovascular conditions and occupational or environmental exposure to lead. Taking into account the peculiarities of lead intoxication and the metal common occurrence it appeared to necessarily prove further experimental research of lead cardiotoxicity. Material and methods. After repeated intraperitoneal administration of sublethal doses of lead acetate to outbred male rats 3 times a week for 5 weeks, there was obtained the moderately pronounced subchronic lead intoxication manifested by some characteristic features. Cardiotoxic effects on myocardial contractility were studied by the analysis of the mechanical activity of isolated preparations of right ventricular trabeculae and papillary muscles contracting in isotonic and physiological modes of loading. Myocardial contractile function was also studied at the molecular level by measuring the sliding velocity of reconstructed thin filaments over myosin. Results. In papillary muscles lead intoxication led to a decrease in the maximal rate of isotonic shortening for all afterloads and a decrease in the thin filament sliding velocity in the in vitro motility assay. The same type of muscle from lead-exposed rats displayed marked changes in most of the main characteristics of afterload contraction-relaxation cycles, but in trabeculae, these changes were less pronounced. The reported changes were attenuated to some extent in rats similarly exposed to lead while being treated with a Ca-containing bio protector. The amount of work produced by both muscle preparations was unchanged under lead intoxication over the entire range of afterloads, which is an evidence of adaptation to the production of adequate mechanical work despite resulting contractility disturbances. Conclusions. 1. Subchronic lead intoxication was shown to cause contractile dysfunction of rat myocardium. In papillary muscles the alterations were observed more than in trabeculae. The changes in contractile proteins corresponded with those seen in myocardium structures. 2. The reported changes were attenuated to some extent in rats being treated with a Ca-containing bio protector.

Abstract 904: Disrupted Mechanobiology Links the Molecular and Cellular Phenotypes in Familial Dilated Cardiomyopathy

Familial dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death and a major indicator for heart transplant. The disease is frequently caused by mutations of sarcomeric proteins; however, one of the outstanding challenges in the field has been connecting mutation-induced changes in molecular function with the phenotype seen in cardiomyocytes. Many of the DCM mutation-induced changes in contractility at the molecular scale are subtle, begging the question of what other factors could link molecular-scale changes in contractile proteins with the cellular phenotype. We hypothesized that disease-causing mutations of sarcomeric proteins would likely affect not only contraction, but also how cardiomyocytes sense and respond to changes in their mechanical environment associated with aging and disease. To test this hypothesis, we studied the molecular and cellular consequences of a DCM mutation in troponin-T, deltaK210. We determined the molecular mechanism of deltaK210 using biochemical and biophysical tools, and then we used computational modeling to predict that the mutation should reduce the force per sarcomere in cells. In mutant human stem cell derived cardiomyocytes, we found that deltaK210 not only reduces contractility, but also causes cellular hypertrophy and impairs cardiomyocytes’ ability to adapt to changes in substrate stiffness (e.g., heart tissue fibrosis that occurs with aging and disease). These results link the molecular and cellular phenotypes and implicate impaired mechanosensing as an under-appreciated mechanism in the pathogenesis and progression of dilated cardiomyopathies. These results also have important implications for our understanding of multiple heart diseases and the design of precision therapeutics.

The Myometrium: From Excitation to Contractions and Labour.

We start by describing the functions of the uterus, its structure, both gross and fine, innervation and blood supply. It is interesting to note the diversity of the female's reproductive tract between species and to remember it when working with different animal models. Myocytes are the overwhelming cell type of the uterus (>95%) and our focus. Their function is to contract, and they have an intrinsic pacemaker and rhythmicity, which is modified by hormones, stretch, paracrine factors and the extracellular environment. We discuss evidence or not for pacemaker cells in the uterus. We also describe the sarcoplasmic reticulum (SR) in some detail, as it is relevant to calcium signalling and excitability. Ion channels, including store-operated ones, their contributions to excitability and action potentials, are covered. The main pathway to excitation is from depolarisation opening voltage-gated Ca2+ channels. Much of what happens downstream of excitability is common to other smooth muscles, with force depending upon the balance of myosin light kinase and phosphatase. Mechanisms of maintaining Ca2+ balance within the myocytes are discussed. Metabolism, and how it is intertwined with activity, blood flow and pH, is covered. Growth of the myometrium and changes in contractile proteins with pregnancy and parturition are also detailed. We finish with a description of uterine activity and why it is important, covering progression to labour as well as preterm and dysfunctional labours. We conclude by highlighting progress made and where further efforts are required.

