Computation of aortic pulse wave velocity and aortic pulse wave velocity and aortic extensibility from pressure gradient measurements.

This study is concerned with the computation of aortic pulse wave velocity based on simultaneous recordings of the aortic pressure gradient and first-time derivative of aortic pressure. These variables were recorded by means of a double-lumen catheter introduced in the aorta of four anesthetized closed chest dogs, and connected to critically damped manometer systems. Results of aortic pulse wave velocity were then compared: (i) to the true phase velocity obtained from spectra of apparent phase velocity, and (ii) to the pulse wave velocity computed from the time shift between maximum slopes of the pressure wave. From the aortic valves to 37 cm down the aortic trunk, pulse wave velocity increased from 410-460 cm/s to approximately 600-800 cm/s. Based on the wave propagation equation presented of Bramwell and Hill (Bramwell, J.C., and Hill, A. V. 1922. Proc. R. Soc. 93, 298-306), volumetric extensibility coefficients were computed from pulse wave velocity data. Results indicated that, from the aortic valves to 37 cm down to the aorta, the mean volumetric extensibility decreased from 0.43-0.56% deltaV/cm H2O to 0.16-0.25% deltaV/cm H2O (1 cm H2O = 94.1 N/m2).     

Oscillation characteristics of biofilm streamers in turbulent flowing water as related to drag and pressure drop

Mixed population biofilms consisting of Pseudomonas aeruginosa, P. fluorescens, and Klebsiella pneumoniae were grown in a flow cell under turbulent conditions with a water flow velocity of 18 cm/s (Reynolds number, Re, =1192). After 7 days the biofilms were patchy and consisted of cell clusters and streamers (filamentous structures attached to the downstream edge of the clusters) separated by interstitial channels. The cell clusters ranged in size from 25 to 750 microm in diameter. The largest clusters were approximately 85 microm thick. The streamers, which were up to 3 mm long, oscillated laterally in the flow. The motion of the streamers was recorded at various flow velocities up to 50.5 cm/s (Re 3351) using confocal scanning laser microscopy. The resulting time traces were evaluated by image analysis and fast Fourier transform analysis (FFT). The amplitude of the motion increased with flow velocity in a sigmoidal shaped curve, reaching a plateau at an average fluid flow velocity of approximately 25 cm/s (Re 1656). The motion of the streamers was possibly limited by the flexibility of the biofilm material. FFT indicated that the frequency of oscillation was directly proportional to the average flow velocity (u(ave)) below 9.5 cm/s (Re 629). At u(ave) greater than 9.5 cm/s, oscillation frequencies were above our measurable frequency range (0.12-6.7 Hz). The oscillation frequency was related to the flow velocity by the Strouhal relationship, suggesting that the oscillations were possibly caused by vortex shedding from the upstream biofilm clusters. A loss coefficient (k) was used to assess the influence of biofilm accumulation on pressure drop. The k across the flow cell colonized with biofilm was 2.2 times greater than the k across a clean flow cell.     

Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m.

Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-level production of human collagen prolyl 4-hydroxylase in Escherichia coli.

The collagen prolyl 4-hydroxylases (C-P4Hs), enzymes residing within the lumen of the endoplasmic reticulum, play a central role in the synthesis of all collagens. The vertebrate enzymes are alpha(2)beta(2) tetramers in which the two catalytic sites are located in the alpha subunits, and protein disulfide isomerase serves as the beta subunit. All attempts to assemble an active C-P4H tetramer from its subunits in in vitro cell-free systems have been unsuccessful, but assembly of a recombinant enzyme has been reported in several cell types by coexpression of the two types of subunit. An active type I C-P4H tetramer was obtained here by periplasmic expression in Escherichia coli strains BL21 and RB791. Further optimization for production by stepwise regulated coexpression of its subunits in the cytoplasm of a thioredoxin reductase and glutathione reductase mutant E. coli strain resulted in large amounts of human type I C-P4H tetramer. The specific activity of the C-P4H tetramer purified from the cytoplasmic expression was within the range of values reported for human type I C-P4H isolated as a nonrecombinant enzyme or produced in the endoplasmic reticulum of insect cells, but the expression level, about 25 mg/l in a fermenter, is about 5-10 times that obtained in insect cells. The enzyme expressed in E. coli differed from those present in vivo and those produced in other hosts in that it lacked the N glycosylation of its alpha subunits, which may be advantageous in crystallization experiments.     

