Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarisations and fibrillation

Aims: Atrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms. Methods and results: In Langendorff-perfused rabbit hearts, under beta-adrenergic-stimulation with isoproterenol (1 µM; ISO), 8 weeks MI decreased AF threshold, indicating increased AF-susceptibility. This was associated with increased atrial action potential duration-alternans at 90% repolarisation, by 147%, and no significant change in mean APD or atrial global conduction velocity (n=6-13 non-MI hearts, 5-12 MI). In atrial isolated myocytes, also under beta-stimulation, L-type Ca2+ current (ICaL) density and intracellular Ca2+-transient amplitude were decreased by MI, by 35% and 41%, respectively, and the frequency of spontaneous depolarisations (SDs) was substantially increased. MI increased atrial myocyte size and capacity, and markedly decreased transverse-tubule density. In non-MI hearts perfused with ISO, the ICaL-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent ICaL-reduction (35%) to that from the MI, did not affect AF-susceptibility, and decreased APD. Conclusion: chronic MI in rabbits remodels atrial structure, electrophysiology and intracellular Ca2+-handling. Increased susceptibility to AF by MI, under beta-adrenergic-stimulation, may result from associated production of atrial APD-alternans and SDs, since steady-state APD and global conduction velocity were unchanged under these conditions, and may be unrelated to the associated reduction in whole-cell ICaL. Future studies may clarify potential contributions of local conduction changes, and cellular and sub-cellular mechanisms of alternans, to the increased AF-susceptibility

Contrasted photochromic and luminescent properties in dinuclear Pt(II) complexes linked through a central dithienylethene unit

We disclose two unprecedented complexes built with a central dithienylethene photochrome connecting two cyclometalated Pt(ii) moieties either on the reactive carbon atoms or on the lateral non-reactive carbon atoms of the photochrome. The two systems show vastly different properties that are rationalised thanks to quantum-chemical calculations

Variable Nav1.5 Protein Expression from the Wild-Type Allele Correlates with the Penetrance of Cardiac Conduction Disease in the Scn5a+/− Mouse Model

BACKGROUND: Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects. We investigated the mechanisms of this heterogeneity in a mouse model with heterozygous targeted disruption of Scn5a (Scn5a(+/-) mice) and compared our results to those obtained in patients with loss-of-function mutations in SCN5A. METHODOLOGY/PRINCIPAL FINDINGS: Based on ECG, 10-week-old Scn5a(+/-) mice were divided into 2 subgroups, one displaying severe ventricular conduction defects (QRS interval>18 ms) and one a mild phenotype (QRS53 weeks), ajmaline effect was larger in the severely affected subgroup. These data matched the clinical observations on patients with SCN5A loss-of-function mutations with either severe or mild conduction defects. Ventricular tachycardia developed in 5/10 old severely affected Scn5a(+/-) mice but not in mildly affected ones. Correspondingly, symptomatic SCN5A-mutated Brugada patients had more severe conduction defects than asymptomatic patients. Old severely affected Scn5a(+/-) mice but not mildly affected ones showed extensive cardiac fibrosis. Mildly affected Scn5a(+/-) mice had similar Na(v)1.5 mRNA but higher Na(v)1.5 protein expression, and moderately larger I(Na) current than severely affected Scn5a(+/-) mice. As a consequence, action potential upstroke velocity was more decreased in severely affected Scn5a(+/-) mice than in mildly affected ones. CONCLUSIONS: Scn5a(+/-) mice show similar phenotypic heterogeneity as SCN5A-mutated patients. In Scn5a(+/-) mice, phenotype severity correlates with wild-type Na(v)1.5 protein expression

Linear and nonlinear optical molecular switches based on photochromie metal complexes

International audienceThis chapter is devoted to our works made in the area of photochromie organometallic compounds which can be used for the photomodulation of the quadratic nonlinear optical (NLO) properties and for the photoregulation of the emission properties of the resulting systems. The first part is related to the design of chromophores combining two types of dithienylethene (DTE)-based bipyridine ligands with different metal fragments (Re1, Fe11, Ru11, Ir111, Cu1, Zn11) which give rise to multi-photochromic metal complexes. The photoregulation of their quadratic nonlinear optical (NLO) properties, as well as their luminescence properties, is then discussed. The last part deals with the synthesis, photochromic properties, and NLO-switching behavior of Cyclometallated platinum (II) complexes containing two types of DTE units bound to the metal through an alkynyl linkage. © Springer Japan KK 2017

Access to functionalized luminescent Pt(ii) complexes by photoredox-catalyzed Minisci alkylation of 6-aryl-2,2′-bipyridines

International audiencePhotoredox-mediated C-H bond alkylation of 6-aryl-2,2′-bipyridines withN-(acyloxy)phthalimides is reported. The reaction exhibits excellent functional group tolerance, including chiral aliphatic groups. The influence of the incorporatedC6′-alkyl group on the photophysical properties of the corresponding (N^N^C) cyclometalated Pt(ii) complexes is described, including chiroptical properties

