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PubMed2004

Optical imaging of the heart.

Optical techniques have revolutionized the investigation of cardiac cellular physiology and advanced our understanding of basic mechanisms of electrical activity, calcium homeostasis, and metabolism. Although optical methods are widely accepted and have been at the forefront of scientific discoveries, they have been primarily applied at cellular and subcellular levels and considerably less to whole heart organ physiology. Numerous technical difficulties had to be overcome to dynamically map physiological processes in intact hearts by optical methods. Problems of contraction artifacts, cellular heterogeneities, spatial and temporal resolution, limitations of surface images, depth-of-field, and need for large fields of view (ranging from 2x2 mm2 to 3x3 cm2) have all led to the development of new devices and optical probes to monitor physiological parameters in intact hearts. This review aims to provide a critical overview of current approaches, their contributions to the field of cardiac electrophysiology, and future directions of various optical imaging modalities as applied to cardiac physiology at organ and tissue levels.

Action Potentials↗

PubMed1995

Optical mapping reveals that repolarization spreads anisotropically and is guided by fiber orientation in guinea pig hearts.

Guinea pig hearts were stained with a voltage-sensitive dye and imaged on a photodiode array to record fluorescent action potentials (APs) from 124 sites. Activation and repolarization patterns were recorded from the epicardium during stimulation at different loci and correlated with the underlying fiber architecture. Endocardial APs were recorded by inserting a light guide into the ventricular cavity or by dissecting out the ventricular free wall to expose the endocardium. In hearts paced on the right atrium to simulate sinus rhythm, activation emerged synchronously over a large area of the ventricular epicardium and spread laterally in 5 to 7 ms. The apparent longitudinal and transverse velocities were 2.66 +/- 0.11 and 1.65 +/- 0.09 m/s (n = 12). In contrast, repolarization began near the apex on the endocardium and spread transmurally in 6 +/- 1.3 ms (n = 12) and then anisotropically along the epicardium in 25 to 30 ms with apparent maximum (0.53 +/- 0.11 m/s) and minimum (0.31 +/- 0.10 m/s) repolarization velocities that aligned with the longitudinal and transverse axes of epicardial fibers. When paced on the epicardium, activation of intact hearts (n = 12) and perfused sheets (n = 8) was anisotropic, with longitudinal (0.85 +/- 0.05 m/s) and transverse (0.44 +/- 0.04 m/s) conduction velocities that aligned with the epicardial fiber orientation. When activation was initiated at different sites on the epicardium, repolarization always began near the apex and exhibited patterns similar to those obtained under right atrial pacing, but with slower longitudinal (0.41 +/- 0.09 m/s) and transverse (0.23 +/- 0.07 m/s) repolarization velocities (n = 18). In sheets stretched parallel to the longitudinal axis of surface fibers, AP durations (APDs) increased as a function of fiber length, from the length at zero developed tension to 120% of the length at maximum developed tension (Lmax). Spatial distributions of APDs did not change during stretches along the rising phase of the length-tension curve. In sheets stretched to 50% of Lmax, APDs were shorter and more homogeneous on the endocardium (mean APD, 188 ms; delta APD, 195-186 = 9 ms) than on the epicardium (mean APD, 204 ms; delta APD, 212-186 = 26 ms; n = 8). In guinea pig hearts, activation is rapid; therefore, repolarization depends primarily on intrinsic spatial heterogeneities of APDs. Consequently, repolarization begins at endocardial cells with the shortest APDs and spreads transmurally and then anisotropically on the surface according to the epicardial cell orientation.

Animals↗

PubMed2000

Interdependence of modulated dispersion and tissue structure in the mechanism of unidirectional block.

