Distinct forebrain regions define a dichotomous astrocytic profile in multiple system atrophy.

The growing recognition of a dichotomous role of astrocytes in neurodegenerative processes has heightened the need for unraveling distinct astrocytic subtypes in neurological disorders. In multiple system atrophy (MSA), a rare, rapidly progressing atypical Parkinsonian disease characterized by increased astrocyte reactivity. However the specific contribution of astrocyte subtypes to neuropathology remains elusive. Hence, we first set out to profile glial fibrillary acidic protein levels in astrocytes across the human post mortem motor cortex, putamen, and substantia nigra of MSA patients and observed an overall profound astrocytic response. Matching the post mortem human findings, a similar astrocytic phenotype was present in a transgenic MSA mouse model. Notably, MSA mice exhibited a decreased expression of the glutamate transporter 1 and glutamate aspartate transporter in the basal ganglia, but not the motor cortex. We developed an optimized astrocyte isolation protocol based on magnetic-activated cell sorting via ATPase Na+/K+ transporting subunit beta 2 and profiled the transcriptomic landscape of striatal and cortical astrocytes in transgenic MSA mice. The gene expression profile of astrocytes in the motor cortex displayed an anti-inflammatory signature with increased oligodendroglial and pro-myelinogenic expression pattern. In contrast, striatal astrocytes were defined by elevated pro-inflammatory transcripts accompanied by dysregulated genes involved in homeostatic functions for lipid and calcium metabolism. These findings provide new insights into a region-dependent, dichotomous astrocytic response-potentially beneficial in the cortex and harmful in the striatum-in MSA suggesting a differential role of astrocytes in MSA-related neurodegenerative processes.

Morphometric aspects of the jugular foramen in dry skullsof adult individuals in Southern Brazil

The jugular foramen (JF) lies between the occipital bone and the petrosal portion of the temporal bone, andit allows for the passage of important nervous and vascular elements, such as the glossopharyngeal vagusand accessory nerves, and the internal jugular vein. Glomic tumors, schwannomas, metastatic lesions andinfiltrating inflammatory processes are associated with this foramen, which can account for injuries of relatedstructures. Variatons of the JF were already reported regarding shape, size and laterality in one only skull,besides differences related to sex, race and laterality domain, which makes the study of these parameters in thepopulation of southern Brazil significant. Objective: this paper wants to conduct the morphometric analysisof the JF of 111 dry skulls belonging to males and females. Results: the latero-medial the anteroposteriormeasurements showed significant differences when genera were compared and side was compared, respectively.Of the total amount of the investigated skulls, 0.9% showed a complete septum on both sides; 0.9% showedincomplete septum, and 83.8% lacked the septum. The presence of a domed bony roof was noticed in 68.5%of skulls on both sides. Conclusion: the obtained results presented variations regarding some parameterswhen compared to previous studies, thus making it evident the significance of race in the morphometricmeasurements and characteristics of the JF, besides the relevance of studying the kind of impairment whichcan jeopardize important functions, as the cardiac innervation of the vagus nerve.

A Retinal Prosthesis Technology Based on CMOS Microelectronics and Microwire Glass Electrodes.

A very large format neural stimulator device, to be used in future retinal prosthesis experiments, has been designed, fabricated, and tested. The device was designed to be positioned against a human retina for short periods in an operating room environment. Demonstrating a very large format, parallel interface between a 2-D microelectronic stimulator array and neural tissue would be an important step in proving the feasibility of high resolution retinal prosthesis for the blind. The architecture of the test device combines several novel components, including microwire glass, a microelectronic multiplexer, and a microcable connector. The array format is 80 times 40 array pixels with approximately 20 microwire electrodes per pixel. The custom assembly techniques involve indium bump bonding, ribbon bonding, and encapsulation. The design, fabrication, and testing of the device has resolved several important issues regarding the feasibility of high-resolution retinal prosthesis, namely, that the combination of conventional CMOS electronics and microwire glass provides a viable approach for a high resolution retinal prosthesis device. Temperature change from power dissipation within the device and maximum electrical output current levels suggest that the device is acceptable for acute human tests.

The status of structural genomics defined through the analysis of current targets and structures.