Dissecting the Molecular Mechanism for Familial Cardiomyopathies

The heart needs to generate sufficient force and power to pump blood to the body and to adjust its power output in response to stresses. Mutations of contractile proteins, such as cardiac troponin T, can lead to familial cardiomyopathies, the leading cause of sudden cardiac death in people under the age of 30. Two common forms of cardiomyopathy, hypertrophic (HCM) and dilated (DCM) are characterized by thickening or thinning of the ventricular wall, respectively. However, how changes in contractile proteins at the molecular level lead to the disease phenotype is not well understood. To address this problem, we examined two point mutations in human cardiac troponin T (TnT), R92Q and ΔK210, which cause hypertrophic and dilated cardiomyopathy, respectively, in human patients. We have reconstituted the calcium-based regulation of actomyosin in vitro using tissue purified and recombinant cardiac proteins. Similar to previous studies, in vitro motility assays which reconstitute the calcium-dependent interactions between myosin and regulated thin filaments revealed that R92Q is shifted towards submaximal calcium activation while ΔK210 is shifted towards supermaximal calcium activation. We dissected the molecular mechanism of these differential changes using a combination of fluorescence equilibrium titrations and stopped-flow experiments, and show that these effects are due to alterations in the free energies of the biochemical transitions that regulate muscle activation. In particular, we see that these mutations differentially affect calcium-dependent positioning of tropomyosin along the thin filament. We propose that these changes affect the regulation of force production by the molecular motor myosin, leading to alterations in mechanosensing by heart tissue.

Remodeling of the rat distal colon in diabetes: function and ultrastructure.

This study seeks to define and explain remodeling of the distal colon in the streptozotocin (STZ)-treated rat model of diabetes through analysis of resting and active length dependence of force production, chemical composition, and ultrastructure. Compared with untreated controls, the passive stiffness on extension of the diabetic muscle is high, and active force produced at short muscle lengths is amplified but is limited by an internal resistance to shortening. The latter are accounted for by a significant increase in collagen type 1, with no changes in types 3 and 4. In the diabetic colon, ultrastructural studies show unique, conspicuous pockets of collagen among muscle cells, in addition to a thickened basement membrane and an extracellular space filled with collagen fibers and various fibrils. Measurements of DNA and total protein content revealed that the diabetic colon underwent hypertrophy, along with a proportional increase in actin and myosin contents, with no change in the actin-to-myosin ratio. Active force production per cross-sectional area was not different in the diabetic and normal muscles, consistent with the proportionality of changes in contractile proteins. The stiffness and the limit to shortening of the diabetic colon were significantly reduced by treatment with the glycation breaker alagebrium chloride (ALT-711), with no change in collagen contents. Functionally, this study shows that, in diabetes, the production of collagen type 1 and glycation increase stiffness, which limits distensibility on filling and limits shortening and expulsion of contents, both of which can be alleviated by treatment with ALT-711.

Time course analysis of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat.

Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time-resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long-term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9-14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X-ray diffraction analyses demonstrate that myosin can bind to actin in an ATP-dependent manner even after 9-14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post-translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long-term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm structure/function and underlying mechanisms at the gene, protein and cellular levels in response to CMV at a high temporal resolution ranging from 6 h to 14 days.

Abstract 18753: Mechanisms of Left Ventricular Reverse Remodeling: Insights From a Novel Murine Model of Hypertensive Ischemic Cardiomyopathy