We previously showed that a premature stimulus can significantly alter vulnerability to arrhythmias by modulating spatial gradients of ventricular repolarization (ie, modulated dispersion). However, it is not clear if such changes in arrhythmia vulnerability can be attributed to the formation of an electrophysiological substrate for unidirectional block and what the potential role is of tissue structure in this process. Therefore, the main objective of the present study was to examine the concomitant effect repolarization gradients and tissue structure have on unidirectional block. Optical action potentials were recorded from 128 ventricular sites (1 cm(2)) in 8 Langendorff-perfused guinea pig hearts. Propagation was confined to the epicardial surface using an endocardial cryoablation procedure, and a 12-mm barrier with a 1.5-mm isthmus was etched with a laser onto the epicardium. A premature stimulus (S2) was delivered over a range of S1S2 coupling intervals to modulate repolarization gradients in a predictable fashion. When a second premature stimulus (S3) was delivered from the center of the isthmus, the occurrence and orientation of unidirectional block were highly dependent on repolarization gradients created by the S2 beat. In this model, a local repolarization gradient of 3.2 ms/mm was required for unidirectional block at this isthmus. In addition, the formation of unidirectional block was critically dependent on the presence of the source-sink mismatch imposed by the isthmus. These results may explain how the interplay between spatial heterogeneities of repolarization and tissue structure form a substrate for unidirectional block and reentry.

Action Potentials↗

PubMedDate not supplied

An interventional magnetic resonance imaging technique for the molecular characterization of intraprostatic dynamic contrast enhancement.

The biological characterization of an individual patient's tumor by noninvasive imaging will have an important role in cancer care and clinical research if the molecular processes that underlie the image data are known. Spatial heterogeneity in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI) is hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in a patients with prostate cancer.

Biopsy↗

PubMed1998

Abnormalities of gastric mucosal oxygenation in septic shock: partial responsiveness to dopexamine.

Splanchnic mucosal perfusion abnormalities have been implicated in the development of sepsis and multiorgan failure. We employed reflectance spectrophotometry for direct assessment of the microvascular hemoglobin oxygen saturation (HbiO2) and hemoglobin concentration (rel Hb(conc)) in the mucosa of the upper gastrointestinal tract. Owing to the high recording frequency together with a small catchment volume, assessment of spatial heterogeneity is enabled. Results were as follows: In healthy controls (n = 7), mean HbiO2 was 70.3 +/- 2.1%, with narrow dispersion and near-Gaussian distribution of the histogram. In patients presenting with hyperdynamic septic shock (n = 15) mean HbiO2 was reduced to 51.0 +/- 1.6% in spite of high normal whole-body oxygen delivery, with tailing of the histogram to severely hypoxic values (18.4 % of data < 40%). In parallel, markedly reduced rel Hb(conc) values were recorded and the standardized intramucosal pH (pHi) was lowered to 7.25 +/- 0.01. Short-term infusion of dopexamine (2 microg/kg/min) caused a significant rise in HbiO2 and rel Hb(conc), whereas whole-body oxygen uptake and standardized pHi values were not altered. In conclusion, decreased oxygenation and tissue hemoglobin concentration, with the appearance of severely hypoxic microdomains, were noted in patients with hyperdynamic sepsis, strongly suggesting pronounced microcirculatory disturbances in this compartment. The partial responsiveness of these abnormalities to dopexamine warrants further elucidation.

Adult↗

PubMed1999

Regional expansion of oleic acid-injured lungs.

It has been suggested that dependent regions of an injured lung are collapsed and subject to cyclic reopening and collapse during mechanical ventilation. To test this hypothesis, we measured both temporal and spatial heterogeneity of lobar expansion in oleic acid (OA)-injured dogs. Regional volumes were measured in nine dogs (seven supine and two prone) during closed loop sinusoidal oscillations of the lungs before and after OA injury using the parenchymal marker technique. In contrast to computer tomography, the parenchymal marker technique provides absolute measures of regional tissue dimensions as opposed to relative measures of regional air to liquid content. The experiments generated three major findings: (1) OA injury did not lead to the collapse of dependent lung units at FRC, (2) OA injury did not steepen the vertical gradient in regional lung volumes at FRC, and (3) during sinusoidal oscillation of the OA-injured lungs from FRC, dependent regions did not undergo cyclic reopening and collapse. On the basis of these results, we propose an alternative mechanism for the topographic variability in regional impedances and lung expansion after injury, namely liquid and foam in conducting airways.

