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PubMed2002

Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices.

Studies were carried out to test the idea that transforming growth factor beta (TGFbeta) stimulated fibroblast contraction of collagen matrices by different mechanisms depending on mechanical loading on the cells and matrix. Under mechanically unloaded conditions (floating matrices), TGFbeta stimulated contraction directly as an agonist and indirectly by preactivating cells to express the myofibroblast phenotype. Increased contraction of floating matrices by preactivated cells appeared to result in part from an autocrine mechanism. Under mechanically loaded conditions (stressed matrices), TGFbeta had no direct agonist effect on contraction. Fibroblasts preactivated to become myofibroblasts showed increased ability to transfer tension to stressed matrices, and tension persisted even after the cells' actin cytoskeleton was disrupted. Our findings are consistent with the idea that fibroblasts activated to become myofibroblasts in vitro have increased contractile activity and indicate that multiple mechanisms that differ depending on mechanical loading on the cells and matrix are involved.

Actins↗

PubMed2000

[Neuropathic pain. The long path from mechanisms to mechanism-based treatment].

Clinical characteristics of neuropathic pain, i.e. pain after nervous system lesions, are burning spontaneous pain, shooting pain attacks and evoked pains. Partly interacting pathophysiological mechanisms at the peripheral and central nervous system may be responsible for initiation and maintenance of chronic neuropathic pain. (1) Peripheral nociceptive fibers can be abnormally sensitized. (2) Central nociceptive second order neurons in the spinal cord dorsal horn can also be sensitized, i.e. they are hyperexcitable and start responding to non-noxious stimuli. (3) Degeneration of nociceptive neurons may trigger anatomical sprouting of low-threshold mechanosensitive terminals to central nociceptive neurons and may subsequently induce synaptic reorganization in the dorsal horn. By this mechanism activity in mechanosensitive neurons may be perceived as painful. (4) Peripheral nerve injury may induce a pathological interaction of the nociceptive system and the efferent sympathetic system. The different mechanisms can operate in concert in a single disease entity (e.g., postherpetic neuralgia) and also in one single patient. Distinct pathophysiological mechanisms lead to specific sensory symptoms (e.g., dynamic mechanical allodynia, cold hyperalgesia). Therefore, a thorough analysis of sensory symptoms may reveal the underlying mechanisms that are mainly active in a particular patient. In the next step novel drugs will be developed that address specifically the relevant mechanism combination. Drug therapies that are available today include NSAIDS, opioids, tricyclic antidepressants, anticonvulsives (carbamazepine, gabapentin), GABA-agonists, Capsaicin and NMDA-antagonists.

Analgesics↗

PubMed2002

Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs.

Carbamazepine (CBZ) and zonisamide (ZNS) are effective antiepileptic drugs (AEDs) for the treatment of epilepsy and mood disorder. One of the mechanisms of action of CBZ and ZNS is inactivation of voltage-gated Na+ channel (VGSC). However, the major mechanism(s) of action of these AEDs is not clear yet. We have been exploring novel targeting mechanisms for the antiepileptic actions of CBZ and ZNS during the past ten years. In this report, we describe our hypothesis regarding the new targeting mechanisms for the antiepileptic action of AEDs. We determined an interaction between these AEDs and inhibitors of both voltage-sensitive Ca2+ channels (VSCCs) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) on neurotransmitter exocytosis using microdialysis. Perfusion with therapeutic concentrations of CBZ and ZNS increased basal neurotransmitter release. This stimulatory action was predominantly inhibited by inhibitors of N-type VSCC and syntaxin. CBZ and ZNS increased Ca2+-evoked release, an action selectively inhibited by inhibitors of N-type VSCC and syntaxin. CBZ and ZNS reduced K+-evoked release, an action predominantly inhibited by inhibitors of P-type VSCCs and synaptobrevin. These actions of CBZ and ZNS on neurotransmitter exocytosis could be observed under the condition of inhibition of VGSC using perfusion with tetrodotoxin. Our findings enhance our understanding of the mechanisms of action of CBZ and ZNS as AEDs, which possibly reduce P-type VSCCs/synaptobrevin-related exocytosis mechanisms during the depolarization stage, and simultaneously enhance N-type VSCCs/syntaxin-related exocytosis mechanisms at the resting stage.

