Abstract Introduction Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload. Methods Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test. Results M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2). Conclusions CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP & RV remodeling

The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex cerebral area involved in processing superior cognitive functions. Most current evidence points to hippocampal oxidative damage as a causal effect for neurodegenerative disorders, especially Alzheimer's disease. Nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) is a master key for the transcriptional regulation of antioxidant and detoxifying systems. It is ubiquitously expressed in brain areas, mainly supporting glial cells. In the present study, we have analyzed the relationships between Nrf2 and Keap1 isoforms in hippocampal tissue in response to aging and dietary long-chain polyunsaturated fatty acids (LCPUFA) supplementation. The possible involvement of lipoxidative and nitrosative by-products in the dynamics of the Nrf2/Keap1 complex was examined though determination of protein adducts, namely malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 3-nitro-tyrosine (NTyr) under basal conditions. The results were correlated to the expression of target proteins heme-oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPx4), whose expressions are known to be regulated by Nrf2/Keap1 signaling activation. All variables in this study were obtained simultaneously from the same preparations, allowing multivariate approaches. The results demonstrate a complex modification of the protein expression patterns together with the formation of adducts in response to aging and diet supplementation. Both parameters exhibited a strong interaction. Noticeably, LCPUFA supplementation to aged animals restored the Nrf2/Keap1/target protein patterns to the status observed in young animals, therefore driving a "rejuvenation" of hippocampal antioxidant defense.

Abstract Background Pulmonary hypertension (PH) includes a wide spectrum of pathologies with different pathological bases and a variety of clinical scenarios in which right ventricular (RV)-pulmonary artery (PA) coupling has relevant prognostic implications. Currently, diagnosis and hemodynamic severity of PH is typically based on mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). However, this conception does not take into consideration the evolution of these parameters throughout the cardiac cycle. We hypothesized that not only the magnitude but also the dynamics over time plays an important role in RV adaptation to pressure overload (i.e., constant fixed resistances throughout the cycle will have a different impact than a fluctuating resistances). Purpose To assess PA hemodynamic patterns throughout the cardiac cycle and their association with RV remodelling, by combining right heart catheterization (RHC) and cardiac magnetic resonance imaging (CMR) data. Methods 66 patients with PH (38 women, aged 63.59±14.70years, BMI 28.49±6.21 kg.m2) who underwent RHC in the supine position with a 7.5-FrSwan-Ganz catheter under fluoroscopic guidance (37 precapillary, 17 combined pre-postcapillary, 12 isolated postcapillary PH) and CMR with flow-encoded phase-contrast sequence were included. Pressure and flow tracings at the level of the main PA were integrated to obtain volume-pressure loops throughout the cardiac cycle. The resulting patterns based on morphology (Image 1) and slope (Pattern 1 mean slope 16,11% vs Pattern 2 mean slope 10,37%) were analysed and classified into 2 groups: Pattern 1 and Pattern 2. RV end-systolic (iRVESV) and end-diastolic volumes (iRVEDV), RV ejection fraction, RV mass and presence of late gadolinium enhancement (LGE) at the RV insertion points were compared between groups using parametric and non-parametric tests. Results Patients with Pattern 1 showed significantly higher mPAP (46.03±11.62 vs. 35.77±8.10 mmHg) and iPVR (746.22±584.54 vs 319.56±306.21 dynes.s.cm-5.m2) and lower PCWP (11.8±7.6 vs 17.7±7.2 mmHg). Precapillary PH patients more frequently presented a Pattern 1 (n=27; 77.1% vs 10; 32.3%). In addition, patients with Pattern 1 had higher RV volumes (iRVEDV= 105.45±34.62 ml/m2 vs 84.22±35.0 ml/m2, p=0,002; iRVESV 65.05±27.59 ml/m2 vs 44.63±25.09 ml/m2, p=0,001), poorer RV function (RVEF 39.81±11.33% vs 48.96±10.90%; p=0,001), larger RV mass (27.95±9.46 vs 23,44±7.46 g/m2, p=0,045) and smaller left atrial size (24.18±11.47 vs 34.06±19.15 cm2, p<0,001) than patients with Pattern 2. The quantification of LGE was also higher in Pattern 1 as compared with Pattern 2 (5.4±2.4% vs 3.0±2.3%, p<0.001). Conclusion Volume-pressure loops at the level of the main PA may differentiate patterns of PA hemodynamic fluctuations that have different impact on RV performance regardless the PH severity within the wide spectrum of PH.Volume-pressure loop patterns

