Direct Mechanical Effects Research Articles

Oxygen Attenuates Atelectasis-induced Injury in the In Vivo Rat Lung

Atelectasis results in impaired compliance and gas exchange and, in extreme cases, increased microvascular permeability, pulmonary hypertension, and right ventricular dysfunction. It is not known whether such atelectasis-induced lung injury is due to the direct mechanical effects of lung volume reduction and alveolar collapse or due to the associated regional lung hypoxia. The authors hypothesized that addition of supplemental oxygen to an atelectasis-prone ventilation strategy would attenuate the pulmonary vascular effects and reduce the local levels of vasoconstrictor eicosanoids. In series 1, anesthetized, atelectasis-prone mechanically ventilated rats were randomly assigned to one of six groups based on the inspired oxygen concentration and ventilated without recruitment. Series 2 was performed to determine the cardiac and pulmonary vascular effects of 21% versus 100% inspired oxygen. In series 3, computed tomography scans were performed after ventilation with a recruitment strategy (21% O2) or no recruitment strategy (21% O2 or 100% O2). In series 4, functional residual capacity was measured in animals where the gas was 21% or 100% O2. The partial pressure of arterial oxygen increased with increasing inspired oxygen, but the alveolar-arterial oxygenation gradient was also greater with higher inspired oxygen. Ventilation with 21% O2 (but not with 100% O2) was associated with progressive pulmonary vascular impedance and increased pulmonary vascular permeability. Prostaglandin F2alpha was increased by mechanical ventilation, especially without supplemental oxygen. Computed tomography scans demonstrated no atelectasis in recruited lungs, and atelectasis in nonrecruited lungs that was greater with supplemental oxygen. Increased atelectasis with 100% O2 (vs. 21% O2) was demonstrated by measurement of functional residual capacity. Although supplemental oxygen worsened atelectasis in this model, it prevented the pathologic effects of atelectasis, including microvascular leak and pulmonary hypertension. Atelectasis-induced lung injury seems to be mediated by hypoxia rather than by the direct mechanical effects of atelectasis.

Third metacarpal bone laterality asymmetry and midshaft dimensions in Thoroughbred racehorses

The aims of this study were to test whether longer third metacarpal (MC3) bones had thicker dorsal cortices in a group of racehorses that were exercising at similar maximum speeds, and to establish if horses with larger differences in length between their right and left MC3 bones showed larger differences in the dorsal cortical thickness between the two limbs. An observational study. Forty Thoroughbred racehorses aged between 2 and 6 years and in training at racing speed at two racing stables were used. Two sets of radiographs of each left and right metacarpus of each horse were measured for bone length and dorsal cortical width according to standardised methods. The dorsal cortex thickness showed a linear relationship with bone length for the range of lengths between 25 and 30 cm for both the right MC3 (R2 = 0.30, P = 0.0003) and the left (R2 = 0.23, P = 0.002). The longer bones had thicker dorsal cortices. When results from the two limbs were combined to test if the difference in length between the right and left MC3 in an individual horse was associated with a thicker dorsal cortex in the longer MC3 there was no consistent relationship (R2 = 0.008, P = 0.58). In this sample of racehorses longer MC3 bones were likely to have been exposed to a greater dorsopalmar bending moment at the mid shaft that was reflected in a thicker dorsal cortex. The lack of a relationship between midshaft thickness and bone length within individual horses suggests that direct mechanical effects of conformation and environment were less important than the individual's level of skill (or the degree of laterality in their movements) developed before their exposure to fast exercise. It is likely that racehorses with longer right MC3 bones were more able to control the loading of the right MC3 than the left during fast exercise.

Effects of tidal volume and respiratory frequency on lung lymph flow

Ventilation (V) increases lung lymph flow (Ql), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min(-1), results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min(-1) and compared with f = 10 min(-1). Three additional groups of six sheep were perfused for 100 min with control V (10 ml/kg, 10 min(-1)). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Ql and vice versa, without corresponding effects on the rate of edema formation. For the same change in V, changing Vt had a greater effect on Ql than changing f. The change in Ql caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Ql caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V altered Ql through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V-induced changes in fluid filtration.

