Isomelezitose Overproduction by Alginate-Entrapped Recombinant E. coli Cells and In Vitro Evaluation of Its Potential Prebiotic Effect.

In this work, the trisaccharide isomelezitose was overproduced from sucrose using a biocatalyst based on immobilized Escherichia coli cells harbouring the α-glucosidase from the yeast Metschnikowia reukaufii, the best native producer of this sugar described to date. The overall process for isomelezitose production and purification was performed in three simple steps: (i) oligosaccharides synthesis by alginate-entrapped E. coli; (ii) elimination of monosaccharides (glucose and fructose) using alginate-entrapped Komagataella phaffii cells; and (iii) semi-preparative high performance liquid chromatography under isocratic conditions. As result, approximately 2.15 g of isomelezitose (purity exceeding 95%) was obtained from 15 g of sucrose. The potential prebiotic effect of this sugar on probiotic bacteria (Lactobacillus casei, Lactobacillus rhamnosus and Enterococcus faecium) was analysed using in vitro assays for the first time. The growth of all probiotic bacteria cultures supplemented with isomelezitose was significantly improved and was similar to that of cultures supplemented with a commercial mixture of fructo-oligosaccharides. In addition, when isomelezitose was added to the bacteria cultures, the production of organic acids (mainly butyrate) was significantly promoted. Therefore, these results confirm that isomelezitose is a potential novel prebiotic that could be included in healthier foodstuffs designed for human gastrointestinal balance maintenance.

Molecular characterization and heterologous expression of two α-glucosidases from Metschnikowia spp, both producers of honey sugars.

BACKGROUND: α-Glucosidases are widely distributed enzymes with a varied substrate specificity that are traditionally used in biotechnological industries based on oligo- and polysaccharides as starting materials. According to amino acid sequence homology, α-glucosidases are included into two major families, GH13 and GH31. The members of family GH13 contain several α-glucosidases with confirmed hydrolytic activity on sucrose. Previously, a sucrose splitting activity from the nectar colonizing yeast Metschnikowia reukaufii which produced rare sugars with α-(1→1), α-(1→3) and α-(1→6) glycosidic linkages from sucrose was described. RESULTS: In this study, genes codifying for α-glucosidases from the nectaries yeast M. gruessii and M. reukaufii were characterised and heterologously expressed in Escherichia coli for the first time. Recombinant proteins (Mg-αGlu and Mr-αGlu) were purified and biochemically analysed. Both enzymes mainly displayed hydrolytic activity towards sucrose, maltose and p-nitrophenyl-α-D-glucopyranoside. Structural analysis of these proteins allowed the identification of common features from the α-amylase family, in particular from glycoside hydrolases that belong to family GH13. The three acidic residues comprising the catalytic triad were identified and their relevance for the protein hydrolytic mechanism confirmed by site-directed mutagenesis. Recombinant enzymes produced oligosaccharides naturally present in honey employing sucrose as initial substrate and gave rise to mixtures with the same products profile (isomelezitose, trehalulose, erlose, melezitose, theanderose and esculose) previously obtained with M. reukaufii cell extracts. Furthermore, the same enzymatic activity was detected with its orthologous Mg-αGlu from M. gruessii. Interestingly, the isomelezitose amounts obtained in reactions mediated by the recombinant proteins, ~ 170 g/L, were the highest reported so far. CONCLUSIONS: Mg/Mr-αGlu were heterologously overproduced and their biochemical and structural characteristics analysed. The recombinant α-glucosidases displayed excellent properties in terms of mild reaction conditions, in addition to pH and thermal stability. Besides, the enzymes produced a rare mixture of hetero-gluco-oligosaccharides by transglucosylation, mainly isomelezitose and trehalulose. These compounds are natural constituents of honey which purification from this natural source is quite unviable, what make these enzymes very interesting for the biotechnological industry. Finally, it should be remarked that these sugars have potential applications as food additives due to their suitable sweetness, viscosity and humectant capacity.

Early Transthoracic Echocardiography after Cardiac Surgery Predicts Postoperative Atrial Fibrillation.

PURPOSE: Postoperative atrial fibrillation (POAF) is frequent after cardiac surgery. We aimed to establish a predictive model of POAF based on postoperative transthoracic echocardiography (TTE) findings. METHODS: This study included 147 patients (aged 67 ± 11 years; 109 men) undergoing coronary artery bypass grafting and/or aortic valve replacement. TTE and Doppler tissue imaging were performed on intensive care unit arrival after surgery. All patients were continuously monitored during hospitalization. The end point was the appearance of POAF. RESULTS: POAF appeared in 37 patients (25.2%). These patients were older (69 ± 16 vs. 65 ± 12 years; P < 0.001) and had increased long axis of the left atrium (LA) dimension (5.4 ± 1 vs. 4.8 ± 0.9 cm, P = 0.02), lower early diastolic velocity of the mitral annulus (e') (6.9 ± 2.1 vs. 8 ± 1.8 cm/sec; P < 0.01), and higher early diastolic pulsed Doppler mitral ratio (E)/e' (E/e') (17.4 ± 6.8 vs. 13.8 ± 6; P = 0.01). Left ventricle diastolic dysfunction grade (DFG) of 2 or 3 relative to grade 0 was significant: odds ratio (OR) 22.5, 95% confidence interval (CI) 4.52-57.2; P < 0.001, and OR: 23.6, 95% CI: 3.57-60.1; P = 0.001), respectively. On multivariate analysis, the independent predictors of POAF were age (OR: 1.10, 95% CI: 1.01-1.18; P < 0.05), long-axis LA dimension (OR: 6.24, 95% CI: 1.97-8.23; P = 0.0017), DFG-2 (OR: 4.1, 95% CI: 1.57-15.81; P < 0.001), and DFG-3 (OR: 8.3, 95% CI: 4.11-25.37; P < 0.001). CONCLUSIONS: Apart from age, the simple determination by postoperative TTE of long-axis LA dimension and DFG after cardiac surgery proved to be powerful independent predictors of POAF and may be useful for risk stratification of these patients.