Background: All approved therapies for heart failure (HF) lead to reverse LV remodeling (LVRR). The lack of genetically tractable animal models of LVRR has prevented further understanding of the biology of LVRR. Here we present a murine model of HF that mimics hypertensive ischemic cardiomyopathy, which undergoes LVRR with hemodynamic unloading. Methods: Wild type mice were subjected to Sham (n=6), or transverse aortic constriction (TAC) with LAD ligation (MI), leading to progressive LV remodeling (n=12). Hemodynamic unloading was accomplished by debanding (DB) the aorta 2 wks post MI/TAC (n=6), whereas the band remained intact in the HF group (n=6). Both DB and HF groups were followed for 4 more weeks. 2D echo speckle tracking was performed at 1 & 14 days post-MI/TAC, and at 4 wks post-DB. Hearts were analyzed by LV morphometry, histology and transcriptional profiling. Results: 2-D echo at 1 and 14 days post-MI/TAC showed progressive LV dilatation (1d=34ul, 14d=62ul; p<0.01). LVRR occurred 4 wks post-DB, with near normalization of LV volumes (p=NS vs sham). In contrast, LV volumes increased ~ 3-fold (p<0.01 vs sham) in the HF group. LV ejection fraction (LVEF) continued to decrease over 4 weeks in HF hearts (36% vs 31%, p<0.05), whereas LVEF increased in post-DB hearts (33% vs 42%, p<0.01). LV weights were significantly (p < 0.05) smaller in the DB group (85±13g) compared to the HF group (133±16g) at 4 weeks. Myocyte size decreased significantly (p<0.05) in DB hearts (409±41μ 2 ) compared to HF hearts (446±41μ 2 ), whereas interstitial fibrosis was not different (p > 0.05). Transcriptional profiling showed that, relative to HF hearts, LVRR in post DB hearts was accompanied by significant (p < 0.05) decreases in extracellular matrix gene expression, and significant increases in α-myosin heavy chain, calcium channels and adenylate cyclase gene expression. Conclusion: We developed a genetically tractable mouse model of hypertensive ischemic cardiomyopathy that undergoes LVRR following unloading. LVRR is accompanied by favorable changes in LV structure and function, myocyte size, as well as changes in contractile protein and calcium handling genes. Genetic manipulation of this model will permit a clearer understanding of the molecular mechanisms responsible for LVRR.

Contribution of increased VEGF receptors to hypoxic changes in fetal ovine carotid artery contractile proteins

Recent studies suggest that vascular endothelial growth factor (VEGF) can modulate smooth muscle phenotype and, consequently, the composition and function of arteries upstream from the microcirculation, where angiogenesis occurs. Given that hypoxia potently induces VEGF, the present study explores the hypothesis that, in fetal arteries, VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins. Pregnant ewes were acclimatized at sea level or at altitude (3,820 m) for the final 110 days of gestation. Endothelium-denuded carotid arteries from full-term fetuses were used fresh or after 24 h of organ culture in a physiological concentration (3 ng/ml) of VEGF. After 110 days, hypoxia had no effect on VEGF abundance but markedly increased abundance of the Flk-1 (171%) and Flt-1 (786%) VEGF receptors. Hypoxia had no effect on smooth muscle α-actin (SMαA), decreased myosin light chain (MLC) kinase (MLCK), and increased 20-kDa regulatory MLC (MLC(20)) abundances. Hypoxia also increased MLCK-SMαA, MLC(20)-SMαA, and MLCK-MLC(20) colocalization. Compared with hypoxia, organ culture with VEGF produced the same pattern of changes in contractile protein abundance and colocalization. Effects of VEGF on colocalization were blocked by the VEGF receptor antagonists vatalanib (240 nM) and dasatinib (6.3 nM). Thus, through increases in VEGF receptor density, hypoxia can recruit VEGF to help mediate remodeling of fetal arteries upstream from the microcirculation. The results support the hypothesis that VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins.

Skeletal muscle tissue from the Goto-Kakizaki rat model of type-2 diabetes exhibits increased levels of the small heat shock protein Hsp27

In order to increase our understanding of diabetes-related muscle weakness, we carried out a mass spectrometry-based proteomic analysis of skeletal muscle preparations from the Goto-Kakizaki rat model of type-2 diabetes. Fluorescence difference in-gel electrophoresis was performed to determine potential differences in the global protein expression profile of muscle extracts. Besides changes in contractile proteins and metabolic enzymes, the abundance of the small stress proteins αB-crystallin and Hsp27 was significantly increased. The up-regulation of the low-molecular-mass heat shock protein Hsp27 was confirmed by an alternative fluorescent staining method of two-dimensional gels and immunoblotting. The observed protein alterations in the cellular stress response, distinct metabolic pathways, regulatory mechanisms and the contractile apparatus might be directly or indirectly associated with peripheral resistance to insulin signalling, making these newly identified muscle proteins potential biomarkers of type-2 diabetes. Increased levels of molecular chaperones suggest considerably enhanced cellular stress levels in diabetic muscle fibres.

