Atrial fibrillation in immigrant groups::a cohort study of all adults 45 years of age and older in Sweden

To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs ≤ 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke

Bifurcation analysis of a periodically forced relaxation oscillator: Differential model versus phase-resetting map

We compare the dynamics of the periodically forced FitzHugh-Nagumo oscillator in its relaxation regime to that of a one-dimensional discrete map of the circle derived from the phase-resetting response of this oscillator _the “phase-resetting map”_. The forcing is a periodic train of Gaussian-shaped pulses, with the width of the pulses much shorter than the intrinsic period of the oscillator. Using numerical continuation techniques, we compute bifurcation diagrams for the periodic solutions of the full differential equations, with the stimulation period being the bifurcation parameter. The period-1 solutions, which belong either to isolated loops or to an everywhere-unstable branch in the bifurcation diagram at sufficiently small stimulation amplitudes, merge together to form a single branch at larger stimulation amplitudes. As a consequence of the fast-slow nature of the oscillator, this merging occurs at virtually the same stimulation amplitude for all the period-1 loops. Again using continuation, we show that this stimulation amplitude corresponds, in the circle map, to a change of topological degree from one to zero. We explain the origin of this coincidence, and also discuss the translational symmetry properties of the bifurcation diagram

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture

<div><p>Background</p><p>Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown.</p><p>Objective</p><p>To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes.</p><p>Methods</p><p>We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4–6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs).</p><p>Results</p><p>Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD₃₀). APD₅₀ and APD₈₀ were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (I_Ca-L) and ~30% reduction (p<0.05) in the transient outward potassium current (I_TO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001).</p><p>Conclusions</p><p>SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.</p></div

Cav1.2 Localization and whole cell protein content is not affected by stearic acid.

<p>Transmitted light image of an atrial myocyte (top), Cav1.2 protein staining (green), α-actinin staining (red) and a merged image of Cav1.2, α-actinin and DAPI staining (bottom) under control (CTL; Panel A) and following incubation in stearic acid (SA; Panel B). Inset: 20 μm section of the merged image and corresponding intensity profile of Cav1.2 and α-actinin. Scale bars 20 μm. Panel C: Quantification of the intensity profiles shows SA did not alter the mean distance between intensity peaks for Cav1.2 (left) or α-actinin (right; n = 12, 12). Panel D: (left) Western blot for Cav1.2, with GAPDH as a control. Pane D: (right) normalized densitometry plot of Cav1.2 protein levels in CTL and SA treated cell lysates (n = 3).</p

Electrophysiological properties of atrial myocytes incubated in palmitic (PA), stearic (SA), oleic (OA) acids and vehicle control (CTL).

<p>Acquisition of Resting Membrane Potential (RMP), Action Potential (AP) Amplitude, Action Potential Overshoot, dv/dt_max, and Cell Capacitance by patch clamp is presented with animal matched controls (CTL). (*p<0.05).</p><p>Electrophysiological properties of atrial myocytes incubated in palmitic (PA), stearic (SA), oleic (OA) acids and vehicle control (CTL).</p

Rapidly and slowly activating components of delayed rectifier K+ current in guinea-pig sino-atrial node pacemaker cells

The components and properties of the delayed rectifier K+ current (IK) in isolated guinea-pig sino-atrial (SA) node pacemaker cells were investigated using the whole-cell configuration of the patch-clamp technique. An envelope of tails test was conducted by applying depolarizing pulses from a holding potential of −50 mV to +30 mV for various durations ranging from 40 to 2000 ms. The ratio of the tail current amplitude elicited upon return to the holding potential to the magnitude of the time-dependent outward current activated during depolarizing steps was dependent on the pulse duration, while after exposure to the selective IKr inhibitor E-4031 (5 μm) this current ratio became practically constant irrespective of the pulse duration. These observations are consistent with the presence of the E-4031-sensitive, rapidly activating and E-4031-resistant, slowly activating components of IK (IKr and IKs, respectively) in guinea-pig SA node cells. The activation range for IKr, defined as the E-4031-sensitive current (half-maximal activation voltage (V1/2) of −26.2 mV) was much more negative than that for IKs, defined as the E-4031-resistant current (V1/2 of +17.2 mV). IKr exhibited a marked inward rectification at potentials positive to −50 mV, whereas IKs showed only a slight rectification. In the current-clamp experiments, bath application of E-4031 (0.5 and 5 μm) initially slowed the repolarization at potentials negative to approximately −30 mV and produced a significant depolarization of the maximum diastolic potential, followed by the arrest of electrical activity, thus indicating that the late phase of the repolarization leading to the maximum diastolic potential at around −60 mV in spontaneous action potentials is primarily produced by IKr in guinea-pig SA node cells. External application of the selective IKs inhibitor 293B (30 μm) also delayed the repolarization process at potentials negative to about −20 mV and induced moderate depolarization of the maximum diastolic potential leading to the arrest of the spontaneous activity. These results provide evidence to suggest that both IKr and IKs are present and play crucial roles in the spontaneous electrical activity of guinea-pig SA node pacemaker cells

Stearic Acid disrupts t-tubules in atrial myocytes.

<p>Panel A (top): Coordinate axes for reference and schematic diagrams illustrating the fields of view. Panel A: subpanels (a, c, e & g) are XY planar views and (b, d, f & h) are 40 μm ZY cross-sectional views of the same cell. (a & b) Di-8-ANEPPS staining of t-tubules in freshly dissociated (<i>t</i> = 0) atrial myocytes (n = 19). After 24 hrs in culture, Control (CTL) cells shown in (c) and (d) retain t-tubule structures (n = 20). (e) and (f) T-tubular structure after chronic incubation of myocytes in PA (n = 19). (g) and (h) reduction in t-tubules after 24 hr incubation of myocytes in SA (n = 25). Arrows indicate the lateral membrane and arrowheads highlight an individual t-tubule in both views. (*) identifies the nuclear region. Scale bars: 20 μm (XY) and 5 μm (ZY). Panel B: Quantification of t-tubules in using the ratio of the t-tubule region and total cell fluorescence. SA reduced the presence of t-tubule structures in LA myocytes (CTL vs. SA; ***p<0.0001, n = 25), CTL vs. PA; p = ns (n = 19)). Panel C: SA reduced the capacitance of atrial myocytes following incubation in SA (Panel C, n = 83 *p<0.05), but did not alter 2D surface area of myocytes (n = 68).</p