Manipulators inspired by the tongue of the chameleon

Chameleons have developed a specialized ballistic tongue which elongates more than six times its rest length at speeds higher than 3.5 m s(-1) and accelerations 350 m s(-2), with a highly flexible mobile part, and which applies no continuous force during forward motion. These characteristics are possible because this tongue consists of two highly specialized systems, an ejection system for the forward motion and an accordion-like system for the retraction. Four manipulators inspired by the tongue of the chameleon and based on this design have been developed, resulting in three characteristics similar to the tongue of the chameleon: extensibility of the manipulator, flexibility of the mobile part, and absence of continuous force during the forward motion. The first manipulator mimics the basic mechanism of the tongue of the chameleon and reproduced its basic performances. A second manipulator performs a catching function at a speed of 3.5 m s(-1) with an acceleration of 573 m s(-2) while elongating seven times its rest length. The design of this manipulator is such that the dc motor used for retraction applies a torque 25 times its rated torque. Moreover, during the retraction, the mobile part of the manipulator moves due to its own inertia, allowing the dc motor to rotate at full velocity. In another manipulator, the addition of an elastomer in the mobile part allows for control of the retraction velocity. A model for these two manipulators compares well with the experimental data. Finally, the addition of wings on the mobile part allows us to take the advantage of aerodynamic effects, which is unusual for manipulators.     

Effects of prostaglandin E1 on microvascular haemodynamics in progressive systemic sclerosis.

The effects of prostaglandin E1 infusion on nailfold capillary haemodynamics were studied in eight patients with Raynaud''s phenomenon secondary to progressive systemic sclerosis. Using a modified Landis microinjection technique the mean (+/- SEM) transcapillary pressure gradient was increased during and six weeks after infusion by 13.9 +/- 3.2 cm H2O (p less than 0.05) and 5.5 +/- 2.5 cm H2O (p less than 0.05) respectively. Capillary red cell velocity measured in two patients by video television microscopy also increased during and after infusion with prostaglandin E1. Six patients claimed subjective benefit and in three their ulcers healed. These findings support the observed beneficial effect of prostaglandin E1 and suggest that it improves the nutritive capillary circulation by lowering precapillary resistance.     

Ultraweak photon emission in model reactions of the in vitro formation of eumelanins and pheomelanins

Ultraweak luminescence in the spectral region 300-660 nm is generated in the enzymatic (tyrosinase EC.1.14.18.1) and autooxidative polymerization of L-DOPA, 5-S-cysteinyl-DOPA, and L-DOPA + cysteine to eumelanins and pheomelanins, respectively. Using sensitive calibrated single photon counting equipment, the photon emission intensity I and quantum yield phi have been measured: I = 10-100 h nu/s cm3, phi less than or equal to 10(-13) for enzymatic reactions, and I = 500-3000 h nu/s cm3, phi greater than or equal to 5 x 10(-12) for autooxidative ones. 5-S-cysteinyl-DOPA and cysteine exhibit diminished I and phi-values relative to DOPA. Tests with chemiluminogenic probes-luminol and lucigenin, SOD, catalase, peroxidase, H2O2, and spectrophotometric measurements indicate that photon emission is associated with degradative oxidations of melanin subunits by means of active oxygen species as H2O2 and O2.     

Hydrodynamic thickening of lubricating fluid layer beneath sliding mesothelial tissues

The delicate mesothelial surfaces of the pleural space and other serosal cavities slide relative to each, lubricated by pleural fluid. In the absence of breathing motion, differences between lung and chest wall shape could eventually cause the lungs and chest wall to come into contact. Whether sliding motion keeps lungs and chest wall separated by a continuous liquid layer is not known. To explore the effects of hydrodynamic pressures generated by mesothelial sliding, we measured the thickness of the liquid layer beneath the peritoneal surface of a 3-cm disk of rat abdominal wall under a normal stress of 2 cm H2O sliding against a glass plate rotating at 0-1 rev/s. Thickness of the lubricating layer was determined microscopically from the appearance of fluorescent microspheres adherent to the tissue and glass. Usually, fluid thickness near the center of the tissue disk increased with the onset of glass rotation, increasing to 50-200 microm at higher rotation rates, suggesting hydrodynamic pumping. However, thickness changes often differed substantially among tissue samples and between clockwise and counter-clockwise rotation, and sometimes thickness decreased with rotation, suggesting that topographic features of the tissue are important in determining global hydrodynamic effects. We conclude that mesothelial sliding induces local hydrodynamic pressure gradients and global hydrodynamic pumping that typically increases the thickness of the lubricating fluid layer, moving fluid against the global pressure gradient. A similar phenomenon could maintain fluid continuity in the pleural space, reducing frictional force and shear stress during breathing.     