Effects of exercise on plasma catecholamine levels in the toad, Bufo paracnemis: Role of the adrenals and neural control

Resting plasma epinephrine (E) and norepinephrine (N) concentrations for intact toads (Bufo paracnemis) were 5.57+/-1.0 and 0.88+/-0.38 ng/ml, respectively. Exercise induced a significant increase in heart rate, blood pressure and plasma epinephrine (about 4.3 times), whereas norepinephrine remained unchanged. The resting [E]/[N] ratio was 6.3 and increased to 32.9 during exercise. Adrenal denervation did not alter the basal plasma catecholamine or norepinephrine levels after exercise, but prevented the increase in epinephrine during exercise, suggesting that in the intact toad this increase is due to adrenal secretion whereas resting norepinephrine may be liberated by extra-adrenal chromaffin tissues. This also suggests that the adrenal glands can release selectively the two catecholamines. The increases in heart rate and blood pressure in denervated toads were not significantly different from those of intact animals, suggesting that during exercise the sympathetic nerves play the main role in inducing cardiovascular responses. Spinal transection induced a significant increase in basal norepinephrine levels, which remained elevated after exercise. Since spinal toads are unable to perform spontaneous movements it is possible that this increase may be caused by this stressful condition. The increases in heart rate and blood pressure observed in spinal toads during exercise may be due to direct mechanical effects of venous return on the heart.

Pathophysiology of histological changes in early pregnancy loss

An early pregnancy loss (EPL) or first-trimester miscarriage is the most common complication of human reproduction, with an incidence ranging between 50 and 70% of all conceptions. Two-thirds of EPL cases present with a thinner and fragmented trophoblastic shell, and reduced cytotrophoblast invasion of the tips of the spiral arteries. This leads to incomplete plugging during early pregnancy, and premature onset of the maternal circulation throughout the placenta. The excessive entry of maternal blood into the intervillous space has a direct mechanical effect on the villous tissue, and an indirect oxidative stress effect that contributes to cellular dysfunction and/or damage. Correlation of in vivo and in vitro data suggests that overwhelming oxidative stress of the placental tissues represents a common pathophysiological mechanism for the different etiologies of EPL. Autosomal trisomies are the most frequent karyotypic abnormalities found in EPL, but the comparison of data from different cytogenetic studies is difficult because of the lack of clinical information in many cases on maternal age, gestational age, time of fetal demise and the cytogenetic methodology employed. The majority of authors did find a weak association between villous morphologic features and chromosomal abnormalities, with the exception of partial mole triploidy. The comparison of ultrasound findings and placental histological data indicates that villous changes following fetal demise in utero could explain the overall low predictive value of placental histology alone in identifying an aneuploidy or another non-chromosomal etiology. By contrast, the histological features of complete and partial hydatidiform molar EPL are so distinctive that most cases of molar EPL are correctly diagnosed by histological examination alone. Overall, histopathology when correlated with in vivo ultrasound/Doppler has provided novel clues to the pathophysiology of EPL. Prospective studies are needed to evaluate the impact of these findings on routine histopathologic examination in first-trimester miscarriages.

Metal fragment in the temporomandibular joint: a case report

A 56-year-old woman was referred for severe pain and restricted jaw movements with a duration of more than 10 years.In the early 1990s a discectomy on the left side had been performed where the disc was extirpated and replaced with a polymeric implant. Due to infection and pain the implant was removed about 2 months later. In the 10-year period thereafter she suffered pain from the joint, pain from the left ear, tinnitus and restricted mouth opening.A computer tomography scan revealed a foreign body, approximately 4mm in size, situated in the medial part of the glenoid fossa. The metallic foreign body was surgically removed. The pain from her left temporomandibular joint decreased and the mouth opening capacity increased. Patch-testing showed that the patient had a potential for contact allergy to nickel, chromium and cobalt. The foreign body was most probably a fractured tip of a surgical awl. Energy dispersive X-ray analysis revealed that the fragment consisted of iron and chromium. The instrument fragment could have caused the symptoms either by an allergic reaction or a direct mechanical effect.

