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At least 415 records · Page 23Linked to original sources
PubMed2001

Spatial heterogeneity of calcium transient alternans during the early phase of myocardial ischemia in the blood-perfused rabbit heart.

BACKGROUND: Optical mapping of cytosolic calcium transients in intact mammalian hearts is now possible using long-wavelength [Ca(2+)](i) indicators. We propose that beat-to-beat [Ca(2+)](i) transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane currents. METHODS AND RESULTS: To test this hypothesis, isolated rabbit hearts were loaded with the fluorescent [Ca(2+)](i) indicator, rhod-2 AM, and imaged at 300 frames/sec during blood-perfused ischemic trials. High-quality [Ca(2+)](i) transients were recorded in each of 8 hearts.[Ca(2+)](i) transient alternans was never present in control records but occurred in each of the hearts during ischemia, with onset after 2 to 4 minutes. Alternans was confined to circumscribed regions of the heart surface 5 to 15 mm across. Multiple regions of alternans were found in most hearts, and regions that were out of phase with one another were found in 6 hearts. Quantitative maps of alternans were constructed by calculating an alternans ratio. This ratio behaved as a continuous variable that reached a maximum value in the center of the regions with alternans. CONCLUSIONS: These results demonstrate marked spatial heterogeneity of the [Ca(2+)](i) transient during the early phase of ischemia, which could produce electrical instability and arrhythmias in large mammalian hearts.

Animals↗
PubMed2005

Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium.

BACKGROUND: Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The specific I(Kr) blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral re-entry had never been investigated. METHODS AND RESULTS: A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system. Nifekakant (0.5 micromol/L) caused significant prolongation of action potential duration (APD) and LID (3 micromol/L) attenuated the APD prolongation without affecting the conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT. Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering). These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID. CONCLUSIONS: The effects of NIF on the spiral excitations are reversed by LID. This interaction should be taken into account when these drugs are used in combination to treat VT/VF.

Animals↗
PubMed1994

Biostereometric measurement of oral tumour growth. Description of the technique and case report.

Following radiotherapy, it may be difficult to determine clinically whether tumour regression, stabilization or growth has occurred. Traditional diagnostic imaging may not be possible due to the small size of the tumour and the proximity of metallic restorations. A case of squamous cell carcinoma of the mandibular alveolar process in which these problems arose is presented. A computer-assisted biostereometric technique was used to identify volumetric change of the tumour. Polyvinylsiloxane impressions were obtained to record the anatomy of the tumour site. From these, stone models were made at four and eight weeks following radiotherapy. Using optical mapping techniques, tumour growth was demonstrated which was not evident on follow-up examinations. The methodolgy of biostereometry is presented and its advantages and potential applications are discussed.

Carcinoma, Squamous Cell↗
PubMed2000

Covariant discretization of axis-symmetric linear optical systems.

We propose a discretization strategy for systems with axial symmetry. This strategy replaces the continuous position coordinates by a discrete set of sensor points, on which the discrete wave fields transform covariantly with the group of 2 x 2 symplectic matrices. We examine polar arrays of sensors (i.e., numbered by radius and angle) and find the complete, orthonormal sets of discrete-waveguide Meixner functions; when the sensors come closer together, these tend to the Laguerre eigenmodes of the continuous waveguide. In particular, the fractional Hankel transforms are discretized in order to define the fractional Hankel-Meixner transforms and similarly for all axis-symmetric linear optical maps. Coherent states appear in the discrete cylindrical waveguide. Covariant discretization leads to the same Wigner phase-space function for both the discrete and the continuum cases. This reinforces a Lie-theoretical model for the phase space of discrete systems.

Journal Article↗
PubMed2006

Calcium instabilities in mammalian cardiomyocyte networks.

The degeneration of a regular heart rhythm into fibrillation (a chaotic or chaos-like sequence) can proceed via several classical routes described by nonlinear dynamics: period-doubling, quasiperiodicity, or intermittency. In this study, we experimentally examine one aspect of cardiac excitation dynamics, the long-term evolution of intracellular calcium signals in cultured cardiomyocyte networks subjected to increasingly faster pacing rates via field stimulation. In this spatially extended system, we observed alternans and higher-order periodicities, extra beats, and skipped beats or blocks. Calcium instabilities evolved nonmonotonically with the prevalence of phase-locking or Wenckebach rhythm, low-frequency magnitude modulations (signature of quasiperiodicity), and switches between patterns with occasional bursts (signature of intermittency), but period-doubling bifurcations were rare. Six ventricular-fibrillation-resembling episodes were pace-induced, for which significantly higher complexity was confirmed by approximate entropy calculations. The progressive destabilization of the heart rhythm by coexistent frequencies, seen in this study, can be related to theoretically predicted competition of control variables (voltage and calcium) at the single-cell level, or to competition of excitation and recovery at the cell network level. Optical maps of the response revealed multiple local spatiotemporal patterns, and the emergence of longer-period global rhythms as a result of wavebreak-induced reentries.