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value <0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p<0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p<0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p<0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p<0.000). In the subgroup of patients with moderate-severe LV hypertrophy (<17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p<0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

"Lipid raft aging" in nerve cells represents an early event in the development of aging-related neurodegenerative diseases, such as Alzheimer's disease. Lipid rafts are key elements in synaptic plasticity, and their modification with aging alters interactions and distribution of signaling molecules, such as glutamate receptors and ion channels involved in memory formation, eventually leading to cognitive decline. In the present study, we have analyzed, in vivo, the effects of dietary supplementation of n-3 LCPUFA on the lipid structure, membrane microviscosity, domain organization, and partitioning of ionotropic and metabotropic glutamate receptors in hippocampal lipid raffs in female mice. The results revealed several lipid signatures of "lipid rafts aging" in old mice fed control diets, consisting in depletion of n-3 LCPUFA, membrane unsaturation, along with increased levels of saturates, plasmalogens, and sterol esters, as well as altered lipid relevant indexes. These changes were paralleled by increased microviscosity and changes in the raft/non-raft (R/NR) distribution of AMPA-R and mGluR5. Administration of the n-3 LCPUFA diet caused the partial reversion of fatty acid alterations found in aged mice and returned membrane microviscosity to values found in young animals. Paralleling these findings, lipid rafts accumulated mGluR5, NMDA-R, and ASIC2, and increased their R/NR proportions, which collectively indicate changes in synaptic plasticity. Unexpectedly, this diet also modified the lipidome and dimension of lipid rafts, as well as the domain redistribution of glutamate receptors and acid-sensing ion channels involved in hippocampal synaptic plasticity, likely modulating functionality of lipid rafts in memory formation and reluctance to age-associated cognitive decline.

Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts’ integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice’s hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by “rejuvenating” the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains.

Objective To describe the short-term fetal hemodynamic response and early adaptation to an artificial placenta (AP) system. Methods Experimental study in 6 fetal lambs (105-115 days) transferred to an AP system (pumpless circuit with umbilical cord connection and low resistance oxygenator). Arterial and venous intravascular pressures were monitorized via femoral artery and umbilical vein catheters. Echocardiographic-derived anatomical and functional measurements were collected at baseline (in utero), 30 mins and 2-6 hours after connection. Transition to AP resulted in increased peak velocities and reduced pulsatility index of the umbilical artery: in utero median 1.26 (IQR 1.1-1.48) vs. 30min 0.42 (0.34-0.52) vs 2-6h 0.42 (0.36-0.45), p=0.004) and ductus venosus, together with increased arterial and venous pressures (mean arterial pressure in utero 44 mmHg (35-54) vs. 30min 72 mmHg (64-80) vs. 2-6h 56 mmHg (50-70), p=0.007) and increased fetal heart rate (in utero 144 bpm (141-157) vs. 30min 198 bpm (176-222) vs. 2-6h 175 bpm (165-190), p=0.004). Fetal heart structure and function was mainly preserved (combined cardiac output in utero 452 ml/kg/min (431-502) vs. 30min 495 ml/kg/min (450-632) vs. 2-6h 447 ml/kg/min (446-459), p=0.337). AP results in an acute response that may partially reflect fetal stress with adaptation to a low resistant circuit, and which tends to normalize over hours. Longer-term data will help understanding the fetal cardiovascular adaptive response and potential remodeling, and help refining the extracorporeal circulation settings accordingly.