Animals↗

PubMed2005

ABCA4-associated retinal degenerations spare structure and function of the human parapapillary retina.

PURPOSE: To study the parapapillary retinal region in patients with ABCA4-associated retinal degenerations. METHODS: Patients with Stargardt disease or cone-rod dystrophy and disease-causing variants in the ABCA4 gene were included. Fixation location was determined under fundus visualization, and central cone-mediated vision was measured. Intensity and texture abnormalities of autofluorescence (AF) images were quantified. Parapapillary retina of an eye donor with ungenotyped Stargardt disease was examined microscopically. RESULTS: AF images ranged from normal, to spatially homogenous abnormal increase of intensity, to a spatially heterogenous speckled pattern, to variably sized patches of low intensity. A parapapillary ring of normal-appearing AF was visible at all disease stages. Quantitative analysis of the intensity and texture properties of AF images showed the preserved region to be an annulus, at least 0.6 mm wide, surrounding the optic nerve head. A similar region of relatively preserved photoreceptor nuclei was apparent in the donor retina. In patients with foveal fixation, there was better cone sensitivity at a parapapillary locus in the nasal retina than at the same eccentricity in the temporal retina. In patients with eccentric fixation, approximately 30% had a preferred retinal locus in the parapapillary retina. CONCLUSIONS: Human retinal degenerations caused by ABCA4 mutations spare the structure of retina and RPE in a circular parapapillary region that commonly serves as the preferred fixation locus when central vision is lost. The retina between fovea and optic nerve head could serve as a convenient, accessible, and informative region for structural and functional studies to determine natural history or outcome of therapy in ABCA4-associated disease.

ATP-Binding Cassette Transporters↗

PubMed1998

Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma.

A massive infiltration of the skin by activated CD8+ T lymphocytes involving both the dermis and the epidermis has been found in HIV-1-infected patients presenting with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ junctional diversity of the skin-infiltrating lymphocytes (SILs) in four patients. The SILs expressed a limited set of TCRBV gene segments. Complementarity determining region 3 length analysis further emphasized their oligoclonality, suggesting that antigen stimulation might be responsible for the cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from the same individual were shown to harbor distinct T cell repertoires, possibly reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol-expressing target cells, whereas CTL lines derived from the skin lesions of a second patient were shown to be predominantly Env-specific. Taken together, these data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV-infected patients, and suggest that in addition to their known role in controlling the retroviral infection, these CTLs may also be involved in the pathogenesis of cutaneous inflammatory disorders occurring during the course of HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Patterns of malaria-related hospital admissions and mortality among Malawian children: an example of spatial modelling of hospital register data.

BACKGROUND: Malaria is a leading cause of hospitalization and in-hospital mortality among children in Africa, yet, few studies have described the spatial distribution of the two outcomes. Here spatial regression models were applied, aimed at quantifying spatial variation and risk factors associated with malaria hospitalization and in-hospital mortality. METHODS: Paediatric ward register data from Zomba district, Malawi, between 2002 and 2003 were used, as a case study. Two spatial models were developed. The first was a Poisson model applied to analyse hospitalization and minimum mortality rates, with age and sex as covariates. The second was a logistic model applied to individual level data to analyse case-fatality rate, adjusting for individual covariates. RESULTS AND CONCLUSION: Rates of malaria hospitalization and in-hospital mortality decreased with age. Case fatality rate was associated with distance, age, wet season and increased if the patient was referred to the hospital. Furthermore, death rate was high on first day, followed by relatively low rate as length of hospital stay increased. Both outcomes showed substantial spatial heterogeneity, which may be attributed to the varying determinants of malaria risk, health services availability and accessibility, and health seeking behaviour. The increased risk of mortality of children referred from primary health facilities may imply inadequate care being available at the referring facility, or the referring facility are referring the more severe cases which are expected to have a higher case fatality rate. Improved prognosis as the length of hospital stay increased suggest that appropriate care when available can save lives. Reducing malaria burden may require integrated strategies encompassing availability of adequate care at primary facilities, introducing home or community case management as well as encouraging early referral, and reinforcing interventions to interrupt malaria transmission.

