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Background Identifying new therapeutic targets for preventing the myocardial ischemia–reperfusion injury would have profound implications in cardiovascular medicine. Myocardial ischemia–reperfusion injury remains a major clinical burden in patients with coronary artery disease. Methods and Results We studied several key mechanistic pathways known to mediate cardioprotection in myocardial ischemia–reperfusion in 2 independent genetic models with reduced cardiac phosphoinositide 3‐kinase‐α (PI3Kα) activity. P3Kα‐deficient genetic models (PI3KαDN and PI3Kα‐Mer‐Cre‐Mer) showed profound resistance to myocardial ischemia–reperfusion injury. In an ex vivo reperfusion protocol, PI3Kα‐deficient hearts had an 80% recovery of function compared with ≈10% recovery in the wild‐type. Using an in vivo reperfusion protocol, PI3Kα‐deficient hearts showed a 40% reduction in infarct size compared with wild‐type hearts. Lack of PI3Kα increased late Na+ current, generating an influx of Na+, facilitating the lowering of mitochondrial Ca2+, thereby maintaining mitochondrial membrane potential and oxidative phosphorylation. Consistent with these functional differences, mitochondrial structure in PI3Kα‐deficient hearts was preserved following ischemia–reperfusion injury. Computer modeling predicted that PIP3, the product of PI3Kα action, can interact with the murine and human NaV1.5 channels binding to the hydrophobic pocket below the selectivity filter and occluding the channel. Conclusions Loss of PI3Kα protects from global ischemic–reperfusion injury linked to improved mitochondrial structure and function associated with increased late Na+ current. Our results strongly support enhancement of mitochondrial function as a therapeutic strategy to minimize ischemia–reperfusion injury.

This work proposes a new Pumped Thermal Energy Storage (PTES) configuration that works with supercritical CO2 as the working fluid and molten salts as the thermal storage fluid. The net work generated by this novel proposal is 12.46 MW in the load and 10 MW in the discharge, reaching an efficiency of 80.26%. In addition, a techno-economic optimization is carried out to quantify the discounted cost per unit of energy discharged from this storage technology with a value of 0.116 €/kWh. This technology places this technology as a strong candidate for the future energy solution due to its low wear per duty cycle and easy power scalability. It presents a lower initial cost than other technologies with low LCOS.

ObjectiveMetabolites derived from N−3 and N−6 polyunsaturated fatty acids (PUFAs) have both beneficial and detrimental effects on the heart. However, contribution of these lipid mediators to dilated cardiomyopathy (DCM)-associated mitochondrial dysfunction remains unknown. This study aimed to characterize DCM-specific alterations in the PUFA metabolome in conjunction with cardiac mitochondrial quality in human explanted heart tissues.MethodsLeft ventricular tissues obtained from non-failing control (NFC) or DCM explanted hearts, were assessed for N−3 and N−6 PUFA metabolite levels using LC-MS/MS. mRNA and protein expression of CYP2J2, CYP2C8 and epoxide hydrolase enzymes involved in N−3 and N−6 PUFA metabolism were quantified. Cardiac mitochondrial quality was assessed by transmission electron microscopy, measurement of respiratory chain complex activities and oxygen consumption (respiratory control ratio, RCR) during ADP-stimulated ATP production.ResultsFormation of cardioprotective CYP-derived lipid mediators, epoxy fatty acids (EpFAs), and their corresponding diols were enhanced in DCM hearts. These findings were corroborated by increased expression of CYP2J2 and CYP2C8 enzymes, as well as microsomal and soluble epoxide hydrolase enzymes, suggesting enhanced metabolic flux and EpFA substrate turnover. DCM hearts demonstrated marked damage to mitochondrial ultrastructure and attenuated mitochondrial function. Incubation of fresh DCM cardiac fibers with the protective EpFA, 19,20-EDP, significantly improved mitochondrial function.ConclusionsThe current study demonstrates that increased expressions of CYP-epoxygenase enzymes and epoxide hydrolases in the DCM heart correspond with enhanced PUFA-derived EpFA turnover. This is accompanied by severe mitochondrial functional impairment which can be rescued by the administration of exogenous EpFAs.

In this work, an evaluation and quantification of the impact of using mixtures based on supercritical carbon dioxide “s-CO2” (s-CO2/COS, s-CO2/H2S, s-CO2/NH3, s-CO2/SO2) are made as a working fluid in simple and complex recompression Brayton s-CO2 power cycle configurations that have pressure drops in their components. These cycles are coupled with a solar thermal plant with parabolic-trough collector (PTC) technology. The methodology used in the calculation performance is to establish values of the heat recuperator total conductance (UAtotal) between 5 and 25 MW/K. The main conclusion of this work is that the cycle’s efficiency has improved due to using s-CO2 mixtures as working fluid; this is significant compared to the results obtained using the standard fluid (pure s-CO2). Furthermore, a techno-economic analysis is carried out that compares each configuration’s costs using pure s-CO2 and a mixture of s-CO2/COS with a molar fraction (70/30), respectively, as working fluid where relevant results are obtained. These results show that the best configuration in terms of thermal efficiency and cost is the RCC-RH for pure sCO2 with values of 41.25% and 2811 $/kWe, while for the mixture sCO2/COS, the RCC-2RH configuration with values of 45.05% and 2621 $/kWe is optimal. Using the mixture costs 6.75% less than if it is used the standard fluid (s-CO2).