Action Potentials↗
PubMed2005

Molecular applications for identifying microbial pathogens in the post-9/11 era.

Rapid advances in molecular and optical technologies over the past 10 years have dramatically impacted the way biologic research is conducted today. Examples include microarrays, capillary sequencing, optical mapping and real-time sequencing (Pyrosequencing). These technologies are capable of rapidly delivering massive amounts of genetic information and are becoming routine mainstays of many laboratories. Fortunately, advances in scientific computing have provided the enormous computing power necessary to analyze these enormous data sets. The application of molecular technologies should prove useful to the burgeoning field of microbial forensics. In the post-9/11 era, when securing America's food supply is a major endeavor, the need for rapid identification of microbes that accidentally or intentionally find their way into foods is apparent. The principle that distinguishes a microbial forensic investigation from a molecular epidemiology study is that a biocrime has been committed. If proper attribution is to be attained, a link must be made between a particular microbe in the food and the perpetrator who placed it there. Therefore, the techniques used must be able to discriminate individual isolates of a particular microbe. A battery of techniques in development for distinguishing individual isolates of particular foodborne pathogens is discussed.

Bioterrorism↗
PubMed2006

Cardiac conduction through engineered tissue.

In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal's natural life. Perfusion of hearts with fluorescently labeled lec-tin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding re-cipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy.

Animals↗
PubMed2001

Roles of line stimulation-induced virtual electrodes and action potential prolongation in arrhythmic propagation.

INTRODUCTION: Line stimulation across fibers generates a virtual electrode (VE) pattern that consists of adjacent +Vm and -Vm regions. In this study, we evaluated Vm at the break of line stimulation pulses to determine where arrhythmias arise and their propagation direction relative to +Vm and -Vm regions. METHODS AND RESULTS: We optically mapped the anterior left ventricular epicardium of isolated rabbit hearts (n = 9). Monophasic line stimuli were applied across fibers at various coupling intervals. In 18 of 24 break arrhythmias, i.e., arrhythmias in which propagation occurred after the break but < or = 30 msec postshock, excitation propagated from the border between +Vm and -Vm regions toward the -Vm region (P < 0.05) for either shock polarity, even though locations of positive and negative Vm changed with shock polarity. In 13 of 18 make arrhythmias, i.e., arrhythmias in which propagation occurred before the break, the excitation propagated from the center of the +Vm region toward the -Vm regions (P < 0.05). For late arrhythmias, i.e., arrhythmias in which propagation was found >30 msec postshock, propagation was reversed, i.e., toward the +Vm region (P < 0.01), which was where the positive VE produced action potential prolongation. CONCLUSION: The propagation of break, make, and late arrhythmias is spatially related to VEs. The different direction of propagation of late arrhythmias relative to the VEs is explained by the delayed recovery of Vm due to VE-induced action potential prolongation.

Action Potentials↗
PubMed2003

Developmental transitions in cardiac conduction.

The proper sequence of electrical activation of the mature four-chambered heart requires specialized conduction pathways including the His-Purkinje system and a nearly complete separation of the atrial and ventricular myocardium. We tracked the emergence of the structure of the mature His-Purkinje system in the developing chicken embryo with anti-polysialylated neural cell adhesion molecule (PSA-NCAM) and the HNK1 antibody against a sulfated carbohydrate epitope. The function of the His-Purkinje system was assayed using extracellular electrodes and high-resolution voltage-sensitive two-dimensional optical mapping. The appearance of the mature form of the His-Purkinje system delineated by the markers coincided with the onset of the mature electrophysiological pattern of ventricular activation. These data suggest that, at the completion of ventricular septation, the His-Purkinje system undergoes critical structural and functional transitions that impact on the global pattern of conduction and contraction of the developing four-chambered heart.

Action Potentials↗
PubMed2003

Patterning of the mouse conduction system.