A stochastic model of leukocyte rolling.

Selectin-mediated leukocyte rolling under flow is an important process in leukocyte recruitment during inflammation. The rolling motion of individual cells has been observed to fluctuate randomly both in vivo and in vitro. This paper presents a stochastic model of the micromechanics of cell rolling and provides an analytical method of treating experimental data. For a homogeneous cell population, the velocity distribution is obtained in an analytical form, which is in good agreement with experimentally determined velocity histograms obtained previously. For a heterogeneous cell population, the model provides a simple, analytical method of separating the contributions of temporal fluctuations and population heterogeneity to the variance of measured rolling velocities. The model also links the mean and variance of rolling velocities to the molecular events underlying the observed cellular motion, allowing characterization of the distribution and release rate of the clusters of molecular bonds that tether the cell to substratum. Applying the model to the analysis of data obtained for neutrophils rolling on an E-selectin-coated surface at a wall shear stress of 1.2 dyn/cm2 yields estimations of the average distance between bond clusters (approximately micron) and the average time duration of a bond cluster resisting the applied fluid force (approximately 0.5 s).     

The effect of lobar obstruction on regional perfusion in the intact dog.

The effect of acute obstruction of the right lower lobes (RLL) on the relative perfusion of different lung regions was studied using Xenon-133 in anesthetized artificially ventilated supine dogs. When the RLL were obstructed at functional residual capacity (FRC) and the rest of the lung was inflated to a transpulmonary pressure of 10 or 20 cm H2O (1 cm H2O = 94.1 N/m2), relative perfusion increased within 10 s to the obstructed lobes by 59 and 92%, respectively. The increase was less marked but still present (17 and 42%, respectively) when obstruction was maintained for 15 min, at a time when arterial hypoxemia had occurred. Hence, there was increased perfusion to an obstructed hypoxic region. The perfusion distribution correlated with the difference in alveolar pressure between the obstructed lobes and the unobstructed lobes such that relative perfusion was always increased to the low alveolar pressure region.     

Dynamic modulation of upper airway function during sleep: a novel single-breath method.

To examine the dynamic modulation of upper airway (UA) function during sleep, we devised a novel approach to measuring the critical pressure (Pcrit) within a single breath in tracheostomized sleep apnea patients. We hypothesized that the UA continuously modulates airflow dynamics during transtracheal insufflation. In this study, we examine tidal pressure-flow relationships throughout the respiratory cycle to compare phasic differences in UA collapsibility between closure and reopening. Five apneic subjects (with tracheostomy) were recruited (2 men, 3 women; 18-50 yr; 20-35 kg/m2; apnea-hypopnea index >20) for this polysomnographic study. Outgoing airflow through the UA (face mask pneumotachograph) and tracheal pressure were recorded during brief transtracheal administration of insufflated airflow via a catheter. Pressure-flow relationships were generated from deflation (approaching Pcrit) and inflation (after Pcrit) of the UA during non-rapid eye movement sleep. During each breath, UA function was described by a pressure-flow relationship that defined the collapsibility (Pcrit) and upstream resistance (Rus). UA characteristics were examined in the presence and absence of complete UA occlusion. We demonstrated that Pcrit and Rus changed dynamically throughout the respiratory cycle. The UA closing pressure (4.4 +/- 2.0 cm H2O) was significantly lower than the opening pressure (10.8 +/- 2.4 cm H2O). Rus was higher for deflation (18.1 +/- 2.4 cm H2O x l(-1) x s) than during inflation (7.5 +/- 1.9 cm H2O x l(-1) x s) of the UA. Preventing occlusion decreases UA pressure-flow loop hysteresis by approximately 4 cm H2O. These findings indicate that UA collapsibility varies dynamically throughout the respiratory cycle and that both local mechanical and neuromuscular factors may be responsible for this dynamic modulation of UA function during sleep.     

On defining total lung capacity in the mouse.