Heart rate variability and autonomic activity at rest and during exercise in various physiological conditions.

The rhythmic components of heart rate variability (HRV) can be separated and quantitatively assessed by means of power spectral analysis. The powers of high frequency (HF) and low frequency (LF) components of HRV have been shown to estimate cardiac vagal and sympathetic activities. The reliability of these spectral indices, as well as that of LF/HF ratio as a marker of autonomic interaction at rest and during exercise, is briefly reviewed. Modifications in autonomic activities induced by different physiological conditions, e.g. hypoxia exposure, training, and water immersion, have been found in HRV power spectra at rest. The changes in HF and LF powers and in LF/HF ratio observed during exercise have been shown not to reflect the decrease in vagal activity and the activation of sympathetic system occurring at increasing loads. HF peak was recognised in power spectra in the entire range of relative intensity, being responsible for the most part of HR variability at maximal load. LF power did not change during low intensity exercise and decreased to negligible values at medium-high intensity, where sympathetic activity was enhanced. There was no influence from factors such as fitness level, age, hypoxia, and blood distribution. In contrast, a dramatic effect of body position has been suggested by the observation that LF power increased at medium-high intensities when exercising in the supine position. The increased respiratory activity due to exercise would be responsible of HF modulation of HR via a direct mechanical effect. The changes in LF power observed at medium-high intensity might be the expression of the modifications in arterial pressure control mechanisms occurring with exercise. The finding of opposite trends for LF rhythm in supine and sitting exercises suggests that different readjustments might have occurred in relation to different muscular inputs in the two positions.

May open angle glaucomatous disease (OAGD) be considered a neuro-ophthalmological entity?

Open-angle glaucomatous disease (OAGD)-type field loss may run in families with optic neuropathy, ganglion cell damage, and normal hydrodynamics. Recently, patients have been observed with moderately elevated intraocular pressure (IOP) and an absence of functional defects, except for disturbed foveal flicker fusion for the descending green mode, characteristic of a retinal magnoganglion cell impairment. Individuals who received no IOP-lowering treatment developed field defects later on, while those with normal foveal flicker fusion (FFF) tests for the descending green mode did not develop field changes, even without any IOP-lowering treatment. Histopathology of the complete optic pathway of advanced OAGD revealed pronounced but not total retinal ganglion cell loss. At the level of the simple ascending atrophic optic nerve, however, axons were observed with preserved myelin sheaths, proof that not all ganglion cells were lost, whereas the primary cause of total ascending optic atrophy can only be explained in OAGD by transsection of laminar optic nerve axons, due to impaired capillary output. Thus, changes in FFF frequencies appear to be the earliest functional hallmark in OAGD, while ophthalmoscopy under red-free light reveals loss of peripapillary axons as the first anatomic hallmark of OAGD optic neuropathy. Neuroprotective treatment has been reported to be beneficial. Faulty control of apoptosis (susceptibility factor) in some retinal ganglion cells before clinical symptoms develop may be the cause. The loss of ganglion cells occurs more rapidly in the presence of a relatively high IOP. Ultrastructural changes in guinea pig optic nerves have been reported after the experimental acute increase of IOP. In order to determine if the damage to some ganglion cells was due to the direct effect of the increased IOP or to a vascular stealing phenomenon, we repeated the experiments in birds (chickens) of which it is known that there is no vascular supply to the retinal ganglion cells. Progressively elevated IOP of different duration resulted in the appearance of an apoptotic look of some ganglion cells; when the duration of IOP elevation was longer, more cells were damaged. Additionally, a necrotic look appeared, while axons at the laminar level were rather mildly affected. Therefore, a different sensitivity of ganglion cells to the direct mechanical effect of IOP elevation appears to be likely. Besides the impairment of the choroidoscleral outflow damaging the axons, a more seriously damaging effect of raised IOP to some ganglion cells has to be considered in humans expressing the apoptotic p 53 gene before clinical symptoms develop.The ascending mode may be preponderant, acting simultaneously with the descending mode, but it must be emphasized that primary impairment of some retinal ganglion cells may be most probable.

