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Cardiac Purkinje fibers and arrhythmias; The GK Moe Award Lecture 2015.

ABSTRACT: Purkinje fibers/cells continue to be a focus of arrhythmologists. Here we review several new ideas that have emerged in the literature and fold them into important new points. These points include the following: some proteins in Purkinje cells are specific to Purkinjes; pacemaker function in Purkinje may be similar to that of the sinus node cell; sink-source concerns about tracts/sheets of Purkinje fibers; role of Ito in arrhythmias; and genetic lesions in Purkinjes and their high impact on cardiac rhythm. Although new ideas about the remodeled Purkinje cell are not the focus of this review, one can easily imagine how Purkinjes and their function may be altered in diseased hearts.

SUBMITTER: Boyden PA

PROVIDER: S-EPMC4879678 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Cardiac Purkinje fibers and arrhythmias; The GK Moe Award Lecture 2015.

Boyden Penelope A PA Dun Wen W Robinson Richard B RB

Heart rhythm 20160113 5

Purkinje fibers/cells continue to be a focus of arrhythmologists. Here we review several new ideas that have emerged in the literature and fold them into important new points. These points include the following: some proteins in Purkinje cells are specific to Purkinjes; pacemaker function in Purkinje may be similar to that of the sinus node cell; sink-source concerns about tracts/sheets of Purkinje fibers; role of Ito in arrhythmias; and genetic lesions in Purkinjes and their high impact on card ...[more]

PMID: 26775142

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Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: role of purkinje fibers and triggered activity.

Project description:RationaleRecurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome.ObjectiveWe tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (V(m)) to elevated intracellular calcium (Ca(i)) (high diastolic Ca(i)-voltage coupling gains).Methods and resultsWe simultaneously mapped Ca(i) and V(m) on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca(i) elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 micromol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 mumol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Ca(i)-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). I(K1) suppression with CsCl (5 mmol/L, n=3), BaCl(2) (3 micromol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca(i)-voltage coupling gain and enabled epicardium to also generate TAs.ConclusionsHigher diastolic Ca(i)-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. I(K)(1) is a major factor that determines the diastolic Ca(i)-voltage coupling gain.

| S-EPMC2818796 | biostudies-literature

Materials Best Paper Award 2015.

Project description:Materials has established an annual award for the best article and for the best review published in Materials in order to acknowledge the outstanding contributions of our authors in the area of materials science and engineering.[...].

| S-EPMC5455272 | biostudies-other

Spatiotemporally Non-Uniform Ca2+ Dynamics of Cardiac Purkinje Fibers in Mouse Myocardial Infarct.

Project description:Surviving Purkinje fibers in myocardial infarct are regarded as an important substrate in arrhythmogenesis. However, poorly understood are functional properties of Purkinje fibers in the infarcted heart. We sought to visualize intracellular Ca2+ ([Ca2+]i) dynamics of Purkinje fiber networks in the mouse myocardial infarct. Using 3- to 4-day-old or 7- to 9-day-old infarcted hearts after the left coronary-artery ligation corresponding, respectively, to acute or healing phase, we conducted rapid fluo4-fluorescence imaging on the endocardial surface of the left ventricular septum by macro-zoom fluorescence microscopy and rapid-scanning confocal microscopy. In contrast with the intact heart, where uniform Ca2+ transients propagated rapidly, the infarcted heart exhibited slow, non-uniform impulse propagations. On confocal microscopy, Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics: beat-to-beat alternans of the Ca2+ transient amplitude in and among the individual fibers, whereas the intact fibers exhibited uniform Ca2+ transients. Such non-uniform [Ca2+]i dynamics were more conspicuous in the acute infarcted hearts than in the healing ones. In accordance with [Ca2+]i dynamics, fixed fluo4-loaded heart preparations exhibited definitive connexin-40 plaques in the peri-infarct Purkinje fibers, whereas the subjacent myocardium presented coagulative necrosis and granulation tissues, respectively. The surviving Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics, which may lead to arrhythmogenesis.

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The 2016 John J. Abel Award Lecture: Targeting the Mechanical Microenvironment in Cancer.

Project description:Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiology research field. Then we specially focus on mechanotransduction pathways in cancer progression and describe in detail the key signaling components of such mechanotransduction pathways and extracellular matrix components that are altered in cancer. Although our understanding of mechanoregulation in cancer is still in its infancy, some agents against key mechanoregulators have been developed and will be discussed to explore the potential of pharmacologically targeting mechanotransduction in cancer.