Chronic intermittent hypoxia increases left ventricular contractility in C57BL/6J mice

Intermittent hypoxia (IH) commonly occurs in patients with obstructive sleep apnea and can cause a wide range of pathology, including reduced left ventricular (LV) ejection fraction in rats as determined by echocardiography, in rodent models. We utilized echocardiography and pressure-volume (PV) loop analyses to determine whether LV contractility was decreased in inbred C57BL/6J mice exposed to IH and whether blockade of beta-adrenergic receptors modified the response to hypoxia. Adult male 9- to 10-wk-old mice were exposed to 4 wk of IH (nadir inspired O(2) 5-6% at 60 cycles/h for 12 h during the light period) or intermittent air (IA) as control. A second group of animals were exposed to the same regimen of IH or IA, but in the presence of nonspecific beta-blockade with propranolol. Cardiac function was assessed by echocardiography and PV loop analyses, and mRNA and protein expression in ventricular homogenates was determined. Contrary to our expectations, we found with PV loop analyses that LV ejection fraction (63.4 +/- 3.5 vs. 50.5 +/- 2.6%, P = 0.015) and other measures of LV contractility were increased in IH-exposed animals compared with IA controls. There were no changes in contractile proteins, atrial natriuretic peptide levels, LV posterior wall thickness, or heart weight with IH exposure. However, cAMP levels were elevated after IH, and propranolol administration attenuated the increase in LV contractility induced by IH exposure. We conclude that, contrary to our hypothesis, 4 wk of IH exposure in C57BL/6J mice causes an increase in LV contractility that occurs independent of ventricular hypertrophy and is, in part, mediated by activation of cardiac beta-adrenergic pathways.

Age-related decline in actomyosin structure and function

This review focuses on the role of changes in the contractile proteins actin and myosin in age-related deterioration of skeletal muscle function. Functional and structural changes in contractile proteins have been determined indirectly from specific force and unloaded shortening velocity of permeabilized muscle fibers, and were detected directly from site-directed spectroscopy in muscle fibers and from biochemical analysis of purified actin and myosin. Contractile proteins from aged and young muscle differ in (a) myosin and actomyosin ATPase activities, (b) structural states of myosin in contracting muscle, (c) the state of oxidative modifications. The extent of age-related physiological and molecular changes is dependent on the studied animal, the animal’s age, and the type of muscle. Therefore, understanding the aging process requires systematic, multidisciplinary studies on physiological, biochemical, structural, and chemical changes in specific muscles.

Differential activation of stress‐responsive signalling proteins associated with altered loading in a rat skeletal muscle

Skeletal muscle undergoes a significant reduction in tension upon unloading. To explore intracellular signalling mechanisms underlying this phenomenon, we investigated twitch tension, the ratio of actin/myosin filaments, and activities of key signalling molecules in rat soleus muscle during a 3-week hindlimb suspension and 2-week reloading. Twitch tension and myofilament ratio (actin/myosin) gradually decreased during unloading but progressively recovered to initial levels during reloading. To study the involvement of stress-responsive signalling proteins during these changes, the activities of protein kinase C alpha (PKCalpha) and three mitogen-activated protein kinases (MAPKs)--c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38 MAPK--were examined using immunoblotting and immune complex kinase assays. PKCalpha phosphorylation correlated positively with the tension (Pearson's r = 0.97, P < 0.001) and the myofilament ratio (r = 0.83, P < 0.01) over the entire unloading and reloading period. Treatment of the soleus muscle with a PKC activator resulted in a similar paralleled increment in both PKCalpha phosphorylation and the alpha-sarcomeric actin expression. The three MAPKs differed in the pattern of activation in that JNK activity peaked only for the first hours of reloading, whereas ERK and p38 MAPK activities remained elevated during reloading. These results suggest that PKCalpha may play a pivotal role in converting loading stress to intracellular changes in contractile proteins that determine muscle tension. Differential activation of MAPKs may also help alleviate muscle damage, modulate energy transport and/or regulate the expression of contractile proteins upon altered loading.

Structural Transients of Contractile Proteins upon Sudden ATP Liberation in Skeletal Muscle Fibers

Structural changes of contractile proteins were examined by millisecond time-resolved two-dimensional x-ray diffraction recordings during relaxation of skinned skeletal muscle fibers from rigor after caged ATP photolysis. It is known that the initial dissociation of the rigor actomyosin complex is followed by a period of transient active contraction, which is markedly prolonged in the presence of ADP by a mechanism yet to be clarified. Both single-headed (overstretched muscle fibers with exogenous myosin subfragment-1) and two-headed (fibers with full filament overlap) preparations were used. Analyses of various actin-based layer line reflections from both specimens showed the following: 1), The dissociation of the rigor actomyosin complex was fast and only modestly decelerated by ADP and occurred in a single exponential manner without passing through any detectable transitory state. Its ADP sensitivity was greater in the two-headed preparation but fell short of explaining the large ADP effect on the transient active contraction. 2), The decay of the activated state of the thin filament followed the time course of tension more closely in an ADP-dependent manner. These results suggest that the interplay between the reattached active myosin heads and the thin filament is responsible for the prolonged active contraction in the presence of ADP.