Purpose Acquired von Willebrand disease (aVWD) is not uncommon during long-term mechanical circulatory support. However, its development during short-term support is unknown. We aim at investigating the development of aVWD in patients under extracorporeal life support (ECLS) and its potential treatment. Methods Patients who received ECLS in our center since June 2020 were included (25). Primary hemostasis was evaluated by: VWF antigen (VWF:Ag) and activity (VWF:GPIbM) measurement (immunoturbidimetry), VWF multimers analysis (agarose-gels and immunoblotting), platelet aggregation by ristocetin (turbidimetry), platelet functional analysis (PFA-200) -collagen/epinephrine (Col/EPI) and collagen/ADP (Col/ADP) cartridges-, and platelet activation (flow cytometry analysis of P-selectin and Lisosomal antigen). Studies were performed the day after implant and 3 days after explant. T-TAS was applied in bleeding patients, using samples before and after in vitro addition of purified VWF. Results At day 1 day after implant, all patients showed increased VWF:Ag. In 15 (60%) there was an altered ratio (<0.7) between VWF:GPIbM and VWF:Ag, with loss of VWF high molecular weight multimers (HMWM). In all cases, prolonged occlusion times at the PFA with both cartridges were observed. A significant increased expression of platelet-activation antigens was detected in 5 patients (11% and 24% for P-Selectin and Lysosomal antigen, respectively, vs. control platelets). In bleeding patients, addition of purified VWF to blood samples reduced significantly (p<0.05) the occlusion time (-384s) and increased the AUW (370%) at T-TAS. All patients that survived to explant (16) showed normalization of VWF:GPIbM/VWF:Ag ratio (>0.7) and multimers, with reduction of PFA-200 values. Conclusion ECLS caused primary hemostasis alterations, leading to aVWD and platelet activation, independently of platelet counts. Hemostatic efficiency in bleeding patients can be corrected by purified VWF, as derived from the in vitro evidence. The primary hemostasis alteration observed was solved early after support removal.

Purpose Infections remains a significant cause of death in short-term MCS patients. There is controversy regarding the indication and duration of antimicrobial (ATB) prophylaxis. We aimed to review our most recent experience and the impact of patient origin on the infection rate and prevalence of MDR bacterial (multi-resistant) colonization. Methods An observational retrospective study was conducted of all consecutive short-term support devices implanted inside a tertiary university hospital from 2014 - 2020 (n=57). Infection rate, clinical characteristics of infections, duration and type of AB prophylaxis, and prevalence of MDR bacterial colonization were recorded. As a secondary analysis, patients were divided into two groups according to the length of admission before support was initiated: Community acquired infections, when MCS was implanted less than three days from hospital admission (CO n=22) and Hospital-acquired infections, in patients with MCS implanted more than three days from hospital admission (H n=35). Results Fifty-seven patients were included, of which 77,2% were male. Medium age at implant was 54,3 years (SD 14 years). The most common etiology was ischemic heart disease, and the median LVEF was 20%. 95% of patients were on preoperative inotropes, and 38,6% were on ECLS support. 84,21% were intubated, and 47,36% were on renal replacement therapy.100% of patients received antibiotic prophylaxis, all covered gram-negative rods and gram-positive cocci including MRSA. Duration varied between 1 and 20 days. After classifying patients according to their preoperative length of stay, we found that in H patients infections were more frequent than in CO patients. The rate of MDR was also higher in the first group. It is noteworthy that all sternal infections happened after transplant and that in the Hospital-acquired group, sternal infections were fungal. There were no differences in survival. Conclusion There were no differences in antibiotic prophylaxis depending on the preimplant LOS. Most infections occurred once support had been removed and were more frequent after heart transplant. Mediastinitis is a rare complication, but post-transplant fungal infections may appear despite adequate antifungal prophylaxis. Further clinical studies are needed to reduce the risk of infection in short-term MCS patients.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 ( n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91–98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Abstract Background Heart transplant (HT) remains the last treatment option for patients with non-obstructive hypertrophic cardiomyopathy (HCM) who develop end-stage heart failure (HF). Early identification of patients who may require a HT in the future is crucial in order to advise them, establish the appropriate follow-up and determine the appropriate time to include them in the waiting list. Objectives Our study sought to find predictive factors related with requiring HT during follow-up in patients with HCM. Methods Consecutive patients with HCM referred to a HCM monographic clinic from 2018 to 2020 (HCM controls) and transplanted patients due to HCM in the same tertiary HT hospital since 2003 (cases) were included. Baseline (on the date of HCM diagnosis) and longitudinal data regarding clinical, genetic, ECG and echocardiographic variables were retrospectively evaluated. Follow-up was registered from HCM diagnosis to HT (in cases) or last medical check up (controls). Results A total of 157 patients (24 HCM-HT cases and 133 HCM controls) were included (45±19 yo; 57% male). At the time of MCH diagnosis (Table), cases were significantly younger than controls, were more frequently symptomatic and showed significantly higher BNP levels and more advanced diastolic dysfunction (larger left atrium, higher E/A ratio and lower e'); also, HCM-HT reported more family history and had higher proportion of pathogenic mutations (being MYH7 the most frequently involved). Left ventricular (LV) systolic function was slightly reduced in HCM-HT cases. In contrast, HCM controls were more frequently diagnosed by casual findings or family screening and had more LV outflow tract obstruction at first medical evaluation. LV maximal wall thickness (MWT) did not differ between groups. During a median follow-up since HCM diagnosis of 6.2 years (median follow-up of 8.9 and 7.1 years in cases and controls, respectively), HCM-HT cases presented a higher incidence of sustained ventricular tachycardia or ICD therapy (HR=4.0; CI95%:1.6–10.0 p=0.03) and HF admissions (HR=3.9; CI95%:1.8–8.1 p<0.001). There were no cardiovascular deaths during follow-up. Conclusions The presence of symptoms in a young non-obstructive HCM patient, along with family history and a pathogenic mutation, should advice clinicians a closer follow-up and early transfer to a HT referral center, especially if associated with diastolic dysfunction and high BNP values. Funding Acknowledgement Type of funding sources: None. Table 1

