Nowadays, only a few data are available about left heart unloading in V-A ECMO support. Despite the well-known controversy, IABP remains widely used in combination with V-A ECMO. Percutaneous approaches utilizing unloading devices is becoming an increasingly used option. However, further studies are required to establish the optimal LV unloading method.

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Enallagma aspersum and E. traviatum (Odonata: Coenagrionidae) are the most abundant larval odonates in Bays Mountain Park (Sullivan County, Tennessee, USA), although their spatial distributions are essentially nonoverlapping. E. traviatum coexists with insectivorous fish in a small lake, whereas E. aspersum is restricted to a small fishless pond nearby. Behavioral observations revealed that E. aspersum larvae were more active than E. traviatum, and tended to occupy more conspicuous positions. E. aspersum also enganged in more confrontations than E. traviatum, especially at higher density. In laboratory experiments with juvenile bluegills (Lepomis macrochirus) as predators, E. aspersum larvae were more vulnerable to predation than E. traviatum. Red—spotted newts (Notophthalmus viridescens) also preyed on E. aspersum disproportionately. Field enclosure experiments revealed that dry mass of individual E. aspersum larvae was density dependent, and that increased density of E. aspersum or addition of E. traviatum produced similar reductions. Competition was asymmetrical, as E. aspersum appeared to have no significant effect on E. traviatum. The substantial increase in confrontations among E. aspersum larvae at higher density, and the lack of evidence for prey depletion, suggest that interference may be the mechanism of competition. Our results suggest that the distribution of E. aspersum larvae may be limited by fish predation, but although competitive interactions were detected, we have no evidence that larval competition influences the distribution of either species.

Beat-to-beat variability of repolarization duration (BVR) is an intrinsic characteristic of cardiac function and a better marker of proarrhythmia than repolarization prolongation alone. The ionic mechanisms underlying baseline BVR in physiological conditions, its rate dependence, and the factors contributing to increased BVR in pathologies remain incompletely understood. Here, we employed computer modeling to provide novel insights into the subcellular mechanisms of BVR under physiological conditions and during simulated drug-induced repolarization prolongation, mimicking long-QT syndromes type 1, 2, and 3. We developed stochastic implementations of 13 major ionic currents and fluxes in a model of canine ventricular-myocyte electrophysiology. Combined stochastic gating of these components resulted in short- and long-term variability, consistent with experimental data from isolated canine ventricular myocytes. The model indicated that the magnitude of stochastic fluctuations is rate dependent due to the rate dependence of action-potential (AP) duration (APD). This process (the “active” component) and the intrinsic nonlinear relationship between membrane current and APD (“intrinsic component”) contribute to the rate dependence of BVR. We identified a major role in physiological BVR for stochastic gating of the persistent Na+ current (INa) and rapidly activating delayed-rectifier K+ current (IKr). Inhibition of IKr or augmentation of INa significantly increased BVR, whereas subsequent β-adrenergic receptor stimulation reduced it, similar to experimental findings in isolated myocytes. In contrast, β-adrenergic stimulation increased BVR in simulated long-QT syndrome type 1. In addition to stochastic channel gating, AP morphology, APD, and beat-to-beat variations in Ca2+ were found to modulate single-cell BVR. Cell-to-cell coupling decreased BVR and this was more pronounced when a model cell with increased BVR was coupled to a model cell with normal BVR. In conclusion, our results provide new insights into the ionic mechanisms underlying BVR and suggest that BVR reflects multiple potentially proarrhythmic parameters, including increased ion-channel stochasticity, prolonged APD, and abnormal Ca2+ handling.