Augmentation of ultrasound-induced clot disruption by nongas-filled microparticles.

The augmentation of ultrasound-induced clot disruption by echocardiographic contrast microbubbles may be a direct mechanical erosive effect of the clot by the microparticles. To further assess this hypothesis, we evaluated the rate and extent of clot disruption by using external ultrasound and nongas-filled microparticles (HAEMACCEL and HAES). Human blood clots were used in this in vitro study. The percent clot reduction using the combination of ultrasound and microparticles was dose dependent and significantly higher than that with microparticles alone.

Acute Effects of Peritoneal Dialysis on Hemodynamics

To investigate the acute hemodynamic effects of peritoneal dialysis (PD) using the noninvasive Portapres technique [TNO Biomedical Instrumentation (TNO BMI); Amsterdam, The Netherlands]. Blood pressure was measured in 21 consecutive patients on continuous ambulatory PD during a standard peritoneal permeability analysis (SPA). Blood pressure, stroke volume, cardiac output, and total peripheral resistance were recorded and calculated using continuous finger pressure recordings with Portapres and Modelflow software (TNO BMI). The SPA consists of four phases: (1) drainage of night dwell dialysate, (2) instillation of a rinsing solution (1.36% glucose), (3) drainage of rinsing solution, and (4) instillation of the test solution (3.86% glucose to which dextran 70 has been added). Both systolic blood pressure (SBP) (7 +/- 9 mmHg, p < 0.005) and diastolic blood pressure (DBP) (5 +/- 6 mmHg, p < 0.01) increased during phase 2. Systolic BP and DBP increased further during phase 4 (SBP 8 +/- 14 mmHg, p < 0.05; DBP 6 +/- 8 mmHg, p < 0.005). These BP increases were caused by a rise in total peripheral resistance of 10% +/- 18% (p< 0.05) during phase 1, and 15% +/- 21% (p < 0.005) during phase 2. Instillation and dwell of a dialysis solution during PD causes a rise in blood pressure. This is caused by an increase in total peripheral resistance. Factors influencing total peripheral resistance could be a direct mechanical effect of dialysate on mesenteric resistance vessels or a temperature-related effect.

Diving and marine medicine review part II: diving diseases.

Diving is a high-risk sport. There are approximately between 1 to 3 million recreational scuba divers in the USA (with over a quarter-million learning scuba annually); there are about 1 million in Europe and over 50,000 in the United Kingdom. In this population 3-9 deaths/100,000 occur annually in the US alone, and those surviving diving injuries far exceeds this. Diving morbidity can be from near-drowning, from gas bubbles, from barotrauma or from environmental hazards. In reality, the most common cause of death in divers is drowning (60%), followed by pulmonary-related illnesses. The mean number of annual diving fatalities in the USA from 1970 to 1993 was 103.5 (sd 24.0) and the median was 106. This article will focus primarily upon pressure effects on the health of a diver. There are two principle ways pressure can affect us: by direct mechanical effects and by changing the partial pressures of inspired gases. Dysbarism is a general term used to describe pathology from altered environmental pressure, and has two main forms: barotrauma from the uncontrolled expansion of gas within gas-filled body compartments and decompression sickness from too rapid a return to atmospheric pressure after breathing air under increased pressures. Greater than 90% of the human body is either water or bone, which is incompressible; the areas directly affected by pressure changes thus are those that are filled with air or gas. These sites include the middle ear, the eustachian tube, the sinuses, the thorax, and the gastrointestinal tract. Air in these cavities is compressed when the ambient pressure rises because the pressure of inhaled air must equilibrate with the ambient pressure.