Structural genomics--large-scale macromolecular 3-dimenional structure determination--is unique in that major participants report scientific progress on a weekly basis. The target database (TargetDB) maintained by the Protein Data Bank (http://targetdb.pdb.org) reports this progress through the status of each protein sequence (target) under consideration by the major structural genomics centers worldwide. Hence, TargetDB provides a unique opportunity to analyze the potential impact that this major initiative provides to scientists interested in the sequence-structure-function-disease paradigm. Here we report such an analysis with a focus on: (i) temporal characteristics--how is the project doing and what can we expect in the future? (ii) target characteristics--what are the predicted functions of the proteins targeted by structural genomics and how biased is the target set when compared to the PDB and to predictions across complete genomes? (iii) structures solved--what are the characteristics of structures solved thus far and what do they contribute? The analysis required a more extensive database of structure predictions using different methods integrated with data from other sources. This database, associated tools and related data sources are available from http://spam.sdsc.edu.

Normal mode analysis of macromolecular motions in a database framework: developing mode concentration as a useful classifying statistic.

We investigated protein motions using normal modes within a database framework, determining on a large sample the degree to which normal modes anticipate the direction of the observed motion and were useful for motions classification. As a starting point for our analysis, we identified a large number of examples of protein flexibility from a comprehensive set of structural alignments of the proteins in the PDB. Each example consisted of a pair of proteins that were considerably different in structure given their sequence similarity. On each pair, we performed geometric comparisons and adiabatic-mapping interpolations in a high-throughput pipeline, arriving at a final list of 3,814 putative motions and standardized statistics for each. We then computed the normal modes of each motion in this list, determining the linear combination of modes that best approximated the direction of the observed motion. We integrated our new motions and normal mode calculations in the Macromolecular Motions Database, through a new ranking interface at http://molmovdb.org. Based on the normal mode calculations and the interpolations, we identified a new statistic, mode concentration, related to the mathematical concept of information content, which describes the degree to which the direction of the observed motion can be summarized by a few modes. Using this statistic, we were able to determine the fraction of the 3,814 motions where one could anticipate the direction of the actual motion from only a few modes. We also investigated mode concentration in comparison to related statistics on combinations of normal modes and correlated it with quantities characterizing protein flexibility (e.g., maximum backbone displacement or number of mobile atoms). Finally, we evaluated the ability of mode concentration to automatically classify motions into a variety of simple categories (e.g., whether or not they are "fragment-like"), in comparison to motion statistics. This involved the application of decision trees and feature selection (particular machine-learning techniques) to training and testing sets derived from merging the "list" of motions with manually classified ones.

PartsList: a web-based system for dynamically ranking protein folds based on disparate attributes, including whole-genome expression and interaction information.

As the number of protein folds is quite limited, a mode of analysis that will be increasingly common in the future, especially with the advent of structural genomics, is to survey and re-survey the finite parts list of folds from an expanding number of perspectives. We have developed a new resource, called PartsList, that lets one dynamically perform these comparative fold surveys. It is available on the web at http://bioinfo.mbb.yale.edu/partslist and http://www.partslist.org. The system is based on the existing fold classifications and functions as a form of companion annotation for them, providing 'global views' of many already completed fold surveys. The central idea in the system is that of comparison through ranking; PartsList will rank the approximately 420 folds based on more than 180 attributes. These include: (i) occurrence in a number of completely sequenced genomes (e.g. it will show the most common folds in the worm versus yeast); (ii) occurrence in the structure databank (e.g. most common folds in the PDB); (iii) both absolute and relative gene expression information (e.g. most changing folds in expression over the cell cycle); (iv) protein-protein interactions, based on experimental data in yeast and comprehensive PDB surveys (e.g. most interacting fold); (v) sensitivity to inserted transposons; (vi) the number of functions associated with the fold (e.g. most multi-functional folds); (vii) amino acid composition (e.g. most Cys-rich folds); (viii) protein motions (e.g. most mobile folds); and (ix) the level of similarity based on a comprehensive set of structural alignments (e.g. most structurally variable folds). The integration of whole-genome expression and protein-protein interaction data with structural information is a particularly novel feature of our system. We provide three ways of visualizing the rankings: a profiler emphasizing the progression of high and low ranks across many pre-selected attributes, a dynamic comparer for custom comparisons and a numerical rankings correlator. These allow one to directly compare very different attributes of a fold (e.g. expression level, genome occurrence and maximum motion) in the uniform numerical format of ranks. This uniform framework, in turn, highlights the way that the frequency of many of the attributes falls off with approximate power-law behavior (i.e. according to V(-b), for attribute value V and constant exponent b), with a few folds having large values and most having small values.