Adolescent↗

PubMed2004

Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence.

BACKGROUND: In the global program for the elimination of lymphatic filariasis (LF) longitudinal assessment of the prevalence of microfilaremia and antigenemia is recommended to monitor the effect of mass treatment on transmission. Additional monitoring tools such as entomologic and antibody methods may be useful in identifying residual foci of infection. In this study, we characterized serologic markers of infection and exposure spatially both before and after mass treatment, in an area of initial low Wuchereria bancrofti infection prevalence. METHODS: Consenting persons in the sentinel community were tested for circulating microfilaria and antigen (by immunochromatographic test) before and after the 1st annual mass drug administration of diethylcarbamazine and albendazole. A cohort of 161 persons provided serum specimens both years that were tested for antifilarial IgG (1 and 4) antibody. Every house was mapped using a differential Global Positioning System; this information was linked to the serologic data. W. bancrofti infection in the mosquito vector was assessed with year-round collection. Multiple linear regression was used to investigate the influence of antigen-positive persons on the antifilarial antibody responses of antigen-negative neighbors. RESULTS: After mass treatment, decreases were observed in the sentinel site in the overall prevalence of antigen (10.4% to 6.3%) and microfilaremia (0.9 to 0.4%). Of the persons in the cohort that provided serum specimens both years, 79% received treatment. Antigen prevalence decreased from 15.0% to 8.7%. Among 126 persons who received treatment, antigen and antifilarial IgG1 prevalence decreased significantly (p = 0.002 and 0.001, respectively). Among 34 persons who did not receive treatment, antifilarial IgG1 prevalence increased significantly (p = 0.003). Average antifilarial IgG1 levels decreased in households with high treatment coverage and increased in households that refused treatment. Each 10-meter increase in distance from the residence of a person who was antigen-positive in 2000 was associated a 4.68 unit decrease in antifilarial IgG1 level in 2001, controlling for other factors (p = 0.04). DISCUSSION: Antifilarial antibody assays can be used as a measure of filarial exposure. Our results suggest that micro-scale spatial heterogeneity exists in LF exposure and infection. Treatment appeared to be associated with reduced exposure at the sub-community level, suggesting the need to achieve high and homogeneous coverage. Public health messages should note the benefits of having one's neighbors receive treatment with antifilarial drugs.

Journal Article↗

PubMed1992

The effects of extracellular calcium and epinephrine on cytosolic-free calcium in single rat adipocytes.

Changes in cytosolic calcium concentration ([Ca2+]i) in response to extracellular calcium and epinephrine were monitored in individual rat adipocytes by both photon counting and digital imaging techniques utilizing the intracellular fluorescent calcium probes Fura-2 and Indo-1. Adipocytes containing Fura-2 were attached to coverslips and shown to be as hormonally responsive to insulin as adipocytes in suspension [3.5 +/- 0.8 (n = 5) vs. 4.2 +/- 0.6 (n = 8)-fold increase in glucose oxidation over basal in response to 0.7 nM insulin]. Basal [Ca2+]i in single rat adipocytes was found to be 128 +/- 6 nM (n = 100). The addition of either extracellular calcium or epinephrine elicited transient, concentration-dependent increases in [Ca2+]i. Although the characteristics of calcium- and epinephrine-induced calcium transients are generally similar, the peak [Ca2+]i increase over basal is higher in response to calcium vs. epinephrine [37 and 64% (1 and 27 microM epinephrine), vs. 132 and 236% (2 and 4 mM calcium)]. All the cells tested responded to calcium but only 67% responded to epinephrine. Both alpha- and beta-adrenergic agonists were able to increase [Ca2+]i. The epinephrine-induced [Ca2+]i transients appear to be dependent upon extra-cellular calcium. Neither cholera nor pertussis toxin treatments altered basal [Ca2+]i. However, after treatment of adipocytes with either pertussis or cholera toxin, epinephrine stimulated oscillations in [Ca2+]i. Digital imaging revealed that adipocytes demonstrate a high degree of intracellular spatial heterogeneity and intercellular variability in the magnitude of response to both calcium and epinephrine. These studies demonstrate the feasibility of using single rat adipocytes to monitor intracellular free calcium, using both photon counting and digital imaging.