Animals↗

PubMed1998

Effect of mechanical set point of bone cells on mechanical control of trabecular bone architecture.

The architecture of trabecular bone is thought to be controlled by mechanosensitive bone cells, where hormones provide a background for their responses to mechanical signals. It has been suggested that, in osteoporosis, this response is hampered by changed hormonal levels, thereby increasing the mechanical set point of the cells, which would lead to bone loss. We have investigated if a temporary increase of the mechanical set point causes deterioration of trabecular bone architecture, such as seen in osteoporosis. Furthermore, the effects of a changed loading pattern were investigated for the same reason. For this purpose, we used a computer simulation model, which was based on the regulation of bone architecture by mechanosensitive osteocytes. It was found that a temporary shift of the mechanical set point causes no lasting changes in architecture. Although an increase of the mechanical set point induces bone loss, the mechanism of bone loss (trabecular thinning) differs from what is observed in osteoporosis (loss of whole trabeculae). Hence, a change of the mechanical set point alone cannot explain bone loss as seen in osteoporosis. On the other hand, the removal of load components in a particular direction resulted in irreversible loss of whole trabeculae. These results indicate that such temporary changes in loading patterns could be important risk factors for osteoporosis.

Adult↗

PubMed1980

Catalytic mechanism of Escherichia coli alkaline phosphatase: resolution of three variants of the acyl-enzyme mechanism.

Three variants of the classical acyl-enzyme mechanism were compared theoretically with respect to the predicted transient kinetics of substrate hydrolysis by Escherichia coli alkaline phosphatase. In all three, acyl-enzyme hydrolysis was assumed to exist initially primarily as a noncovalent complex with the acid product, inorganic phosphate. In one mechanism, the pre-steady-state rate-controlling step was assumed to be the dissociation of acid product from its initial complex with enzyme. In the other two, pre-steady-state rate control was assigned to an enzyme isomerization occurring before or after substrate binding to free enzyme. Under concentration conditions of excess substrate and acid product, integrated rate laws were used to reject the possibility of pre-steady-state rate control by enzyme isomerization between phosphate dissociation and substrate binding. Whereas this mechanism predicts a pre-steady-state noncompetitive relationship between substrate and acid product, the stopped-flow kinetics of 4-methylumbelliferyl phosphate hydrolysis demonstrates a competitive relationship, consistent with either of the other two mechanisms. Under concentration conditions of stoichiometrically limiting substrate, computer simulations eliminated the possibility of rate control by enzyme isomerization after substrate binding. This mechanism predicts a substrate concentration dependence for the apparent first-order rate constant of substrate hydrolysis which disagrees with previously published data [Halford, S. E. (1971) Biochem. J. 125, 319--327]; the other two mechanisms are consistent with experiment. Comparison of transient kinetic theory and experiment under these two contrasting concentration conditions suggests strongly that the rate-controlling step in phosphate ester hydrolysis by E. coli alkaline phosphate is the dissociation of "sticky" acid product from its noncovalent complex with enzyme. This mechanism explains an anomaly in the stopped-flow kinetic trace, a substoichiometric pre-steady-state burst of alcohol product release.

Alkaline Phosphatase↗

PubMed2005

Conclusive support for mechanical nonsurgical pocket therapy in the treatment of periodontal disease. How effective is mechanical nonsurgical pocket therapy?