Visibility of road hazards in thermal, visible, and sensor-fused night-time imagery.

Sensor fusion combines the output of multiple imaging sensors within a single composite display. Ideally, a fused image will retain important spatial information provided by individual input images, and will convey useful spatial or chromatic emergent information derived from the contrast between input images. The present experiment assessed the potential benefits of sensor fusion as a method of enhancing drivers' night-time detection of road hazards. Observers were asked to detect a pedestrian within thermal and visible images of a night-time scene, and within chromatic and achromatic renderings created by sensor fusion of grayscale thermal and visible images. Results indicated that fusion can both improve spatial image content, and can effectively embellish spatial content with emergent chromatic information. The benefits of both sensor fusion and of color rendering, however, were inconsistent, varying substantially with quality of input images submitted for fusion.

Three-dimensional reconstructions of normal and aneurysmatic left ventricles in vivo using transesophageal echocardiography.

OBJECTIVE: To perform three-dimensional surface reconstructions to provide spatial delineations of a normal and an aneurysmatic left ventricle, using transesophageal echocardiography. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Eight patients in cardiogenic shock admitted to the intensive care unit and two patients undergoing surgery with general anesthesia. INTERVENTIONS: Using a multiplane transesophageal echocardiography probe, nine echocardiographic cross-sectional images of the heart at approximately 20 degrees angular increments were obtained from midesophageal level in each patient for three-dimensional surface reconstructions. Multiple determinations of cardiac output using the thermodilution principle were also made in each patient to verify the accuracy of three-dimensional data sets. MEASUREMENTS AND MAIN RESULTS: End-diastolic and end-systolic volumes were determined from three-dimensional data sets using the disc-summation method. Stroke volume was derived as the difference between end-diastolic and end-systolic volumes. Stroke volume was also calculated from thermodilution cardiac output measurements and heart rate. Correlation and limits of agreement between stroke volumes derived by the two methods were determined. Three-dimensional wire-frame models of a normal and an aneurysmatic left ventricle at end-systole were constructed from the nine echocardiographic cross-sectional images. Correlation coefficient between stroke volume derived from three-dimensional data sets using the disc-summation method and that measured by the thermodilution method was 0.91 (p < 0.001). Wire-frame models reveal a normal symmetric cavity and an aneurysmal cavity in sharp relief. CONCLUSIONS: Three-dimensional surface reconstruction can be performed from multiple cross-sectional images obtained using an unmodified commercially available multiplane transesophageal echocardiography probe, to reveal the left ventricular cavity in sharp relief. High correlation between stroke volume calculated from three-dimensional data sets and that measured by the thermodilution method attests to the accuracy of the three-dimensional data sets.

The morph server: a standardized system for analyzing and visualizing macromolecular motions in a database framework.

The number of solved structures of macromolecules that have the same fold and thus exhibit some degree of conformational variability is rapidly increasing. It is consequently advantageous to develop a standardized terminology for describing this variability and automated systems for processing protein structures in different conformations. We have developed such a system as a 'front-end' server to our database of macromolecular motions. Our system attempts to describe a protein motion as a rigid-body rotation of a small 'core' relative to a larger one, using a set of hinges. The motion is placed in a standardized coordinate system so that all statistics between any two motions are directly comparable. We find that while this model can accommodate most protein motions, it cannot accommodate all; the degree to which a motion can be accommodated provides an aid in classifying it. Furthermore, we perform an adiabatic mapping (a restrained interpolation) between every two conformations. This gives some indication of the extent of the energetic barriers that need to be surmounted in the motion, and as a by-product results in a 'morph movie'. We make these movies available over the Web to aid in visualization. Many instances of conformational variability occur between proteins with somewhat different sequences. We can accommodate these differences in a rough fashion, generating an 'evolutionary morph'. Users have already submitted hundreds of examples of protein motions to our server, producing a comprehensive set of statistics. So far the statistics show that the median submitted motion has a rotation of approximately 10 degrees and a maximum Calpha displacement of 17 A. Almost all involve at least one large torsion angle change of >140 degrees. The server is accessible at http://bioinfo.mbb.yale. edu/MolMovDB

An oblique effect of chromatic gratings measured by color-mixture thresholds.