Sialadenopathy with the Laryngeal Mask Airway

To the Editor: Hooda and Gupta [1] reported the first case of acute transient sialadenopathy associated with the laryngeal mask airway (LMA). In their Discussion, they state that there was no clinical evidence of malpositioning to account for this complication, but the Figure thatthey provide suggests otherwise and hints at a possible etiology. Their Figure 1shows that the LMA tube was not in the midline and was probably protruding excessively from the mouth. This suggests that the cuff was either rotated or subject to a rotational force, and either not inserted deeply enough or overinflated. The authors did not state the volume used to inflate the cuff. Although ease of manual ventilation is associated with correct LMA placement [2], adequate function is still possible when the LMA is grossly malpositioned [3]. Figure 1also shows that the tube is being pulled cranially by the anesthesia breathing system against its natural caudal curve. Such a force would tend to displace the cuff from the hypopharynx and lever it anteriorly with the teeth functioning as a fulcrum. This would increase the pressure exerted by the cuff against anterior structures, such as the base of tongue. Finally, indirect evidence that sialadenopathy is related to malposition is that the mean mucosal pressure exerted by the LMA cuff at the base of the tongue is only 27 cm H2 O when the device is inserted/fixed correctly and fully inflated [4]. It is unlikely that such low pressures could cause sialadenopathy by a direct mechanical effect. We conclude that the combination of malpositioning and additional anterior pressure might be sufficient to produce sialadenopathy in some patients. The risk of this complication should be minimized if the LMA is inserted, fixed, and inflated correctly [5]. J. Brimacombe, MB ChB, FRCA, MD University of Queensland; Cairns Base Hospital, Australia C. Keller, MD University of Innsbruck, Innsbruck, Austria

Changes in pulmonary vascular resistance in response to partial liquid ventilation

Background/Purpose: Partial liquid ventilation (PLV) with perfluorocarbons decreases pulmonary vascular resistance (PVR) in injured piglet lungs without supplemental oxygen. These PVR changes may result either from direct mechanical effects or improved arterial oxygenation. In an uninjured hypoxic model of elevated PVR the authors asked the following questions: (1) Does prophylactic or therapeutic PLV ameliorate the PVR response to hypoxia? (2) Do prophylactic and therapeutic PLV have different PVR effects? (3) Does supplemental oxygen modify PVR response to PLV? Methods: Piglet (3 to 4 kg) lungs were isolated in situ without ischemia, hypoxia, or reperfusion injury. Pulmonary artery (PA) and left atrial (LA) cannulae were attached to a bloodprimed extracorporeal membrane oxygenation (ECMO) perfusion circuit with a flow (Q PA) of 80 mL/kg/min. Pressure-limited, volume-cycled ventilation (PIP < 25 mm Hg, T v = 15 mL/kg) was initiated. PLV with perfluorodecalin (15 mL/kg) was administered endotracheally. Continuously monitored blood gas parameters allowed airway and extracorporeal adjustment of Fio 2 to produce a Po 2 appropriate to the experimental phase. PVR was calculated as ( P PA−P LA Q PA ). After a stable 30-minute normoxic baseline, animals were assigned randomly to three groups. In group I, control (n = 7), PVR was measured for 150 minutes in hypoxic lungs ( Fio 2 = 0.07, P PAo 2 = 40 mm Hg, S PAo 2 = 70%). In group II, prophylactic (n = 8), PLV was administered, followed by 90 minutes of hypoxia, and 60 minutes of oxygen recovery ( Fio 2 = 0.21 – 0.30, P PAo 2 > 100 mm Hg, S PAo 2 = 100%). In group III, therapeutic (n = 8), after 30 hypoxic minutes, PLV was administered and maintained for 90 minutes, followed by a 60-minute oxygen recovery phase. Results were expressed as mean ± SEM. Statistical analysis of groups was performed by repeated measures of analysis of variance (ANOVA) and Tukey correction. Results: In group I normoxic gas-ventilated PVR was 174 ± 12 mm Hg/L/kg/min. After 90 hypoxic minutes PVR was 318 ± 37 ( P < .01 v baseline). In group II baseline PVR was 183 ± 14. PVR after 30 normoxic minutes of PLV was 199 ± 14 ( P = ns v baseline). After 90 hypoxic minutes, PVR was 350 ± 31 ( P < .01 v baseline, and PLV alone) followed by a decrease to 192 ± 19 after 60 minutes of oxygen recovery ( P = ns v baseline or PLV alone). In group III baseline PVR was 160 ± 17 and 325 ± 29 after 30 hypoxic minutes. After 90 hypoxic minutes of PLV, PVR was 366 ± 22 ( P = ns v hypoxia control, P < .01 v normoxic baseline). PVR recovered to 189 ± 19 after 60 minutes of oxygen recovery ( P = ns v baseline). Conclusions: Prophylactic/therapeutic PLV had no effect on hypoxia-induced increases in PVR and did not differ from each other. Although PLV alone decreases PVR in the injured lung without supplemental oxygen, elevated PVR associated with hypoxia was ameliorated only by supplemental oxygen in the liquid ventilated lung.

