AimsThe EMPA‐REG OUTCOME study showed reduced mortality and hospitalization due to heart failure (HF) in diabetic patients treated with empagliflozin. Overexpression and Ca2+‐dependent activation of Ca2+/calmodulin‐dependent kinase II (CaMKII) are hallmarks of HF, leading to contractile dysfunction and arrhythmias. We tested whether empagliflozin reduces CaMKII‐ activity and improves Ca2+‐handling in human and murine ventricular myocytes.Methods and resultsMyocytes from wild‐type mice, mice with transverse aortic constriction (TAC) as a model of HF, and human failing ventricular myocytes were exposed to empagliflozin (1 μmol/L) or vehicle. CaMKII activity was assessed by CaMKII–histone deacetylase pulldown assay. Ca2+ spark frequency (CaSpF) as a measure of sarcoplasmic reticulum (SR) Ca2+ leak was investigated by confocal microscopy. [Na+]i was measured using Na+/Ca2+‐exchanger (NCX) currents (whole‐cell patch clamp). Compared with vehicle, 24 h empagliflozin exposure of murine myocytes reduced CaMKII activity (1.6 ± 0.7 vs. 4.2 ± 0.9, P < 0.05, n = 10 mice), and also CaMKII‐dependent ryanodine receptor phosphorylation (0.8 ± 0.1 vs. 1.0 ± 0.1, P < 0.05, n = 11 mice), with similar results upon TAC. In murine myocytes, empagliflozin reduced CaSpF (TAC: 1.7 ± 0.3 vs. 2.5 ± 0.4 1/100 μm−1 s−1, P < 0.05, n = 4 mice) but increased SR Ca2+ load and Ca2+ transient amplitude. Importantly, empagliflozin also significantly reduced CaSpF in human failing ventricular myocytes (1 ± 0.2 vs. 3.3 ± 0.9, P < 0.05, n = 4 patients), while Ca2+ transient amplitude was increased (F/F0: 0.53 ± 0.05 vs. 0.36 ± 0.02, P < 0.05, n = 3 patients). In contrast, 30 min exposure with empagliflozin did not affect CaMKII activity nor Ca2+‐handling but significantly reduced [Na+]i.ConclusionsWe show for the first time that empagliflozin reduces CaMKII activity and CaMKII‐dependent SR Ca2+ leak. Reduced Ca2+ leak and improved Ca2+ transients may contribute to the beneficial effects of empagliflozin in HF.

BackgroundToday, prehospital emergency medical teams (EMTs) are confronted with emergent situations of cardiac arrest in palliative care patients. However, little is known about the out-of-hospital approach in this situation and the long-term survival rate of this specific patient type. The aim of the present investigation was to provide information about the strategic and therapeutic approach employed by EMTs in outpatient palliative care patients in cardiac arrest.MethodsDuring a period of 2 years, we retrolectively analysed emergency medical calls with regard to palliative care emergency situations dealing with cardiac arrest. We evaluated the numbers of patients who were resuscitated, the prevalence of an advance directive or other end-of-life protocol, the first responder on cardiac arrest, the return of spontaneous circulation (ROSC) and the survival rate.ResultsEighty-eight palliative care patients in cardiac arrest were analysed. In 19 patients (22%), no resuscitation was started. Paramedics and prehospital emergency physicians began resuscitation in 61 cases (69%) and in 8 cases (9%), respectively. A total of 10 patients (11%) showed a ROSC; none survived after 48 h. Advance directives were available in 43% of cases. The start of resuscitation was independent of the presence of an advance directive or other end-of-life protocol.ConclusionsStrategic and therapeutic approaches in outpatient palliative care patients with cardiac arrest differ depending on medical qualification. Although many of these patients do not wish to be resuscitated, resuscitation was started independent of the presence of advance directive. To reduce legal insecurity and to avoid resuscitation and a possible lengthening of the dying process, advance directives and/or “Do not attempt resuscitation” orders should be more readily available and should be adhered to more closely.

These data show that the effects of lipid infusion on LA-induced cardiac arrest are strongly dependent on the administered LAs itself. We conclude that lipophilicity of LAs has a marked impact on the efficacy of lipid infusions to treat cardiac arrest induced by these drugs.

Neuronal Ca2+ oscillations mediate neuronal differentiation and synaptogenesis via activating CaMKII. By acting via the NMDA receptor, S(+)-ketamine exerts its toxic effect through the suppression of neuronal Ca2+ oscillations, down-regulation of the CaMKII, and consecutively reduced synaptic integrity.

Cytoreductive surgery in combination with HITHOC can be performed with acceptable morbidity and mortality rates in selected patients. Patients should be evaluated by an interdisciplinary team to determine their eligibility for this therapeutic alternative. Early clinical results may encourage the use of this surgical option to provide better local tumour control in a multimodality treatment setting.

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The authors demonstrate lipid rescue on the single-cell level and provide evidence for a lipid-sink mechanism.

Veno-venous extracorporeal membrane oxygenation (vvECMO) conventionally requires the cannulation of two vessels. Here we report our initial experience with the "Wang-Zwische" (WZ) double-lumen cannula. In a group of n = 36 patients single venous cannulation for vvECMO was performed. A retrospective analysis was executed. A comparison of flow characteristics to standard two-vessel cannulation was performed. Mean age of the patient population was 48 ± 15 years (body mass index [BMI] 32 ± 13 kg/m(2)). In n = 32 patients (89%) the cannula was implanted percutaneously under echo or fluoroscopic guidance in less than 30 minutes. Nine patients were partially mobilized on extracorporeal membrane oxygenation (ECMO) support. Oxygenation (partial arterial oxygen tension [PaO(2)]/fraction of inspired oxygen [FiO(2)]) improved significantly in all patients from 66 mm Hg (interquartile range [IQR] 58-87 mm Hg) before ECMO to 117 mm Hg (IQR 95-195 mm Hg, p = 0.001) after 24 hours. In seven patients (19%) nonfatal adverse events occurred, including three dislocations, two partial cannula thrombosis, one ventricular perforation, and one retroperitoneal hemorrhage. The negative pressures for drainage at a flow of 2.5 L/min were significantly lower in a standard (S) two-vessel approach compared with a WZ approach (S: -9 mm Hg; IQR -3 to -24 mm Hg, vs. WZ: -23 mm Hg; IQR -4 to -40 mm Hg; p = 0.04). The WZ cannula offers sufficient gas exchange in addition to certain advantages over standard cannulation, including facilitated cannulation in selected patients and improved mobilization.