The cardiac conduction system (CCS) is a network of cells responsible for the rhythmic and coordinated excitation of the heart. Components of the murine conduction system, including the peripheral Purkinje fibres, are morphologically indistinguishable from surrounding cardiomyocytes and there exists a paucity of molecular markers to specifically identify these cells. Recently, we identified a line of transgenic mice in which the lacZ reporter gene is expressed within the embryonic CCS beginning at 8.25 days post-conception (dpc); its expression appears to delineate the full extent of the CCS, including the distal Purkinje fibre network, throughout all subsequent stages of development. Moreover, using the highly sensitive technique of optical mapping of electrical activity in embryonic murine hearts, we provided evidence for functional specialization of components of the CCS as early as 10.5 dpc. Here, we summarize these findings and describe our initial efforts utilizing the CCS-lacZ mice to identify novel factors that promote CCS specialization.

Animals↗
PubMed1989

Normal numbers of retinotectal synapses during the activity-sensitive period of optic regeneration in goldfish: HRP-EM evidence implicating synapse rearrangement and collateral elimination during map refinement.

Optic and nonoptic fibers and synapses were counted in the primary optic innervation layer (S-SO-SFGS) in anteromedial tectum in normal goldfish and in fish 30, 60, and 240 d after the optic nerve was crushed. A newly developed "cold-fill" HRP-labeling protocol was used to label optic afferents for electron microscopy, and counts were then made on EM photomontages of columns through the HRP-labeled S-SO-SFGS. Normal numbers of retinotectal synapses were present at 30 d regeneration, at a time when activity-dependent refinement of the optic projection is incomplete. Normal numbers were also found at 60 and 240 d, when refinement is largely completed. In contrast to this constancy in optic synapse numbers, there was nearly 10 times the normal number of optic fibers in the SFGS at 30 d, and these were reduced by 50% at 60 d, remaining over 4 times normal at 240 d. These findings imply extensive rearrangement of optic synapses during map refinement. They also indicate that synapse rearrangement is associated with the elimination of optic collaterals.

Animals↗
PubMed2003

A first locus for isolated autosomal recessive optic atrophy (ROA1) maps to chromosome 8q.

In contrast to the frequent dominant optic atrophies (DOAs) in which the neuropathy is usually an isolated event, isolated recessive optic atrophies (ROAs) are very uncommon and have been described as severe congenital or early infantile conditions. To date, two loci for isolated DOA have been mapped, of which one was ascribed to mutations in the OPA1 gene. Conversely, no isolated autosomal ROA locus had previously been localised. Here, we report a large multiplex consanguineous family of French origin affected with an early onset but slowly progressive form of isolated OA. A genome-wide search for homozygosity allowed the localisation of the disease-causing gene to chromosome 8q21-q22 (Zmax of 3.41 at theta=0 for D8S270), in a 12 Mb interval flanked by markers D8S1702 and D8S1794. This localisation excludes allelism of the disease with both isolated DOAs, on one hand, or all known syndromic forms of ROA, on the other hand, supporting the mapping of a first gene for isolated autosomal ROA (ROA1) on the long arm of chromosome 8.

Child↗
PubMed2005

Mode mapping in paraxial lossless optics.

A Collins transformation maps an orthonormal set of Hermite-Gaussian modes into an orthonormal set of beams with a Gaussian envelope. Among these beams are Laguerre-Gaussian beams and the recently introduced Hermite-Laguerre-Gaussian beams. Compact expressions for the complex field amplitudes of these modes are derived. The results obtained are useful for description of the propagation of light through first-order optical systems, for the solution of the phase-retrieval problem by noninterferometric techniques, and for the design of mode converters and information processing systems.

Journal Article↗
PubMed1996

Optical and FDG mapping of frequency-specific activity in auditory cortex.

With optical recording of intrinsic signals (ORIS) and tone stimulation, we analysed frequency- and intensity-dependent spatio-temporal activity in primary auditory cortex AE of awake Mongolian gerbils. We found a two-dimensional and assymetric propagation of ORIS activity (1) from ventral to dorsal along isofrequency contours at all frequencies and (2) from the low-frequency end across the complete tonotopic gradient at low frequencies. High-frequency representations remained tonotopic. Tonotopic asymmetries were independent of stimulus intensity. By contrast, in fluoro-2-deoxyglucose images from the same animals metabolic activity was tonotopically confined at high and low frequencies. The assymetric tonotopic propagation of ORIS activity suggests subthreshold directional interaction mechanisms in the cortical network which may serve to relate low- to high-frequency components of complex sounds.

Acoustic Stimulation↗
PubMed2005

Repeatability and reproducibility of fast macular thickness mapping with stratus optical coherence tomography.