Direct mechanical effects of wind on crops

This review describes those mechanisms by which wind directly affects crop growth rates and hence yields. Wind-induced plant movement is capable of altering growth rates and leaf morphology, although this is unlikely to be a major cause of growth differences between sheltered and unsheltered crops grown outdoors. The wind's force can tear leaves or strip them from the plant. Dense plant canopies may suffer abrasion through intermittent or constant rubbing. Soil particles lifted into suspension by the wind have the potential to abrade and damage plant tissue. The wind's force can physically knock plants over, making crops difficult to harvest. Each of these mechanisms operates at a particular time of the growing season. Recovery, and hence final yield, depends on the growth stage and soil/plant moisture status when the damage occurred, the particular species and variety as well as the preceding and subsequent weather. The fact that damage effects are so dependent on the crop and the past weather makes modelling and any simple synthesis of direct wind effects difficult. The most common forms of damage likely in Australia's agricultural regions are from sandblasting and lodging. These damage events will be intermittent – their frequency depending on the local climate. Leaf tearing is likely in broad-leafed horticultural crops, and growth effects are also likely in any windy location. It is not possible to predict what the impact of this damage, and other direct effects, will be on final yields, Based on the results in the literature, protection from damage offered by windbreaks may have as large an effect on yields as incremental microclimate benefits.

Vibrational force alters mRNA expression in osteoblasts

Serum-deprived mouse osteoblastic (MC3T3E1) cells were subjected to a vibrational force modeled by NASA to simulate a space shuttle launch (7.83 G rms). The mRNA levels for eight genes were investigated to determine the effect of vibrational force on mRNA expression. The mRNA levels of two growth-related protooncogenes, c-fos and c-myc, were up-regulated significantly within 30 min after vibration, whereas those of osteocalcin as well as transforming growth factor-beta1 were decreased significantly within 3 h after vibration. No changes were detected in the levels of beta-actin, histone H4, or cytoplasmic phospholipase A2 after vibration. No basal levels of cyclooxygenase-2 expression were detected. In addition, the extracellular concentrations of prostaglandin E2 (PGE2), a potent autocrine/paracrine growth factor in bone, were not significantly altered after vibration most likely due to the serum deprivation state of the osteoblasts. In comparison with the gravitational launch profile, vibrational-induced changes in gene expression were greater both in magnitude and number of genes activated. Taken together, these data suggest that the changes in mRNA expression are due to a direct mechanical effect of the vibrational force on the osteoblast cells and not to changes in the local PGE2 concentrations. The finding that launch forces induce gene expression is of utmost importance since many of the biological experiments do not dampen vibrational loads on experimental samples. This lack of dampening of vibrational forces may partially explain why 1-G onboard controls sometimes do not reflect 1-G ground controls. These data may also suggest that scientists use extra ground controls that are exposed to launch forces, have these forces dampened on launched samples, or use facilities such as Biorack that provide an onboard 1-G centrufuge in order to control for space shuttle launch forces.

On the Origin of the Bolivian High and Related Circulation Features of the South American Climate

Abstract The climatological structure in the upper-tropospheric summertime circulation over South America is diagnosed using a GCM (with and without South American topography), a linear model, and observational data. Emphasis is placed on understanding the origin of observed features such as the Bolivian high and the accompanying “Nordeste low” to the east. Results from the linear model indicate that these two features are generated in response to precipitation over the Amazon basin, central Andes, and South Atlantic convergence zone, with African precipitation also playing a crucial role in the formation of the Nordeste low. The direct mechanical and sensible heating effects of the Andes are minimal, acting only to induce a weak lee trough in midlatitudes and a shallow monsoonal circulation over the central Andes. In the GCM, the effects of the Andes include a strengthening of the Bolivian high and northward shift of the Nordeste low, primarily through changes in the precipitation field. The position of ...