Maximal lung volume or total lung capacity in experimental animals is dependent on the pressure to which the lungs are inflated. Although 25-30 cm H2O are nominally used for such inflations, mouse pressure-volume (P-V) curves show little flattening on inflation to those pressures. In the present study, we examined P-V relations and mean alveolar chord length in three strains (C3H/HeJ, A/J, and C57BL/6J) at multiple inflation pressures. Mice were anesthetized, and their lungs were degassed in vivo by absorption of 100% O2. P-V curves were then recorded in situ with increasing peak inflation pressure in 10-cm H2O increments up to 90 cm H2O. Lungs were quickly frozen at specific pressures for morphometric analysis. The inflation limbs never showed the appearance of a plateau, with lung volume increasing 40-60% as inflation pressure was increased from 30 to 60 cm H2O. In contrast, parallel flat deflation limbs were always observed, regardless of the inflation pressure, indicating that the presence of a flat deflation curve cannot be used to justify measurement of total lung capacity in mice. Alveolar size increased monotonically with increasing pressure in all strains, and there was no evidence of irreversible lung damage from these inflations to high pressures. These results suggest that the mouse lung never reaches a maximal volume, even up to nonphysiological pressures >80 cm H2O.     

Determination of erythrocyte transit times through micropores. II-- Influence of experimental and physicochemical factors

A new red blood cell filtration system, termed the Cell Transit Time Analyzer (CTTA), has been developed in order to measure the individual transit times of a large number of cells through cylindrical micropores in special "oligopore" filters: the system operates on the electrical conductometric principle and employs special computer software to provide several measures of the resulting transit time histogram. Using this system with filters having pore diameters of 4.5 or 5.0 cm and length to diameter ratios of 3.0 to 4.7, we have evaluated the effects of several experimental factors on the flow behavior of normal and modified human RBC. Our results indicate : 1) linear PBC pressure - flow behavior over a driving pressure range of 2 to 10.5 cm H2O with zero velocity intercepts at delta P = 0, thus suggesting the Poiseuille - like nature of the flow; 2) resistance to flow or "apparent viscosities" for normal RBC which are between 3.1 to 3.9 cPoise and are independent of driving pressure and pore geometry; 3) increased flow resistance (i.e., increased transit times) for old versus young RBC and for RBC made less deformable by DNP-induced crenation or by heat treatment at 48 degrees C; 4) increased mean transit time and poorer reproducibility when using EDTA rather than heparin as the anticoagulant agent. Further, using mixtures of heat-treated and normal RBC and various percentile values of the transit time histogram. We have been able to demonstrate the presence of sub-populations of rigid cells and thus the value of measurements which allow statistical analyses of RBC populations.     

Effects of selective hypoglossal nerve stimulation on canine upper airway mechanics.

Electrical stimulation of the hypoglossal (XII) nerve has been demonstrated as an effective approach to treating obstructive sleep apnea. The physiological effects of conventional modes of stimulation (i.e., genioglossus activation or whole XII nerve stimulation), however, have yielded inconsistent and only partial alleviations of hypopneic or apneic events. Although selective stimulation of the multifasciculated XII nerve offers many stimulus options, it is not clear how these will functionally affect the upper airway (UAW). To study these effects, animal experiments in eight beagles were performed to investigate changes in the UAW resistance and critical pressure during simulated expiration (n = 4) and inspiration (n = 4). During expiration, nonselective XII nerve stimulation yielded the greatest improvement in UAW resistance (-0.66 +/- 0.11 cm H2O x l(-1) x min(-1)), compared with that for selective activation of the geniohyoid (-0.29 +/- 0.09 cm H2O x l(-1) x min(-1)), genioglossus (-0.31 +/- 0.12 cm H2O x l(-1) x min(-1)), and hyoglossus/styloglossus (0.37 +/- 0.06 cm H2O x l(-1) x min(-1)) muscles. For simulated inspiration, on the other hand, only whole XII nerve stimulation (-0.9 +/- 0.4 cm H2O) and coactivation of the genioglossus + hyoglossus/styloglossus muscles (-1.18 +/- 0.6 cm H2O) produced significant (P < 0.05) improvements in UAW stability (i.e., lowered critical pressure), compared with baseline (-0.52 +/- 0.32 cm H2O). The results of this study suggest that a multicontact nerve electrode can be used to achieve both UAW dilation and patency, comparable to that obtained with nonselective stimulation, by selectively activating the various branches of the XII nerve.     