OBJECTIVE: To determine the repeatability and reproducibility of retinal thickness measurements with the fast macular thickness mapping protocol of Stratus optical coherence tomography. METHODS: Ten eyes of 10 healthy subjects and 15 eyes of 15 diabetic patients with clinically significant macular edema (CSME) underwent 2 scanning sessions before and after pupil dilation during the same visit by 2 experienced examiners. Healthy subjects also received a third scanning session during a second visit. Repeatability and reproducibility for the foveolar center and for each of 9 Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions were calculated by their repeatability and reproducibility coefficients and intraclass correlation coefficients. RESULTS: The coefficients of repeatability were less than 8% in healthy subjects and less than 9% in patients with diabetes and CSME. The reproducibility coefficients were less than 10% and 11% in healthy subjects and diabetic patients with CSME, respectively. There was no significant difference between scans acquired by different observers or during different visits. The intraclass correlation coefficients were always greater than 0.80 and 0.98 in healthy subjects and diabetic patients with CSME, respectively. Average +/- SD thickness was found to be 223 +/- 14 and 404 +/- 108 mum for the central ETDRS-like region in healthy subjects and diabetic patients with CSME, respectively. CONCLUSION: With the fast macular thickness mapping protocol of Stratus ocular coherence tomography, our results indicate that retinal thickness measurements in dilated and undilated eyes of healthy subjects and diabetic patients with CSME are repeatable and reproducible.

Adolescent↗
PubMed1981

A demonstration of several independent, partially overlapping, retinotopic maps in the optic tract of the cat.

We show here that the retina in the cat's optic tract by several separate, retino-topically organized maps. Fibers in different diameter classes form independent maps, and both hemi-retinae of the opposite side, as well as the temporal retina of the same side, are mapped in the tract. These several maps form rough topographic representations significantly out of register with each other.

Animals↗
PubMed2001

Voltage-sensitive dye versus intrinsic signal optical imaging: comparison of optically determined functional maps from rat barrel cortex.

Using intrinsic and voltage-sensitive dye optical imaging methods, somatosensory-evoked neural activity and the consequent metabolic activity were visualized in the barrel cortex at high temporal and spatial resolution. We compared maps of neural and metabolic activity from the perspective of spatial distribution in the cortex. There was good agreement between the two functional maps, if the extent of metabolic activity before a prominent increase in cerebral blood volume (CBV) was assessed. This result indicates that oxygen consumption occurs before CBV changes, in approximately the same cortical area as that in which the preceding neural activity was evoked. This also suggests that the intrinsic signal reflects subthreshold synaptic activity, as well as spiking activity, which is similar to the dye-related signals.

Afferent Pathways↗
PubMed1994

Adaptive plasticity of the auditory space map in the optic tectum of adult and baby barn owls in response to external ear modification.

1. This study demonstrates the influence of experience on the establishment and maintenance of the auditory map of space in the optic tectum of the barn owl. Auditory experience was altered either by preventing the structures of the external ears (the facial ruff and preaural flaps) from appearing in baby barn owls (baby ruff-cut owls) or by removing these structures in adults (adult ruff-cut owls). These structures shape the binaural cues used for localizing sounds in both the horizontal and vertical dimensions. 2. The acoustic effects of removing the external ear structures were measured using probe tube microphones placed in the ear canals. In both baby and adult ruff-cut owls, the spatial pattern of binaural localization cues was dramatically different from normal: interaural level difference (ILD) changed with azimuth instead of with elevation, the rate of change of ILD across space was decreased relative to normal, and the rate of change of interaural time difference (ITD) across frontal space was increased relative to normal. 3. The neurophysiological representations of ITD and ILD in the optic tectum were measured before and > or = 3 mo after ruff removal in adults and beginning at 4.5 months of age in baby ruff-cut owls. Multiunit tuning to ITD and to ILD was measured using dichotic stimulation in ketamine-anesthetized owls. The tectal maps of ITD and ILD were reconstructed using visual receptive field location as a marker for recording site location in the optic tectum. 4. Adjustment of the tectal map of ITD to the altered spatial pattern of acoustic ITD was essentially complete in adults as well as in baby ruff-cut owls. This adjustment changed the magnification of ITD across the tectum, with resultant changes in ITD tuning at individual tectal sites of up to approximately 25 microseconds (approximately 5% of the physiological range) relative to normal values. 5. Adaptation of the tectal ILD map to the ruff-cut spatial pattern of acoustic ILD was substantial but clearly incomplete in both adult and baby ruff-cut owls. Although changes of up to approximately 15 dB (approximately 47% of the physiological range) relative to normal tuning were observed at certain tectal sites, the topography of the ILD map was always intermediate between normal and that predicted by the ruff-cut spatial pattern of acoustic ILD.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