Mechanical and electrical interactions in bone remodeling

The natural remodeling and adaptation of skeletal tissues in response to mechanical loading is a classic example of physical regulation in biology. It is largely because it involves forces that do not seem to fit into the familiar schemes of biochemical controls that bone adaptation mechanisms have intrigued us for at least a century. The effect of electromagnetic fields on organisms is another example of this, and the two have become linked in an attempt to explain bone remodeling ("Yasuda's hypothesis"). This paper re-examines the roles of endogenous and exogenous electromagnetic fields in the response of bone to mechanical forces. A series of experiments is reviewed in which mechanical and electrical stimuli were applied to implants in the medullary canal of rabbit long bones. The results suggest that endogenously generated electrical currents are not required to initiate mechanically stimulated bone formation, but that direct mechanical effects on bone cells is the more likely scenario. Based on this and other evidence from the literature, it is suggested that when exogenous electromagnetic stimuli are applied, bone cells respond by modulating the activity of more primary activators such as hormones, growth factors, cytokines, and mechanical forces.

System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade.

We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

Effects of Simulated High Altitude on Patients Who Have Had Radial Keratotomy

Previous studies documented diurnal myopic shifts in patients who have had radial keratotomy (RK). Recently, hyperopic shifts in these patients exposed to high altitude have been reported. A direct mechanical effect of reduced barometric pressure on surgically altered corneas has been theorized to cause this hyperopic shift. Another hypothesis implicates the effect of hypobaric hypoxia on the RK incisions. The authors examined the effect of a 6-hour exposure to decreased barometric pressure on 14 normal and 18 RK corneas. Cycloplegic refraction, keratometry, corneal pachymetry, and tonometry were performed on seven control subjects and nine patients who have had RK. Measurements were obtained over 8 hours at sea level on day 1 of the study. Measurements were repeated on day 2 which included a 6-hour exposure to 12,000 feet simulated altitude in a hypobaric chamber. Results were compared between subjects and control subjects to determine the effect of a 6-hour exposure to decreased barometric pressure. There was no statistically significant difference in refraction or keratometry readings between control subjects and subjects who have had RK. Central corneal thickness decreased in the afternoon in RK eyes compared with control eyes. There was no clinically significant difference in intraocular pressure between subjects who have had RK and control subjects. A measurable hyperopic shift in RK corneas exposed to high altitude requires more than 6 hours to develop. A direct effect on corneal shape due to barometric pressure alone should produce a sudden change in refractive error. This study supports the hypothesis that a slow metabolic process is responsible for the previously documented hyperopic shifts induced by altitude. However, a barometric pressure effect requiring more than 6 hours to occur cannot be ruled out with the methodology used in this study.

Osmotic dilution stimulates axonal outgrowth by making axons more sensitive to tension

Mechanical tension is a potent stimulator of axonal growth rate, which is also stimulated by osmotic dilution. We wished to determine the relationship, if any, between osmotic stimulation and tensile regulation of axonal growth. We used calibrated glass needles to apply constant force to elongate axons of cultured chick sensory neurons. We find that a neurite being pulled at a constant force will grow 50–300% faster following a 50% dilution of inorganic ions in the culture medium. That is, osmotic dilution appears to cause axons to increase their sensitivity to applied tensions. Experimental interventions suggest that this effect is not mediated by dilution of extracellular calcium, or to osmotic stimulation of adenylate cyclase, or to osmotic stimulation of mechanosensitive ion channels. Rather, experiments measuring the static tension normally borne by neurites suggest a direct mechanical effect on the cytoskeletal proteins of the neurite shaft. Our results are consistent with a formal thermodynamic model for axonal growth in which removing a compressive load on axonal microtubules promotes their assembly, thus promoting axonal elongation.