Adipose Tissue↗

PubMed1998

Dynamic changes in prolactin promoter activation in individual living lactotrophic cells.

The firefly luciferase gene has become widely used as a convenient reporter for studies of gene promoter regulation. Very recently, the development of ultralow-light imaging cameras has enabled the quantitative digital imaging of light signals resulting from luciferase activation in the presence of luciferin substrate. We have applied this technology to the study of PRL promoter activation in individual pituitary tumor cells to study the temporal and spatial characteristics of the expression of a well-characterized pituitary hormone gene. Rat pituitary GH3 cells were transfected by lipofection with a luciferase reporter gene linked to 5000 bp from the human PRL gene 5'-flanking region. A series of stably transfected cell clones were generated, and one of these was chosen for detailed study on the basis of appropriate regulation of high-level luciferase expression by a series of known stimuli including TRH, forskolin, the calcium channel agonist Bay K8644, and basic fibroblast growth factor (bFGF). These cells were subjected to direct imaging of luciferase activity using a Hamamatsu photon-counting camera linked to a Zeiss Axiovert microscope with an Argus-50 image processor. Cells were exposed to 1 mM luciferin, and images were integrated over 30-min periods for up to 72 h. The total photon count over a given field settled to steady levels within 10 h and then remained constant for over 55 h. Addition of forskolin, TRH, or bFGF increased the total photon count of fields of 20-100 cells by 2- to 4-fold consistent with previous data from transient expression assays using the human PRL promoter. Individual cells, on the other hand, showed marked marked temporal and spatial heterogeneity and variability of luciferase expression when studied at 3-h intervals. Unstimulated cells showed variable luciferase expression with up to 40-fold excursions in photon counts per single cell area within 12-h periods. Stimulation of cells with either TRH, forskolin, or bFGF resulted in smooth increases in photon output over fields of 20-100 cells, but again individual cell responses differed widely, with some cells showing slow progressive rises in photon output, others showing phasic or transient responses, and yet others showing no response. In conclusion, we found a surprising degree of heterogeneity and temporal variability in the level of gene expression in individual living pituitary tumor cells over long periods of time, with markedly divergent responses to hormonal or intracellular stimulation. The use of stably transfected clonal cell lines with extended periods of reporter gene imaging offers a valuable insight into control of gene expression in living cells in real time.

Animals↗

PubMed2004

Simulation of calcium waves in ascidian eggs: insights into the origin of the pacemaker sites and the possible nature of the sperm factor.