Contrast sensitivity is lower for obliquely oriented achromatic gratings than for vertical or horizontal gratings at high spatial and low temporal frequencies. Although this response is suggestive of mediation by P-pathway cortical correlates, no clear sensory (i.e. class 1) oblique effect has been demonstrated with isoluminant chromatic stimuli. In the present experiment, a two-alternative forced-choice detection task was used to measure observers' sensitivity to spatiotemporal sinusoids varying in orientation and color contrast. A maximum-likelihood method fit ellipses to the thresholds, with the length of each ellipse taken as a measure of chromatic contrast sensitivity at isoluminance, and the width as luminance contrast threshold. A chromatic oblique effect was observed at about 3 cycles deg-1 suggesting an orientation bias within the cortical stream conveying P-cell activity.

Na+ translocation by the NADH:ubiquinone oxidoreductase (complex I) from Klebsiella pneumoniae.

Complex I is the site for electrons entering the respiratory chain and therefore of prime importance for the conservation of cell energy. It is generally accepted that the complex I-catalysed oxidation of NADH by ubiquinone is coupled specifically to proton translocation across the membrane. In variance to this view, we show here that complex I of Klebsiella pneumoniae operates as a primary Na+ pump. Membranes from Klebsiella pneumoniae catalysed Na+-stimulated electron transfer from NADH or deaminoNADH to ubiquinone-1 (0.1-0.2 micromol min-1 mg-1). Upon NADH or deaminoNADH oxidation, Na+ ions were transported into the lumen of inverted membrane vesicles. Rate and extent of Na+ transport were significantly enhanced by the uncoupler carbonylcyanide-m-chlorophenylhydrazone (CCCP) to values of approximately 0.2 micromol min-1 mg-1 protein. This characterizes the responsible enzyme as a primary Na+ pump. The uptake of sodium ions was severely inhibited by the complex I-specific inhibitor rotenone with deaminoNADH or NADH as substrate. N-terminal amino acid sequence analyses of the partially purified Na+-stimulated NADH:ubiquinone oxidoreductase from K. pneumoniae revealed that two polypeptides were highly similar to the NuoF and NuoG subunits from the H+-translocating NADH:ubiquinone oxidoreductases from enterobacteria.

A membrane-bound NAD(P)+-reducing hydrogenase provides reduced pyridine nucleotides during citrate fermentation by Klebsiella pneumoniae.

During anaerobic growth of Klebsiella pneumoniae on citrate, 9.4 mmol of H2/mol of citrate (4-kPa partial pressure) was formed at the end of growth besides acetate, formate, and CO2. Upon addition of NiCl2 (36 microM) to the growth medium, hydrogen formation increased about 36% to 14.8 mmol/mol of citrate (6 kPa), and the cell yield increased about 15%. Cells that had been harvested and washed under anoxic conditions exhibited an H2-dependent formation of NAD(P)H in vivo. The reduction of internal NAD(P)+ was also achieved by the addition of formate. In crude extracts, the H2:NAD+ oxidoreductase activity was 0.13 micromol min-1 mg-1, and 76% of this activity was found in the washed membrane fraction. The highest specific activities of the membrane fraction were observed in 50 mM potassium phosphate, with 1.6 micromol of NADPH formed min-1 mg-1 at pH 7.0 and 1.7 micromol of NADH formed min-1 mg-1 at pH 9.5. In the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the Na+/H+ antiporter monensin, the H2-dependent reduction of NAD+ by membrane vesicles decreased only slightly (about 16%). The NADP+- or NAD+-reducing hydrogenases were solubilized from the membranes with the detergent lauryldimethylamine-N-oxide or Triton X-100. NAD(P)H formation with H2 as electron donor, therefore, does not depend on an energized state of the membrane. It is proposed that hydrogen which is formed by K. pneumoniae during citrate fermentation is recaptured by a novel membrane-bound, oxygen-sensitive H2:NAD(P)+ oxidoreductase that provides reducing equivalents for the synthesis of cell material.