DATA SOURCES: Sources of studies were the Cochrane Oral Health Group List of Systematic Reviews in Dentistry, Database of Abstracts of Reviews of Effectiveness, Medline, Embase, and Scisearch. No date or language restriction was imposed. Reference lists of located reviews were checked for additional references. STUDY SELECTION: Twelve reviews addressing the question were included. DATA EXTRACTION AND SYNTHESIS: A narrative appraisal of the reviews was conducted. RESULTS: A number of implications for clinical practice were identified. These are as follows:Initial therapy: In people who have periodontitis, mechanical nonsurgical pocket therapy reduces inflammation and pocket depth and increases clinical attachment level. The magnitude of pocket depth reduction correlates with greater pocket depth before treatment. Nonsurgical mechanical debridement may cause loss of attachment in shallow pockets (</=3 mm). There is no evidence of any difference in efficacy between machine-driven (ultrasonic and sonic) and hand instruments in single-rooted teeth. Machine-driven instruments may be faster than hand instruments. Adjunctive therapies have been developed and investigated but, to date, no therapy exists as a stand alone replacement for mechanical nonsurgical pocket therapy.Maintenance therapy: In periodontal maintenance patients, mechanical debridement reduces inflammation and disturbs the bacterial biofilm, which is thought critical to disease control including prevention of progression. The effect of mechanical nonsurgical pocket therapy on pocket depth reduction and clinical attachment gain in maintenance patients is unclear; maintenance or stability of pocket probing depth and clinical attachment level, however, has been demonstrated and meets the goal of maintenance therapy. There is not clear evidence to form recommendations over time taken, thoroughness and frequency of mechanical debridement for periodontal maintenance care. CONCLUSIONS: Existing evidence in the form of systematic reviews - the highest level of evidence for evaluating a therapy - provides conclusive support for the beneficial effect and efficacy of mechanical nonsurgical pocket therapy in the treatment of periodontal diseases.

Comment↗

PubMed2005

Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients.

BACKGROUND & AIMS: Gastroesophageal reflux is a major problem in mechanically ventilated patients and may lead to pulmonary aspiration and erosive esophagitis. Transient lower esophageal sphincter relaxations are the most common mechanism underlying reflux in nonventilated patients. The mechanisms that underlie reflux in critically ill ventilated patients have not been studied. The aim of this study was to determine the mechanisms underlying gastroesophageal reflux in mechanically ventilated patients in the intensive care unit. METHODS: In 15 mechanically ventilated intensive care unit patients, esophageal motility, pH, and intraluminal impedance (11/15 patients) were recorded for 1 hour before and 5 hours during continuous nasogastric feeding. RESULTS: Basal lower esophageal sphincter pressure was uniformly low (2.2 +/- 0.4 mmHg). The median (interquartile range) acid exposure (pH <4) was 39.4% (0%-100%) fasting and 32% (7.5%-94.2%) fed. Acid reflux occurred in 10 patients, but slow drifts in esophageal pH were also an important contributor to acid exposure. If esophageal pH decreased to pH <4, it tended to remain so for prolonged periods. A total of 46 acid reflux events were identified. Most (55%) occurred because of absent lower esophageal sphincter pressure alone; 45% occurred during straining or coughing. CONCLUSIONS: Gastroesophageal reflux in mechanically ventilated patients is predominantly due to very low or absent lower esophageal sphincter pressure, often with a superimposed cough or strain. These data suggest that measures that increase basal LES pressure may be useful to prevent reflux in ventilated patients.

Adult↗

PubMed2006

Fixed versus free-floating stretcher mechanism in rowing ergometers: mechanical aspects.

The mechanical responses (i.e. external contact forces and external power) of 25 elite rowers to a race-pace rowing protocol were investigated on the traditional fixed stretcher mechanism and the more recently introduced free-floating stretcher mechanism rowing ergometers. Using a Rowperfect rowing ergometer for both conditions, external contact forces at the handle, stretcher and sliding seat, as well as the displacements of the handle and stretcher, were recorded. The external power was calculated as the product of the force and velocity data from both the handle and stretcher. Significant differences (P < 0.05) between the two conditions for each mechanical parameter were observed. The fixed condition showed larger maximum values for forces and external power and average power throughout the rowing cycle. Moreover, rowing with the fixed mechanism generated higher inertial forces during the transition between the propulsion and recovery phases, especially at the catch of the cycle. The results suggest that: (i) muscular coordination may differ according to the stretcher mechanism used, which could have an impact on the physiological adaptations of muscles; and (ii) the free-floating mechanism may induce lower catch and maximum values for net joint forces and net joint moments that could decrease the risk of injury.

Adult↗

PubMed1999

Mechanically elicited nerve root discharge: mechanical irritation and waveform.