Long Range Charge Separation in a Ferrocene-(Zinc Porphyrin)-Naphthanenediimide Triad with 1,2,3-Triazole Linkers

New dyad and triad systems based on a zinc porphyrin (ZnP), a naphthalenediimide (NDI), and a ferrocene (Fc) as molecular components, linked by 1,2,3-triazole bridges, ZnP-NDI (3) and Fc-ZnP-NDI (4), have been synthesized. Their photophysical behavior has been investigated by both visible excitation of the ZnP chromophore and UV excitation of the NDI unit. Dyad 3 exhibits relatively inefficient quenching of the ZnP singlet excited state, slow charge separation and fast charge recombination processes. Excitation of the NDI chromophore, on the other hand, leads to charge separation by both singlet and triplet quenching pathways, with the singlet charge-separated (CS) state recombining in a sub-ns time scale, and the triplet CS state decaying in ca. 90 ns. In the triad system 4, primary formation of Fc-ZnP+-NDI− charge separated state is followed by a secondary hole shift process from ZnP to Fc. The product of the stepwise charge-separation, Fc+-ZnP-NDI−, undergoes recombination to the ground state, as expected for a long-range process, in a much longer time scale, 1.9 s. The charge separated states are always formed more efficiently upon NDI excitation than upon ZnP excitation. DFT calculations on a bridge-acceptor fragment show that the bridge is expected to mediate a fast donor-to-bridge-to-acceptor electron cascade following excitation of the acceptor. More generally, triazole bridges may behave asymmetrically with respect to photoinduced electron transfer in dyads, kinetically favoring hole-transfer pathways triggered by excitation of the acceptor over electron-transfer pathways promoted by excitation of the donor

A landscape-scale field survey demonstrates the role of wheat volunteers as a local and diversified source of leaf rust inoculum

Abstract Deploying disease-resistant cultivars is one of the most effective control strategies to manage crop diseases such as wheat leaf rust, caused by Puccinia triticina. After harvest, this biotrophic fungal pathogen can survive on wheat volunteers present at landscape scale and constitute a local source of primary inoculum for the next cropping season. In this study, we characterised the diversity of P. triticina populations surveyed on wheat volunteer seedlings for six consecutive years (2007–2012) at the landscape scale. A total of 642 leaf rust samples classified in 52 virulence profiles (pathotypes) were collected within a fixed 5-km radius. The pathotype composition (identity and abundance) of field-collected populations was analyzed according to the distance between the surveyed wheat plots and to the cultivars of origin of isolates. Our study emphasised the high diversity of P. triticina populations on wheat volunteers at the landscape scale. We observed an impact of cultivar of origin on pathogen population composition. Levels of population diversity differed between cultivars and their deployment in the study area. Our results suggest that wheat volunteers could provide a significant though highly variable contribution to the composition of primary inoculum and subsequent initiation of leaf rust epidemics

Hole-Transfer Dyads and Triads Based on Perylene Monoimide, Quaterthiophene, and Extended Tetrathiafulvalene

Two families of dyad and triad systems based on perylene monoimide (PMI), quaterthiophene (QT), and 9,10-bis(1,3-dithiol-2-ylidene)-9,10- dihydroanthracene (extended tetrathiafulvalene, exTTF) molecular components have been designed and synthesized. The dyads (D1 and D2) are of the PMI–QT type and the triads (T1 and T2) of the PMI–QT–exTTF type. The two families differ in the saturated or unsaturated nature of the linker groups (ethynylene in D1 and T1, ethylene in D2 and T2) that bridge the molecular components. The dyads and triads have been characterized by electrochemical, photophysical, and computational methods. Both the experimental and the computational (DFT) results indicate that in the unsaturated systems strong intercomponent interactions lead to substantial perturbation of the properties of the subunits. In particular, in T1, delocalization is particularly effective between the QT and exTTF units, which would be better viewed combined as a single electronic subsystem. For the dyad systems, the photophysics observed following excitation of the PMI unit is solvent-dependent. In moderately polar solvents (dichloromethane, diethyl ether) fast charge separation is followed by recombination to the ground state. In toluene, slow conversion to the chargeseparated state is followed by intersystem crossing and recombination to yield the triplet state of the PMI unit. The behavior of the triads, on the other hand, is remarkably similar to that of the corresponding dyads, which indicates that, after primary charge separation, hole shift from the oxidized QT component to exTTF is quite inefficient. This unexpected result has been rationalized on the basis of the anomalous (simultaneous two-electron oxidation) electrochemistry of exTTF and with the help of DFT calculations. In fact, although exTTF is electrochemically easier to oxidize than QT by around 0.6 V, the one-electron redox orbitals (HOMOs) of the two units in triad T2 are almost degenerate