Fertilization triggers repetitive waves of cytosolic Ca(2+) in the egg of many species. The mechanism involved in the generation of Ca(2+) waves has been studied in much detail in mature ascidian eggs, by raising artificially the level of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] or of its poorly metabolizable analogue, glycero-myo-phosphatidylinositol 4,5-bisphosphate [gPtdIns(4,5)P(2)]. Here, we use this strategy and the experimental results it provides to develop a realistic theoretical model for repetitive Ca(2+) wave generation and propagation in mature eggs. The model takes into account the heterogeneous spatial distribution of the endoplasmic reticulum. Our results corroborate the hypothesis that Ca(2+) wave pacemakers are associated with cortical accumulations of endoplasmic reticulum. The model is first tested and validated by the adequate match between its theoretical predictions and the observed effects of localized injections of massive amounts of Ins(1,4,5)P(3) analogues. In a second step, we use the model to make some propositions about the possible characteristics of the sperm factor. We find that to account for the spatial characteristics of the first series of Ca(2+) waves seen at fertilization in ascidian eggs, it has to be assumed that, if the sperm factor is a phospholipase C, it is Ca(2+)-sensitive and highly diffusible. Although the actual state of knowledge does not allow us to explain the observed relocalization of the Ca(2+) wave pacemaker site, the model corroborates the assumption that PtdIns(4,5)P(2), the substrate for phospholipase C is distributed over the entire egg. We also predict that the dose of sperm factor injected into the egg should modulate the temporal characteristics of the first, long-lasting fertilization wave.

Animals↗

PubMed2002

Transient pluripotent cell populations during primitive ectoderm formation: correlation of in vivo and in vitro pluripotent cell development.

Formation and differentiation of a pluripotent cell population is central to mammalian development, and the isolation, identification and manipulation of human pluripotent cells is predicted to be of therapeutic use. Within the early mammalian embryo, two distinct populations of pluripotent cells have been described: the inner cell mass (ICM), which differentiates to form a second pluripotent cell populations, the primitive ectoderm. Indirect evidence suggests the existence of temporally distinct intermediate pluripotent cell populations as primitive ectoderm is formed. We coupled an in vitro model of primitive ectoderm formation (the transition of embryonic stem cells to early primitive ectoderm-like (EPL) cells) with ddPCR-based techniques to identify three novel genes, Psc1, CRTR-1 and PRCE, that were expressed differently during pluripotent cell progression. Detailed mapping of these genes with Oct4, Rex1 and Fgf5 on pregastrulation embryos provided the first molecular evidence for the existence of successive, temporally distinct pluripotent cell populations in the embryo between the ICM and primitive ectoderm. No evidence was found for spatial heterogeneity within the Oct4(+) pool. The transition between populations correlated with morphological or developmental alterations in pluripotent cells in vivo. Genes that are temporally expressed during pluripotent cell progression may provide an opportunity for molecular discrimination of pluripotent cells at different stages of maturation in vivo and an understanding of the cellular origins and properties of pluripotent cell lines isolated from diverse sources. Furthermore, the strong correlation of gene expression demonstrated between EPL cell formation in vitro and primitive ectoderm formation in vivo validates EPL cells as a model for primitive ectoderm, thereby providing a model system for the investigation of pluripotent differentiation and an opportunity for directed differentiation of pluripotent cells to therapeutically useful cell populations.

Amino Acid Sequence↗

PubMed2004

Spatial organization of visuomotor reflexes in Drosophila.

In most animals, the visual system plays a central role in locomotor guidance. Here, we examined the functional organization of visuomotor reflexes in the fruit fly, Drosophila, using an electronic flight simulator. Flies exhibit powerful avoidance responses to visual expansion centered laterally. The amplitude of these expansion responses is three times larger than those generated by image rotation. Avoidance of a laterally positioned focus of expansion emerges from an inversion of the optomotor response when motion is restricted to the rear visual hemisphere. Furthermore, motion restricted to rear quarter-fields elicits turning responses that are independent of the direction of image motion about the animal's yaw axis. The spatial heterogeneity of visuomotor responses explains a seemingly peculiar behavior in which flies robustly fixate the contracting pole of a translating flow field.

Animals↗

PubMed2006

Air-flow sensitive hairs: boundary layers in oscillatory flows around arthropod appendages.