OBJECTIVE: Intraoperative monitoring is very important for protecting nerve roots during lumbar surgery for spinal degeneration. Our objective was to evaluate the correlation between the type of mechanical irritation and waveform by mechanically elicited EMGs during the surgery. METHOD: Mechanically elicited EMGs were recorded bilaterally on muscle groups innervated by the lumbar nerve roots in the area of surgery in 24 consecutive patients with lumbar spinal degenerative disease. RESULTS: It was confirmed that surgical irritation produced 3 types of waveforms as discharges from nerve roots; short, waning and continuous discharges. Each waveform was easily elicited mechanically and was sensitively related to the type and strength of mechanical stimulation. CONCLUSION: It was indicated that the mechanical irritation on the root could elicit the nerve root discharge with no post-operative nerve root deficit. It may be useful to monitor the mechanically elicited EMGs during the surgery for spinal degeneration.

Adult↗

PubMed2002

Reversal of atrial mechanical stunning after cardioversion of atrial arrhythmias: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy.

BACKGROUND: Atrial mechanical stunning develops on termination of chronic atrial arrhythmias and is implicated in the genesis of thromboembolic complications after cardioversion. The mechanisms responsible for atrial mechanical stunning are unknown. The effects of atrial rate, isoproterenol, and calcium on atrial mechanical function in patients with atrial stunning have not been evaluated, and it is not known if atrial stunning can be reversed. METHODS AND RESULTS: Thirty-five patients with chronic atrial flutter (AFL) undergoing radiofrequency ablation were studied. Fifteen patients in sinus rhythm undergoing ablation for paroxysmal AFL were studied as control for effects of the procedure. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AFL, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol or calcium. With termination of AFL, LAAEV decreased from 59.0+/-3.7 cm/s to 18.8+/-1.4 cm/s (P<0.0001) and LASEC grade increased from 0.9+/-0.1 to 2.2+/-0.2 (P<0.0001). Pacing increased LAAEV to a maximum of 38.4+/-3.2 cm/s (P<0.0001) and reduced LASEC grade to 1.9+/-0.2 (P=0.005). Isoproterenol and calcium reversed atrial mechanical stunning with LAAEV increasing to 89.3+/-12.6 cm/s (P=0.0007) and 50.2+/-10.5 cm/s (P=0.005), respectively, and LASEC grade decreasing to 0.2+/-0.1 (P=0.001) and 1.4+/-0.2 (P=0.01), respectively. The postpacing pause increased LAAEV to 69.3+/-3.7 cm/s (P<0.0001). No change in LAAEV was observed in the paroxysmal AFL group. CONCLUSION: Atrial mechanical stunning can be reversed by pacing at increased rates and through the administration of isoproterenol or calcium. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium as a result of chronic atrial flutter.

Atrial Flutter↗

PubMed2003

Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy.

BACKGROUND: Atrial mechanical "stunning" develops after cardioversion of atrial fibrillation (AF) and is implicated in the genesis of thromboembolic complications. However, the mechanisms responsible for this phenomenon are poorly understood. Whether atrial mechanical dysfunction caused by AF can be reversed by pacing at increased rates or by pharmacological agents is unknown. METHODS AND RESULTS: Twenty-six patients with AF undergoing cardioversion were dichotomized prospectively on the basis of the duration of arrhythmia as short-duration (1 to 6 months) or long-duration (> or =3 years) AF. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AF, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol. In patients with short-duration AF, LAAEV decreased (42.0+/-2.7 to 18.5+/-2.0 cm/s; P<0.0001) and LASEC increased (0.9+/-0.3 to 2.2+/-0.3; P<0.01) with termination of AF; pacing increased LAAEV (48.3+/-4.1 cm/s; P<0.0001) and decreased LASEC (1.5+/-0.3; P<0.01); isoproterenol increased LAAEV (73.3+/-7.8 cm/s; P<0.0001) and decreased LASEC (0.3+/-0.2; P<0.01); and the postpacing pause increased LAAEV (68.3+/-3.8 cm/s; P<0.0001). In contrast, patients with long-duration AF demonstrated a significantly attenuated response of atrial mechanical function at each time point. With termination of AF, LAAEV decreased (19.1+/-2.6 to 8.2+/-1.0 cm/s; P=0.003) and LASEC increased (2.0+/-0.2 to 3.3+/-0.2; P<0.01); pacing increased LAAEV (18.4+/-2.7 cm/s; P<0.0001) and decreased LASEC (2.3+/-0.2; P<0.01); isoproterenol increased LAAEV (26.1+/-3.9 cm/s; P=NS to equivalent atrial rate) and decreased LASEC (1.0+/-0.3; P<0.01); and the postpacing pause increased LAAEV (27.2+/-2.4 cm/s; P=0.007). CONCLUSIONS: Atrial pacing at increased rates and isoproterenol can reverse atrial mechanical stunning associated with short-duration AF. In contrast, long-duration AF is associated with an attenuated response to these maneuvers. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium caused by AF; however, with longer durations of AF, additional factors may determine atrial mechanical function.