Perceptual ability with real-world nighttime scenes: image-intensified, infrared, and fused-color imagery.

We investigated human perceptual performance allowed by relatively impoverished information conveyed in nighttime natural scenes. We used images of nighttime outdoor scenes rendered in image-intensified low-light visible (i2) sensors, thermal infrared (ir) sensors, and an i2/ir fusion technique with information added. We found that nighttime imagery provides adequate low-level image information for effective perceptual organization on a classification task, but that performance for exemplars within a given object category is dependent on the image type. Overall performance was best with the false-color fused images. This is consistent with the suggestion in the literature that color plays a predominate role in perceptual grouping and segmenting of objects in a scene and supports the suggestion that the addition of color in complex achromatic scenes aids the perceptual organization required for visual search. In the present study, we address the issue of assessment of perceptual performance with alternative night-vision sensors and fusion methods and begin to characterize perceptual organization abilities permitted by the information in relatively impoverished images of complex scenes. Applications of this research include improving night vision, medical, and other devices that use alternative sensors or degraded imagery.

Effects of mission rehearsal simulation on air-to-ground target acquisition.

Traditionally military aviators have prepared for air-to-ground bombing missions with maps and aerial photographs of their targets. Mission rehearsal systems augment these media by allowing pilots to view simulated ingress to their target, as seen from the cockpit perspective. In the present experiment we assessed the benefits of mission rehearsal with a task requiring observers to view recorded approaches to target objects and to detect the target objects as quickly as possible. Results indicated that premission simulations allowed observers to detect target objects at greater stand-off ranges than did study with maps and aerial photographs alone. Actual or potential applications of this research include the deployment of a mission rehearsal system to assist aviators' mission planning.

A database of macromolecular motions.

We describe a database of macromolecular motions meant to be of general use to the structural community. The database, which is accessible on the World Wide Web with an entry point at http://bioinfo.mbb.yale.edu/MolMovDB , attempts to systematize all instances of protein and nucleic acid movement for which there is at least some structural information. At present it contains >120 motions, most of which are of proteins. Protein motions are further classified hierarchically into a limited number of categories, first on the basis of size (distinguishing between fragment, domain and subunit motions) and then on the basis of packing. Our packing classification divides motions into various categories (shear, hinge, other) depending on whether or not they involve sliding over a continuously maintained and tightly packed interface. In addition, the database provides some indication about the evidence behind each motion (i.e. the type of experimental information or whether the motion is inferred based on structural similarity) and attempts to describe many aspects of a motion in terms of a standardized nomenclature (e.g. the maximum rotation, the residue selection of a fixed core, etc.). Currently, we use a standard relational design to implement the database. However, the complexity and heterogeneity of the information kept in the database makes it an ideal application for an object-relational approach, and we are moving it in this direction. Specifically, in terms of storing complex information, the database contains plausible representations for motion pathways, derived from restrained 3D interpolation between known endpoint conformations. These pathways can be viewed in a variety of movie formats, and the database is associated with a server that can automatically generate these movies from submitted coordinates.

Evaluation of regional systolic function in hypertrophic cardiomyopathy and hypertensive heart disease: a three-dimensional echocardiographic study.