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Regional anesthesia: advancing the practice of medicine; the 2008 Gaston Labat Award lecture.

Project description: Not available

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Leveraging Genetics to Improve Cardiovascular Health in Diabetes: The 2018 Edwin Bierman Award Lecture.

Project description:The past decade has witnessed an exponential increase in our ability to search the genome for genetic factors predisposing to cardiovascular disease (CVD) and in particular coronary heart disease (CHD). Identifying these genes could lead to the development of innovative strategies to prevent the cardiovascular complications of diabetes by allowing us to 1) create predictive algorithms for the identification of patients at especially high risk of CVD so that these individuals can undergo preventive interventions early in the natural history of the disease; 2) discover as yet unknown disease pathways linking diabetes to atherosclerosis, which can be used as targets for the development of new CVD-preventing drugs specifically directed at subjects with diabetes; and 3) devise personalized programs increasing the cost-effectiveness of preventive interventions by tailoring them to the genetic background of each patient. Substantial progress has been made in each of these three areas as exemplified by the recent development of a CHD genetic risk score improving CHD prediction among subjects with type 2 diabetes, the discovery of a diabetes-specific CHD locus on 1q25 pointing to glutamine synthase (GLUL) and the ?-glutamyl cycle as key regulators of CHD risk in diabetes, and the identification of two genetic loci allowing the selection of patients with type 2 diabetes who may especially benefit from intensive glycemic control. Translating these discoveries into clinical practice will not be without challenges, but the potential rewards, from the perspective of public health as well as that of persons with diabetes, make this goal worth pursuing.

| S-EPMC6385753 | biostudies-literature

The Glenn A. Fry Award Lecture 2012: Plasticity of the visual system following central vision loss.

Project description:Following the onset of central vision loss, most patients develop an eccentric retinal location outside the affected macular region, the preferred retinal locus (PRL), as their new reference for visual tasks. The first goal of this article is to present behavioral evidence showing the presence of experience-dependent plasticity in people with central vision loss. The evidence includes the presence of oculomotor re-referencing of fixational saccades to the PRL; the characteristics of the shape of the crowding zone (spatial region within which the presence of other objects affects the recognition of a target) at the PRL are more "foveal-like" instead of resembling those of the normal periphery; and the change in the shape of the crowding zone at a para-PRL location that includes a component referenced to the PRL. These findings suggest that there is a shift in the referencing locus of the oculomotor and the sensory visual system from the fovea to the PRL for people with central vision loss, implying that the visual system for these individuals is still plastic and can be modified through experiences. The second goal of the article is to demonstrate the feasibility of applying perceptual learning, which capitalizes on the presence of plasticity, as a tool to improve functional vision for people with central vision loss. Our finding that visual function could improve with perceptual learning presents an exciting possibility for the development of an alternative rehabilitative strategy for people with central vision loss.

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The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: drug metabolism to therapeutics for chronic pain.

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3D magnetization transfer (MT) for the visualization of cardiac free-running Purkinje fibers: an ex vivo proof of concept.

Project description:ObjectivesWe investigate the possibility to exploit high-field MRI to acquire 3D images of Purkinje network which plays a crucial role in cardiac function. Since Purkinje fibers (PF) have a distinct cellular structure and are surrounded by connective tissue, we investigated conventional contrast mechanisms along with the magnetization transfer (MT) imaging technique to improve image contrast between ventricular structures of differing macromolecular content.MethodsThree fixed porcine ventricular samples were used with free-running PFs on the endocardium. T1, T2*, T2, and M0 were evaluated on 2D slices for each sample at 9.4 T. MT parameters were optimized using hard pulses with different amplitudes, offset frequencies and durations. The cardiac structure was assessed through 2D and 3D T1w images with isotropic resolutions of 150 µm. Histology, immunofluorescence, and qPCR were performed to analyze collagen contents of cardiac tissue and PF.ResultsAn MT preparation module of 350 ms duration inserted into the sequence with a B1 = 10 µT and frequency offset = 3000 Hz showed the best contrast, approximately 0.4 between PFs and myocardium. Magnetization transfer ratio (MTR) appeared higher in the cardiac tissue (MTR = 44.7 ± 3.5%) than in the PFs (MTR = 25.2 ± 6.3%).DiscussionMT significantly improves contrast between PFs and ventricular myocardium and appears promising for imaging the 3D architecture of the Purkinje network.

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Cardiac metabolism and arrhythmias.

Project description: Not available

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