Adrenergic beta-Agonists↗

PubMed2002

Mechanics of elastin: molecular mechanism of biological elasticity and its relationship to contraction.

Description of the mechanics of elastin requires the understanding of two interlinked but distinct physical processes; the development of entropic elastic force and the occurrence of hydrophobic association. Elementary statistical-mechanical analysis of AFM single-chain force-extension data of elastin model molecules identifies damping of internal chain dynamics on extension as a fundamental source of entropic elastic force and eliminates the requirement of random chain networks. For elastin and its models, this simple analysis is substantiated experimentally by the observation of mechanical resonances in the dielectric relaxation and acoustic absorption spectra, and theoretically by the dependence of entropy on frequency of torsion-angle oscillations, and by classical molecular-mechanics and dynamics calculations of relaxed and extended states of the beta-spiral description of the elastin repeat, (GVGVP)n. The role of hydrophobic hydration in the mechanics of elastin becomes apparent under conditions of isometric contraction. During force development at constant length, increase in entropic elastic force resulting from decrease in elastomer entropy occurs under conditions of increase in solvent entropy. This eliminates the solvent entropy change as the entropy change that gives rise to entropic elastic force and couples association of hydrophobic domains to the process. Therefore, association of hydrophobic domains within the elastomer at fixed length stretches interconnecting dynamic chain segments and causes an increase in the entropic elastic force due to the resulting damping of internal chain dynamics. Fundamental to the mechanics of elastin is the inverse temperature transition of hydrophobic association that occurs with development of mechanical resonances within fibrous elastin and polymers of repeat elastin sequences, which, with design of truly minimal changes in sequence, demonstrate energy conversions extant in biology and demonstrate the special capacity of bound phosphates to raise the free energy of hydrophobic association.

Animals↗

PubMed1998

Respiratory oscillation mechanics in infants with bronchiolitis during mechanical ventilation.

The aim of the study was to describe the pattern of respiratory oscillation mechanics and responses to positive end-expiratory pressure (PEEP) in bronchiolitis. Six infants were studied during the course of mechanical ventilation. A 20 Hz sinusoidal pressure variation was applied at the endotracheal tube where flow was measured with a pneumotachograph. Resistance and reactance obtained from the complex pressure-flow ratio were separated during inspiration (R(rs,i); X(rs,i)) and expiration (R(rs,e); X(rs,e)), and the differences between R(rs,i) and R(rs,e) (deltaR(rs)) and X(rs,i) and X(rs,e) (deltaX(rs)) were calculated. The data were corrected for the mechanical characteristics of the endotracheal tube. The measurements were repeated while PEEP was varied between 0 and 8 hPa. Two infants were found to have normal R(rs) and near-zero X(rs) and both parameters exhibited little change within the respiratory cycle or with varying PEEP. Four infants had high R(rs) at zero PEEP. In two, R(rs,i) was markedly elevated (108.5 and 85.2 hPa.s/L, respectively), and X(rs,i) was markedly negative (-25.0 and -22.5 hPa.s/L, respectively) at zero PEEP, while deltaR(rs) and deltaX(rs) were small. R(rs,i) and the absolute value of X(rs,i) decreased with increasing PEEP. This pattern of oscillation mechanics was consistent with low lung volumes and atelectasis, being reversed by increasing PEEP. In the remaining two subjects, R(rs,i) was moderately elevated (57.8 and 53.6 hPa.s/L, respectively) and X(rs,i) moderately negative (-12.5 and -7.7 hPa.s/L, respectively) at zero PEEP. DeltaR(rs) (-59.8 and -56.5 hPa.s/L, respectively) and delta(rs) (28.1 and 48.7 hPa.s/L, respectively) were large, but were dramatically reduced by increasing PEEP. These patterns were consistent with expiratory airflow limitation. Measurements of respiratory impedance are, therefore, informative in regard to the pathophysiological mechanisms occurring in bronchiolitis during mechanical ventilation, and they may be helpful in setting the level and assessing the effect of PEEP.