The aim of this work is to characterize the boundary layer over small appendages in insects in longitudinal and transverse oscillatory flows. The problem of immediate interest is the early warning system in crickets perceiving flying predators using air-flow-sensitive hairs on cerci, two long appendages at their rear. We studied both types of oscillatory flows around small cylinders using stroboscopic micro-particle image velocimetry as a function of flow velocity and frequency. Theoretical predictions are well fulfilled for both longitudinal and transverse flows. Transverse flow leads to higher velocities than longitudinal flow in the boundary layer over a large range of angles between flow and cylinder. The strong spatial heterogeneity of flow velocities around filiform-shaped appendages is a rich source of information for different flow-sensing animals. Our results suggest that crickets could perceive the direction of incoming danger by having air-flow-sensitive hairs positioned around their entire cerci. Implications for biomimetic flow-sensing MEMS are also presented.

Air Movements↗

PubMed2002

The relationship between heat flow and vasculature in the dorsal fin of wild bottlenose dolphins Tursiops truncatus.

The dorsal fin of the bottlenose dolphin Tursiops truncatus contains blood vessels that function either to conserve or to dissipate body heat. Prior studies have demonstrated that heat flux, measured from a single position on the dorsal fin, decreases during body cooling and diving bradycardia and increases after exercise and at the termination of the dive response. While prior studies attributed changes in heat flux to changes in the pattern of blood flow, none directly investigated the influence of vascular structures on heat flux across the dorsal fin. In this study we examined whether heat flux is higher directly over a superficial vein, compared to a position away from a vein, and investigated the temporal relationship between heart rate, respiration and heat flux. Simultaneous records of heat flux and skin temperature at three positions on the dorsal fins of 19 wild bottlenose dolphins (with the fin in air and submerged) were collected, together with heart rate and respiration. When the fin was submerged, heat flux values were highest over superficial veins, usually at the distal tip, suggesting convective delivery of heat, via blood, to the skin's surface. Conversely, in air there was no relationship between heat flux and superficial vasculature. The mean difference in heat flux (48 W m(-2)) measured between the three fin positions was often equal to or greater than the heat flux that had been recorded from a single position after exercising and diving in prior studies. Tachycardia at a respiratory event was not temporally related to an increase in heat flux across the dorsal fin. This study suggests that the dorsal fin is a spatially heterogeneous thermal surface and that patterns of heat flux are strongly influenced by underlying vasculature.

Animals↗

PubMed2006

Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles.

BACKGROUND: Arsenic trioxide (As(2)O (3)) is a new promising regimen for patients with a relapse of acute promyelocytic leukemia (APL), but causes life-threatening arrhythmias. This study aimed to investigate the incidence and mechanism of arrythmogenesis caused by As(2)O(3). METHODS AND RESULTS: Standard 12-lead ECGs were monitored throughout As(2)O(3) therapy in 20 APL patients. As(2)O (3) (0.15 mg/kg) significantly prolonged the corrected QT interval (QTc: 445+/-7 to 517+/-17 ms, means+/-SE, p<0.01), and also increased the QTc dispersion and transmural dispersion of repolarization. Non-sustained ventricular tachycardias and torsades de pointes occurred in 4 and 1 patients, respectively. The action potentials and isometric contraction were measured in guinea pig papillary muscles during As(2)O (3) perfusion (350 micromol/L). The action potential duration was prolonged (APD(90): 150+/-11 to 195+/-12 ms at 60 min, p<0.01, n=5) and perfusion of As(2)O(3) in a low K(+) solution with a low stimulation rate augmented the prolongation of APD, and provoked early after-depolarizations and triggered activities. The prolonged exposure to As(2)O(3) induced muscle contracture, aftercontractions, triggered activities and electromechanical alternans. Tetrodotoxin or butylated hydroxytoluene partially prevented the As(2)O(3)-induced prolongation of APD. CONCLUSIONS: The prolonged QTc and spatial heterogeneity are responsible for the As(2)O(3)-induced ventricular tachyarrhythmias. In addition to prolongation of the APD, cellular Ca(2+) overload and lipid peroxidation might contribute to the electrophysiological abnormalities caused by As(2)O(3).

Action Potentials↗