Assessment of regional left ventricular (LV) function in patients with asymmetric LV hypertrophy is difficult with two-dimensional echocardiography mainly because of factors such as LV geometry, structure, regional wall stress, and ischemia. Multiplane transesophageal echocardiography with three-dimensional reconstruction of cross-sectional images was used for quantitative evaluation of regional wall thickness and fractional thickening. Fifteen patients (56 +/- 13 years old) with hypertrophic cardiomyopathy (LV ejection fraction 71% +/- 4%), 15 (62 +/- 13 years) with hypertensive heart disease (ejection fraction 66% +/- 8%) and 15 (53 +/- 11 years) healthy control subjects (ejection fraction 61% +/- 5%) were included in the analysis. Regional function was studied in four parallel equidistant short-axis cross sections from base to apex of the reconstructed left ventricle. In 15 degree intervals, 24 wall thickness measurements in each cross section were made at end-diastole and end-systole after endocardial and epicardial border tracing. A total of 192 measurements were obtained in each patient, and absolute wall thickening and fractional thickening were calculated. Absolute and fractional wall thickening showed a significant inverse relation to end-diastolic wall thickness in all heart conditions (r = 0.71, p < 0.0001). Regions of normal wall thickness in diseased patients were not hyperdynamic when compared with normal control subjects. Significant impairment in fractional thickening at identical end-diastolic thickness was observed in the septum compared with the lateral free wall in both hypertrophic cardiomyopathy and hypertensive heart disease. Thus regional systolic function is inversely related to end-diastolic wall thickness. The decrease in regional systolic function with increasing LV hypertrophy was similar in idiopathic and hypertensive cardiomyopathy. In both types of hypertrophy, significant differences in systolic function were observed in septal and lateral wall segments of similar wall thickness. This indicates that factors other than end-diastolic wall thickness influence myocardial thickening in patients with hypertrophy and preserved global function.

Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial.

BACKGROUND: Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness, insomnia, nervousness, nausea, and agitation. We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment, based on fluoxetine's longer half-life. METHODS: In this 4-week study, 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine, sertraline, or paroxetine for 4-24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5-8 days. The Symptom Questionnaire (SQ), the Discontinuation-Emergent Signs and Symptoms checklist, the 28-item Hamilton Depression Rating Scale, and the Montgomery-Asberg Depression Rating Scale were used to assess somatic distress and stability of antidepressant response. RESULTS: Two hundred twenty patients (91%) completed the study. Following interruption of therapy, fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients (p < .001). The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients (p < .001). Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients (p < .001). CONCLUSIONS: Abrupt interruption of antidepressant therapy for 5-8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine.

Three-dimensional echocardiographic determination of left ventricular volumes and function by multiplane transesophageal transducer: dynamic in vitro validation and in vivo comparison with angiography and thermodilution.

The goal of this study was to validate 3-dimensional echocardiography by multiplane transesophageal transducer for the determination of left ventricular volumes and ejection fraction in an in vitro experiment and to compare the method in vivo with biplane angiography and the continuous thermodilution method. In the dynamic in vitro experiment, we scanned rubber balloons in a water tank by using a pulsatile flow model. Twenty-nine measurements of volumes and ejection fractions were performed at increasing heart rates. Three-dimensional echocardiography showed a very high accuracy for volume measurements and ejection fraction calculation (correlation coefficient, standard error of estimate, and mean difference for end-diastolic volume 0.998, 2.3 mL, and 0.1 mL; for end-systolic volume 0.996, 2.7 mL, and 0.5 mL; and for ejection fraction 0.995, 1.0%, and -0.4%, respectively). However, with increasing heart rate there was progressive underestimation of ejection fraction calculation (percent error for heart rate below and above 100 bpm 0.59% and -8.6%, P < .001). In the in vivo study, left ventricular volumes and ejection fraction of 24 patients with symmetric and distorted left ventricular shape were compared with angiography results. There was good agreement for the subgroup of patients with normal left ventricular shape (mean difference +/-95% confidence interval for end-diastolic volume 5.2+/-6.7 mL, P < .05; for end-systolic volume -0.5+/-8.4 mL, P = not significant; for ejection fraction 2.4%+/-7.2%, P = not significant) and significantly more variability in the patients with left ventricular aneurysms (end-diastolic volume 23.1+/-56.4 mL, P < .01; end-systolic volume 5.6+/-41.0 mL, P = not significant; ejection fraction 4.9%+/-16.0%, P < .05). Additionally, in 20 critically ill, ventilated patients, stroke volume and cardiac output measurements were compared with measurement from continuous thermodilution. Stroke volume as well as cardiac output correlated well to thermodilution (r = 0.89 and 0.84, respectively, P < .001), although both parameters were significantly underestimated by 3-dimensional echocardiography (mean difference +/-95% confidence interval = -6.4+/-16.0 mL and -0.6+/-1.6 L/min, respectively, P < .005).

Disturbed intracoronary hemodynamics in myocardial bridging: early normalization by intracoronary stent placement.

BACKGROUND: The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS: In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS: Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.