Airway Resistance↗

PubMed1998

Changes in pulmonary mechanics after fiberoptic bronchoalveolar lavage in mechanically ventilated patients.

OBJECTIVE: We prospectively assessed the impact of bronchoalveolar lavage (BAL) on respiratory mechanics in critically ill, mechanically ventilated patients. STUDY DESIGN: Mechanically ventilated patients underwent BAL of one lung segment using 5 x 20 ml of sterile, physiologic saline with a temperature of 25-28 degrees C. The fractional inspired oxygen was increased to 1.0, but ventilator settings were otherwise left unchanged. Static pulmonary compliance, pulmonary resistance, alveolar ventilation, and serial dead space were measured 60 min and 2 min before and 8, 60, and 180 min after BAL to assess the consequences of the procedure. In addition, blood gases [partial pressure of carbon dioxide in arterial blood (PaCO2) and arterial oxygen tension (PaO2)], hemodynamic variables (heart rate, systolic and diastolic blood pressure), and body temperature were recorded at the same time points. SETTING: Intensive care unit of a university hospital. PATIENTS: 18 consecutive critically ill, mechanically ventilated patients. RESULTS: Pulmonary compliance decreased by 23% (p < 0.05) and pulmonary resistance increased by 22% (p < 0.05) shortly after BAL. The changes in pulmonary compliance and resistance were more than 30% in one third of the patient population. One hour after the procedure, PaO2 was significantly lower and PaCO2 significantly higher than before the procedure. Three hours after the procedure, pulmonary resistance returned to pre-BAL values but compliance remained 10% below baseline values (p < 0.05). CONCLUSION: BAL in mechanically ventilated patients is associated with deterioration of pulmonary mechanics and function.

Adult↗

PubMed2005

Effects of manual hyperinflation and suctioning in respiratory mechanics in mechanically ventilated patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia results from bacterial colonisation of the aerodigestive tract or aspiration of contaminated secretions into the lower airways. As a consequence of infection of the lung parenchyma and alveolitis, accumulation of inflammatory exudates and infiltration of airway mucosa can lead to unfavourable respiratory mechanics in ventilator-associated pneumonia. Tracheal suction is often employed by nursing staff in the management of mechanically ventilated patients with ventilator-associated pneumonia but this technique has the potential to increase respiratory resistance. Manual hyperinflation is used by physiotherapists to improve lung volume and mobilise secretions and has been shown to increase lung compliance. The effect of manual hyperinflation on airway resistance has not been studied. This study aims to demonstrate an additional mechanical benefit to the respiratory system when manual hyperinflation and suction techniques are combined, by comparing the application of manual hyperinflation and suction with suction alone on static lung compliance (C(L)) and inspiratory resistance (R(AW)) in mechanically ventilated patients with ventilator-associated pneumonia. Fifteen adult patients with ventilator-associated pneumonia were recruited and acted as their own controls. Manual hyperinflation followed by suction (manual hyperinflation plus suction) and suction alone were applied consecutively, in random order, on two occasions, four hours apart. Respiratory variables, C(L) and R(AW), were measured five times and the averaged value documented. Data were recorded before, immediately after, and 30 minutes after each intervention protocol. C(L) increased by 22% and R(AW) decreased by 21%, up to 30 minutes after manual hyperinflation plus suction, but not after suction alone. This study suggests that manual hyperinflation in conjunction with suction induces beneficial changes in respiratory mechanics in mechanically ventilated patients with ventilator-associated pneumonia.