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 European Commission Project H2020-MSCA-ITN-2016 (764738) and the Clinical Research in Cardiology grant from the Spanish Cardiac Society. Background The aetiology of left ventricular hypertrophy (LVH) is a relevant clinical challenge with consequences for patient management. Phenotypes resulting from hypertensive remodelling and sarcomere mutation often overlap. Synchrotron X-ray phase-contrast imaging (X-PCI) is a technique that can provide 3-dimensional detailed information on myocardial micro-structure non-destructively. The aim is to relate macrostructural/functional, non-invasive, imaging phenotypes of hypertrophic cardiomyopathy (HCM) to the underlying myocardial microstructure assessed with X-PCI. Methods Myocardial tissue samples were obtained from three patients (P1-3) with obstructive myocardial hypertrophy undergoing septal myectomy. Medical history and the 5-year HCM risk scores were evaluated. The patients were imaged with magnetic resonance imaging and echocardiography prior to procedure. Myocardial structure was assessed with wall thickness, late gadolinium enhancement (LGE), whereas function with speckle-tracking deformation (STE) and tissue Doppler imaging (TDI). Myectomy tissue was imaged with X-PCI in the TOMCAT beamline, using a multiscale propagation-based protocol combining a low-resolution (LR) and a high-resolution (HR) setup (5.8 and 0.7 um pixel size, respectively). Results The clinical and imaging data are shown in Fig 1. On initial assessment, wall thickness, LGE distribution, global longitudinal strain and septal TDI demonstrated a similar macrostructural and functional phenotype of P1 and P2, whereas P3 stood out with more severe hypertrophy, scarring and dysfunction. Additional regional deformation analysis with STE revealed reduced deformation in the basal and mid septum in P1, paired with a hypertensive pattern of post-systolic shortening (PSS) (yellow arrows). In comparison, in P2 and P3, deformation was more heterogeneous regionally, with regions of almost complete absence of deformation (orange arrows). Upon further exploration with TDI, areas with abnormal deformation were identified on the transition from basal to mid septum in both P2 and P3, whereas deformation was normal, but reduced in P1, and paired with PSS. LR X-PCI defined regions of interest to scan with HR (yellow frame), where HR revealed extensive interstitial fibrosis (orange arrow) with normal myocyte size and organisation in P1, compatible with severe hypertensive remodelling. However, in P2 and P3, patches of fibrosis (yellow arrow) paired with enlarged myocytes organized in visible disarray, considerably more prominent in P3, were both compatible with sarcomere-mutation HCM. Conclusion The results demonstrate multiscale phenotyping of HCM - relating micro- and macrostructural findings to function, and integrating multimodality data. In-depth regional deformation analysis, validated by synchrotron-based microstructural analysis, showed potential to identify distinct imaging phenotypes in HCM, distinguishing between overlapping presentations in different aetiologies. Abstract Figure 1