2+ release (SCR) from the sarcoplasmic reticulum can cause delayed afterdepolarizations and triggered activity, contributing to arrhythmogenesis during β-adrenergic stimulation. Excessive beat-to-beat variability of repolarization duration (BVR) is a proarrhythmic marker. Previous research has shown that BVR is increased during intense β-adrenergic stimulation, leading to SCR.Objective: We aimed to determine ionic mechanisms controlling BVR under these conditions. potential (AP) of the single cardiac myocyte to the QT interval on the body surface. 7-9 Exaggerated BVR has been reported to be a more reliable indicator of arrhythmogenic risk than repolarization prolongation, per se, at least in several experimental ventricular tachycardia models [10][11][12] and in selected human subjects. 8,13 Although BVR has been investigated in multiple studies, the mechanisms underlying this phenomenon at the singlecell level remain to be fully elucidated. Pharmacological interventions influencing ion channels that operate during the AP plateau can markedly alter BVR. 7,14 Despite the fact that inhibition of the slowly activating delayed rectifier K + current (I Ks ) alone has minimal effects on both cellular AP duration (APD) and BVR, 14 we recently have shown that during increased Ca 2+ loading in myocytes subjected to blockade of I Ks in combination with βAR stimulation, BVR is significantly enhanced, even before the occurrence of EADs and TA. 14 In the present study, we investigated the relationship between SCR and BVR using a combined experimental and computational approach in both canine ventricular myocytes and in situ hearts subjected to βAR stimulation. We show that SCRs not only lead to I ti and DAD formation but also lead to a prolonged duration of AP via increased L-type Ca 2+ current (I CaL ), which in turn leads to increased BVR when analyzing multiple consecutive APs. Pharmacological interventions that inhibit SCR (either with reduced or with preserved systolic contraction) prevent this SCR-associated AP prolongation and reduce BVR. Methods and Results: MethodsThis investigation conformed to the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (National Institutes of Health Publication 85-23, revised 1996). Animal handling was in accordance with the European Directive for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (86/609/EU). Full details of methods, solutions, and interventions used are given in the onlineonly Data Supplement accompanying this article. A brief summary of the main aspects is provided. Myocyte Isolation and ElectrophysiologyCanine left ventricular (LV) myocytes were isolated as previously described. 15 Transmembrane APs were recorded at ≈37°C using highresistance (30-60 MΩ) glass microelectrodes filled with 3 mol/L KCl. Myocyte contractions were recorded with a video edge motion detector. Calcium MeasurementWe used the perforated patch-clamp technique under current-clamp or vol...

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ATP, released at the leading edge of migrating neutrophils, amplifies chemotactic signals. The aim of our study was to investigate whether neutrophils express ATP-gated P2X1 ion channels and whether these channels could play a role in chemotaxis. Whole-cell patch clamp experiments showed rapidly desensitizing currents in both human and mouse neutrophils stimulated with P2X1 agonists, αβ-methylene ATP (αβMeATP) and βγMeATP. These currents were strongly impaired or absent in neutrophils from P2X1−/− mice. In Boyden chamber assays, αβMeATP provoked chemokinesis and enhanced formylated peptide- and IL-8-induced chemotaxis of human neutrophils. This agonist similarly increased W-peptide-induced chemotaxis of wild-type mouse neutrophils, whereas it had no effect on P2X1−/− neutrophils. In human as in mouse neutrophils, αβMeATP selectively activated the small RhoGTPase RhoA that caused reversible myosin L chain phosphorylation. Moreover, the αβMeATP-elicited neutrophil movements were prevented by the two Rho kinase inhibitors, Y27632 and H1152. In a gradient of W-peptide, P2X1−/− neutrophils migrated with reduced speed and displayed impaired trailing edge retraction. Finally, neutrophil recruitment in mouse peritoneum upon Escherichia coli injection was enhanced in wild-type mice treated with αβMeATP, whereas it was significantly impaired in the P2X1−/− mice. Thus, activation of P2X1 ion channels by ATP promotes neutrophil chemotaxis, a process involving Rho kinase-dependent actomyosin-mediated contraction at the cell rear. These ion channels may therefore play a significant role in host defense and inflammation.