Adult↗

PubMed2000

Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways.

Cardiac hypertrophy is a well known response to increased hemodynamic load. Mechanical stress is considered to be the trigger inducing a growth response in the overloaded myocardium. Furthermore, mechanical stress induces the release of growth-promoting factors, such as angiotensin II, endothelin-1, and transforming growth factor-beta, which provide a second line of growth induction. In this review, we will focus on the primary effects of mechanical stress: how mechanical stress may be sensed, and which signal transduction pathways may couple mechanical stress to modulation of gene expression, and to increased protein synthesis. Mechanical stress may be coupled to intracellular signals that are responsible for the hypertrophic response via integrins and the cytoskeleton or via sarcolemmal proteins, such as phospholipases, ion channels and ion exchangers. The signal transduction pathways that may be involved belong to two groups: (1) the mitogen-activated protein kinases (MAPK) pathway; and (2) the janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The MAPK pathway can be subdivided into the extracellular-regulated kinase (ERK), the c-Jun N-terminal kinase (JNK), and the 38-kDa MAPK (p38 MAPK) pathway. Alternatively, the stress signal may be directly submitted to the nucleus via the cytoskeleton without the involvement of signal transduction pathways. Finally, by promoting an increase in intracellular Ca2+ concentration stretch may stimulate the calcium/calmodulin-dependent phosphatase calcineurin, a novel hypertrophic signalling pathway.

Cardiomegaly↗

PubMed2003

A common mechanism for the mechanosensitive regulation of apoptosis in different cell types and for different mechanical stimuli.

In all kinds of tissue cells are influenced by mechanical forces. In vivo fibroblasts are exposed to mechanical tension and endothelial cells are subjected directly to hemodynamic flow. It has been shown that disturbance of the mechanical stimulus leads to apoptosis by induction of an autocrine loop with thrombospondin-1 as ligand and an integrin/integrin associated protein (CD47) complex as receptor. In the present study the nature of the mechanical stimulus has been exchanged for these two cell types. If fibroblasts are subjected to laminar flow apoptosis decreases about 20-fold whereas turbulence leads to an significant increase compared with the static conditions. If endothelial cells grown on thin silicone membranes are exposed to permanent and pulsatile uniaxial strain, the cells are completely devoid of apoptosis. The thrombospondin-1 secretion as well as the expression of CD47 occurs exclusively under mechanical relaxation respectively turbulence. So different types of cells seem to share a common sense deciding whether a mechanical stimulus induces or suppresses apoptosis and use a common molecular machinery for the regulation of the process.

Animals↗

PubMed2005

Integrins beta1, alpha6, and alpha3 contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms.

Mechanical forces regulate lung maturation in the fetus by promoting type II epithelial differentiation. However, the cell surface receptors that transduce these mechanical cues into cellular responses remain largely unknown. When distal lung type II epithelial cells isolated from embryonic day 19 rat fetuses were cultured on flexible plates coated with laminin, fibronectin, vitronectin, collagen, or elastin and exposed to a level of mechanical strain (5%) similar to that observed in utero, transmembrane signaling responses were induced under all conditions, as measured by ERK activation. However, mechanical stress maximally increased expression of the type II cell differentiation marker surfactant protein C when cells were cultured on laminin substrates. Strain-induced alveolar epithelial differentiation was inhibited by interfering with cell binding to laminin using soluble laminin peptides (IKVIV or YIGSR) or blocking antibodies against integrin beta1, alpha3, or alpha6. Additional studies were carried out with substrates coated directly with different nonactivating anti-integrin antibodies. Blocking integrin beta1 and alpha6 binding sites inhibited both cell adhesion and differentiation, whereas inhibition of alpha3 prevented differentiation without altering cell attachment. These data demonstrate that various integrins contribute to mechanical control of type II lung epithelial cell differentiation on laminin substrates. However, they may act via distinct mechanisms, including some that are independent of their cell anchoring role.

Animals↗