Calcium release near l-type calcium channels promotes beat-to-beat variability in ventricular myocytes from the chronic AV block dog

Beat-to-beat variability of ventricular repolarization (BVR) has been proposed as a strong predictor of Torsades de Pointes (TdP). BVR is also observed at the myocyte level, and a number of studies have shown the importance of calcium handling in influencing this parameter. The chronic AV block (CAVB) dog is a model of TdP arrhythmia in cardiac hypertrophy, and myocytes from these animals show extensive remodeling, including of Ca^2 + handling. This remodeling process also leads to increased BVR. We aimed to determine the role that (local) Ca^2 + handling plays in BVR.In isolated LV myocytes an exponential relationship was observed between BVR magnitude and action potential duration (APD) at baseline. Inhibition of Ca^2 + release from sarcoplasmic reticulum (SR) with thapsigargin resulted in a reduction of [Ca^2 +]_i, and of both BVR and APD. Increasing I_CaL in the presence of thapsigargin restored APD but BVR remained low. In contrast, increasing I_CaL with preserved Ca^2 + release increased both APD and BVR. Inhibition of Ca^2 + release with caffeine, as with thapsigargin, reduced BVR despite maintained APD. Simultaneous inhibition of Na⁺/Ca^2 + exchange and I_CaL decreased APD and BVR to similar degrees, whilst increasing diastolic Ca^2 +. Buffering of Ca^2 + transients with BAPTA reduced BVR for a given APD to a greater extent than buffering with EGTA, suggesting subsarcolemmal Ca^2 + transients modulated BVR to a larger extent than the cytosolic Ca^2 + transient.In conclusion, BVR in hypertrophied dog myocytes, at any APD, is strongly dependent on SR Ca^2 + release, which may act through modulation of the l-type Ca^2 + current in a subsarcolemmal microdomain.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system

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Outcomes of Percutaneous and Surgical Pulmonary Valve Implantation

BackgroundThe objective of this study is to describe the recent trends and in-hospital outcomes with percutaneous pulmonic valve implantation (PPVI) and surgical pulmonic valve replacement (SPVR) in adult hospitals in the US after the availability of both the Melody valve (Medtronic Inc., Minneapolis, Minnesota) and the Sapien XT valve (Edwards Lifesciences, Irvine, CA).MethodsWe queried the National Inpatient Sample database (NIS) from January 2016 to December 2017 to identify hospitalizations for PPVI and SPVR.ResultsWe identified 5455 weighted discharges with PPVI and SPVR (PPVI=1140, SPVR=4305). PPVI procedures had increased in number over 2016 and 2017 (115 procedure at the first quarter of 2016, 195 procedures in the final quarter of 2017, P-trend=0.086), while SPVR volume remained constant. The incidence of in-hospital mortality was low with both procedures (SPRV: 1.6% vs. PPVI: 0.9%, p=0.071). SPVR had worse in-hospital outcomes, was associated with a longer length of stay [5 days vs. 1 day, p<0.001], and comparable cost of index hospitalization [$51,657 vs. $51,193] compared with PPVI.ConclusionAfter approval of the Sapien valve for commercial use in 2016, PPVI procedures have increased in frequency. PPVI is associated with lower procedural complications than SPVR, however, both carry a low risk of mortality. Despite the higher cost of the valves and delivery systems, PPVI is associated with a slightly lower cost of index hospitalization compared with SPVR, likely due to the higher in-hospital complications and LOS of the latter.