Chronic stress produces long-term metabolic changes throughout the superfamily of nuclear receptors, potentially causing various pathologies. Sex hormones modulate the stress response and generate a sex-specific age-dependent metabolic imprint, especially distinct in the reproductive senescence of females. We monitored chronic stress recovery in two age groups of female Sprague Dawley rats to determine whether stress and/or aging structurally changed the glycolipid microenvironment, a milieu playing an important role in cognitive functions. Old females experienced memory impairment even at basal conditions, which was additionally amplified by stress. On the other hand, the memory of young females was not disrupted. Stress recovery was followed by a microglial decrease and an increase in astrocyte count in the hippocampal immune system. Since dysfunction of the brain immune system could contribute to disturbed synaptogenesis, we analyzed neuroplastin expression and the lipid environment. Neuroplastin microenvironments were explored by analyzing immunofluorescent stainings using a newly developed Python script method. Stress reorganized glycolipid microenvironment in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) hippocampal regions of old females but in a very different fashion, thus affecting neuroplasticity. The postulation of four possible neuroplastin environments pointed to the GD1a ganglioside enrichment during reproductive senescence of stressed females, as well as its high dispersion in both regions and to GD1a and GM1 loss in the CA1 region. A specific lipid environment might influence neuroplastin functionality and underlie synaptic dysfunction triggered by a combination of aging and chronic stress.

Patients mechanically supported showed higher preoperative use of inotropes (96,2% vs.22%, p<0,001), orotracheal intubation (88,46% vs.4% p <0,001) and renal dysfunction (30,8% vs.4%, p<0,001). Pre-transplant use of pulmonary vasodilators (7,7% vs.30%; p=0,02) and ACEIs was higher in the non-supported group (3,8%vs.49%, p<0,001). There was no difference in the incidence of post-transplant vasoplegia (26,9% vs.27%, p=0,99). Perioperative mortality (at discharge) was higher in the supported group (12% vs. 1% p=0,196) but it was not different regarding the incidence of vasoplegia (3,3% vs. 2,8% p= 1,0) CONCLUSION: Post-transplant vasoplegia was not influenced by the preoperative use of short-term mechanical circulatory support devices and was not associated with increased mortality in our series.

Abstract INTRODUCTION Isolated pulmonary endocarditis is a rare entity, especially in patients without predisposing factors, being its current incidence less than 1% of the total cases of infectious endocarditis. This is due to the lower right heart pressures and a decrease of intravenous drug-consum, being most of the cases nowadays, related to congenital right-heart diseases or pacemakers and defibrillators implants. CLINICAL CASE A 35 year-old man, tobacco smoker and intravenous cocaine consumer since he was 25, was admitted to our Emergency Department for fever up to 40ºC, cough and dyspnea started three days before admission. In the anamnesis he refereed intravenous consum of cocaine and sharing of syringes the last week. On physical examination he was tachycardic and signs of heart right failure were present such as jugular ingurgitation and peripheral edema. No murmurs were heard. No respiratory failure was detected at any time. Blood test analysis showed high levels of protein C reactive and leukocytosis. Blood cultures were positive for S. aureus (OXA-S) in the first 24h. Chest X-ray (image 1) showed a necrotizing bilateral pneumonia that was confirmed with the presence of cavitated images in the pulmonary CT (image 2). Antibiotic treatment was started with daptomicine + cloxaciline. With the suspicion of right endocarditis a transthoracic echocardiography was performed, showing the presence of a big vegetation (4x1cm) on the pulmonary valve that caused moderate pulmonary insufficiency (images 3, 4). Neither tricuspid nor left side valves were involved. Biventricular function was conserved and hyperdynamic. Endocarditis diagnosis was definitive and due to the presence of multiple right embolisms and the big size of the vegetation, the patient underwent cardiac surgery. Intra-surgical finding demonstrated a big vegetation of almost 5 cm (image 5) depending of the posterior pulmonary valve that was removed; the posterior valve needed to be repaired. Posterior clinical evolution was correct without complications, completing 17 days of i.v. antibiotics (cloxaciline) before discharge. CONCLUSIONS Right endocarditis is a rapidly progressive disease due to the fact that staphylococcus are the most frequent microorganisms involved. Valvular destruction and secondary embolic phenomena are the rule. Tricuspid valve is involved most of the times being the isolated pulmonary valve affection very uncommon. Abstract 474 Figure. CT, Echo and surgical images