Formation of the compression zone in a plasma flow generated by a magnetoplasma compressor

Processes occurring in a plasma flow generated by a magnetoplasma compressor (MPC) during the formation of the compression zone are discussed. The paper presents results of measurements of the spatial distribution of the electric current in the plasma flow, the temporal and spatial (along the flow) distributions of the plasma density, and the profiles of the velocity of individual flow layers along the system axis. The spatial distribution of the electromagnetic force in the flow is analyzed. It is shown that the plasma flow is decelerated when approaching the compression zone and reaccelerated after passing it. In this case, the plasma flow velocity decreases from ν = (2–3) × 10⁷ cm/s at the MPC output to ν < 10⁶ cm/s in the region of maximum compression and then again increases to 10⁷ cm/s at a distance of 15–17 cm from the MPC output. In some MPC operating modes, a displacement of the magnetic field from the compression zone and the formation of toroidal electric current vortices in the plasma flow after passing the compression zone were detected.     

Water and deuterium oxide permeability through aquaporin 1: MD predictions and experimental verification

Determining the mechanisms of flux through protein channels requires a combination of structural data, permeability measurement, and molecular dynamics (MD) simulations. To further clarify the mechanism of flux through aquaporin 1 (AQP1), osmotic p(f) (cm(3)/s/pore) and diffusion p(d) (cm(3)/s/pore) permeability coefficients per pore of H(2)O and D(2)O in AQP1 were calculated using MD simulations. We then compared the simulation results with experimental measurements of the osmotic AQP1 permeabilities of H(2)O and D(2)O. In this manner we evaluated the ability of MD simulations to predict actual flux results. For the MD simulations, the force field parameters of the D(2)O model were reparameterized from the TIP3P water model to reproduce the experimentally observed difference in the bulk self diffusion constants of H(2)O vs. D(2)O. Two MD systems (one for each solvent) were constructed, each containing explicit palmitoyl-oleoyl-phosphatidyl-ethanolamine (POPE) phospholipid molecules, solvent, and AQP1. It was found that the calculated value of p(f) for D(2)O is approximately 15% smaller than for H(2)O. Bovine AQP1 was reconstituted into palmitoyl-oleoyl-phosphatidylcholine (POPC) liposomes, and it was found that the measured macroscopic osmotic permeability coefficient P(f) (cm/s) of D(2)O is approximately 21% lower than for H(2)O. The combined computational and experimental results suggest that deuterium oxide permeability through AQP1 is similar to that of water. The slightly lower observed osmotic permeability of D(2)O compared to H(2)O in AQP1 is most likely due to the lower self diffusion constant of D(2)O.     

The effects of nimodipine and L-NAME on coronary flow and oxidative stress parameters in isolated rat heart

The aim of this study was to assess the effects of Ca2+ channel antagonist nimodipine (in concentration which competitive inhibited phosphodiesterase 1--PDE1) on oxidative stress alone or under inhibition of nitric oxide synthase by L-NAME in isolated rat heart. The hearts from male Wistar albino rats (n=18, BM about 200 g, age 8 weeks) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure conditions (CPP, 40-120 cm H2O). The experiments were performed under control conditions, in the presence of Nimodipine (2 microM) or Nimodipine (2 microM) plus L-NAME (30 microM). Coronary flow (CF) varied in the autoregulatory range from 3.7 +/- 0.4 ml/min/g wt at 50 cm H2O to 4.35 +/- 0.79 at 90 cm H2O. Basal nitrite outflow, index of lipid peroxidation (measured as TBARS release) and superoxide anion release (O2-) (at 60 cm H2O) were 0.64 +/- 0.18 nmol/min/g wt, 0.55 +/- 0.13 micromol/min/g wt and 19.72 +/- 3.70 nmol/min/g wt, respectively. Nimodipine induced significant vasodilation at all values of CPP (from 26% at 40 cm H2O to 36% at 120 cm H2O) accompanied with significant decrease of nitrite outflow (from 59% at 40 cm H2O to 40% at 120 cm H2O), significant increase of TBARS above autoregulatory range (about 40%) and significant increase of O2- release (from 186% at 40 cm H2O to 117% at 120 cm H2O). However, perfusion with L-NAME completely reversed the effects of Nimodipine. Nimodipine-induced flow changes were decreased under L-NAME (from 3% at 40 cm H2O to 11% at 120 cm H2O) without changes in the autoregulatory range, accompanied with significantly increased nitrite outflow (from 69% at 40 cm H2O to 36% at 120 cm H2O) and TBARS release (almost 50%), as well as significantly decreased O2- release (from 50% at 40 cm H2O to 43% at 120 cm H20). Our findings show that effect of nimodipine on coronary flow should be significantly influenced by NO, TBARS and O2- release in isolated rat heart.