Leukaemia inhibitory factor alters expression of genes involved in rat cardiomyocyte energy metabolism

Cardiac remodelling is associated with changes in contractile proteins and their performance, alterations in energy production and intracellular calcium homeostasis, as well as changes in extracellular matrix proteins. Some of these processes may be mediated through the gp130 receptor complex. Patients with heart failure have increased cardiac gene expression of leukaemia inhibitory factor (LIF), a cytokine that signals through the gp130 receptor. The aim of this study was to identify alterations in gene expression in LIF-stimulated neonatal cardiomyocytes. Cardiomyocytes were isolated from 1- to 3-day-old Wistar rats and stimulated for 48 h with LIF. Gene expression was examined by repeated cDNA filter array analysis (n = 5) and key results verified by complementary methods. In LIF-stimulated cultures we observed increased cell area and changes in gene expression. The intracellular signal regulators signal transducer and activator of transcription 3, calcium/calmodulin-dependent protein kinase IV, protein kinase Cdelta and the transcription factor ID1 were upregulated. Adenylyl cyclase V was downregulated. LIF also induced altered expression of tissue inhibitor of metalloproteinase-1. Receptor genes for tumour necrosis factor, interleukin-4, neurotensin and somatostatin were upregulated. Finally, LIF reduced the expression of components in the adenosine triphosphate synthase complex, epidermal fatty acid-binding protein and insulin-like growth factor-binding proteins 1 and 6. Array analysis revealed changes in mRNA levels of several genes not previously associated with activation of the gp130/LIF receptor complex. Our findings indicate a role for LIF in regulation of cardiomyocyte energy metabolism.

Caged ATP光分解に伴う遅筋型筋収縮蛋白の構造変化の超高速時分割2次元X線回折

Caged ATP光分解に伴う遅筋型筋収縮蛋白の構造変化の超高速時分割2次元X線回折

Impact of Mechanical Ventilation on the Developing Airway

After completing this article, readers should be able to: 1. Explain why immature infants are at a greater risk for mechanical ventilation-induced airway damage than are more mature infants. 2. Describe the effect of ventilatory pressures on components of the airway. 3. Delineate how mechanical ventilation disrupts airway mechanics. 4. Characterize how mechanical ventilation affects immature airway smooth muscle. 5. Describe techniques of optimizing ventilation to minimize respiratory damage. Although the air passages take on a mature appearance well before a fetus is viable, they undergo significant maturational changes in late gestation. During development, the airways are more susceptible to damage. In fact, although controversy still surrounds the pathogenesis of bronchopulmonary dysplasia (BPD) and other neonatal airway complications, it appears that the duration and higher pressures of mechanical ventilation, along with the use of oxygen, are related to the development of airway-related problems in preterm infants. As a result, because of their greater need for ventilatory assistance, very preterm infants are at substantially increased risk of airway damage. With recent and continuing advancements in neonatal care, a growing number of immature infants survive premature births. One of the primary hurdles that must be overcome in these infants is respiratory system immaturity. In this context, an understanding of the embryologic development and physiologic maturation of the respiratory system is imperative. The respiratory system can be subdivided grossly into the airways and the lung parenchyma. Developmental changes in the mechanical properties of these two components predispose the immature airway to injury. The immature lung is a relatively noncompliant structure. During neonatal development, lung compliance increases with lung maturity. However, the opposite is true for airways. Immature airways are relatively more compliant than their mature counterparts, with airway maturation resulting in a decrease in airway compliance. This produces an interesting predicament when contemplating the administration of mechanical ventilation …

3L1345 Caged ATP光分解にともなう筋収縮蛋白構造変化の超高速時分割X線回折(10.筋肉(筋蛋白・収縮),一般講演,日本生物物理学会第40回年会)

3L1345 Caged ATP光分解にともなう筋収縮蛋白構造変化の超高速時分割X線回折(10.筋肉(筋蛋白・収縮),一般講演,日本生物物理学会第40回年会)