Rationale and design of a randomized, double-blind, placebo controlled multicenter trial to study efficacy, security, and long term effects of intermittent repeated levosimendan administration in patients with advanced heart failure: LAICA study.

BACKGROUND: Advanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation. METHODS: The LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 µg/kg/min dose, without a loading dose, every 30 days, or placebo. RESULTS: The main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events. CONCLUSIONS: The LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period: The multinational randomized LeoDOR trial.

AIM: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF). METHODS AND RESULTS: In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 µg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 µg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12-7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87-3.11; p = 0.122). CONCLUSIONS: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability.

Diastolic Mitral Regurgitation as a Rare Cause of Acute Respiratory Failure Following Complete Atrioventricular Block.

A 77-year-old male presented to the emergency department with dyspnea. A third-degree atrioventricular block was present in the electrocardiogram and an echocardiography showed a moderate mitral regurgitation with a diastolic functional insufficiency. Hemodynamic variations were assessed in the context of heart rhythm disturbances. (Level of Difficulty: Intermediate.).

Cardiogenic shock code 2023. Expert document for a multidisciplinary organization that allows quality care.

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS.

Ultrasound Assessment in Cardiogenic Shock Weaning: A Review of the State of the Art.

Cardiogenic shock (CS) is associated with a high in-hospital mortality despite the achieved advances in diagnosis and management. Invasive mechanical ventilation and circulatory support constitute the highest step in cardiogenic shock therapy. Once established, taking the decision of weaning from such support is challenging. Intensive care unit (ICU) bedside echocardiography provides noninvasive, immediate, and low-cost monitoring of hemodynamic parameters such as cardiac output, filling pressure, structural disease, congestion status, and device functioning. Supplemented by an ultrasound of the lung and diaphragm, it is able to provide valuable information about signs suggesting a weaning failure. The aim of this article was to review the state of the art taking into account current evidence and knowledge on ICU bedside ultrasound for the evaluation of weaning from mechanical ventilation and circulatory support in cardiogenic shock.

Efficacy and safety of intermittent repeated levosimendan infusions in advanced heart failure patients: the LAICA study.

AIMS: The aim of the LAICA study was to evaluate the long-term effectiveness and safety of intermittent levosimendan infusion in patients with advanced heart failure (AdHF). METHODS AND RESULTS: This was a multicentre, randomized, double-blind, placebo-controlled clinical trial of intermittent levosimendan 0.1 µg/kg/min as a continuous 24-h intravenous infusion administered once monthly for 1 year in patients with AdHF. The primary endpoint [incidence of rehospitalization (admission to the emergency department or hospital ward for >12 h) for acute decompensated HF or clinical deterioration of the underlying HF] occurred in 23/70 (33%) of the levosimendan group (Group I) and 12/27 (44%) of the placebo group (Group II) (P = 0.286). The incidence of hospital readmissions for acute decompensated HF (Group I vs. Group II) at 1, 3, 6, and 12 months was 4.2% vs. 18.2% (P = 0.036); 12.8% vs. 33.3% (P = 0.02); 25.7% vs. 40.7% (P = 0.147); 32.8% vs. 44.4% (P = 0.28), respectively. In a secondary pre-specified time-to-event analysis no differences were observed in admission for acute decompensated HF between patients treated with levosimendan compared with placebo (hazard ratio 0.66; 95% CI, 0.32-1.32; P = 0.24). Cumulative incidence for the aggregated endpoint of acute decompensation of HF and/or death at 1 and 3 months were significatively lower in the levosimendan group than in placebo group [5.7% vs. 25.9% (P = 0.004) and 17.1% vs. 48.1% (P = 0.001), respectively], but not at 6 and 12 months [34.2% vs. 59.2% (P = 0.025); 41.4% vs. 66.6% (P = 0.022), respectively]. Survival probability was significantly higher in patients who received levosimendan compared with those who received placebo (log rank: 4.06; P = 0.044). There were no clinically relevant differences in tolerability between levosimendan and placebo and no new safety signals were observed. CONCLUSIONS: In our study, intermittent levosimendan in patients with AdHF produced a statistically non-significant reduction in the incidence of hospital readmissions for acute decompensated HF, a significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 month of treatment and a significant improvement in survival during 12 months of treatment.

Preconditioning with levosimendan reduces postoperative low cardiac output in moderate-severe systolic dysfunction patients who will undergo elective coronary artery bypass graft surgery: a cost-effective strategy.

BACKGROUND: Patients with moderate-severe systolic dysfunction undergoing coronary artery bypass graft have a higher incidence of postoperative low cardiac output. Preconditioning with levosimendan may be a useful strategy to prevent this complication. In this context, design cost-effective strategies like preconditioning with levosimendan may become necessary. METHODS: In a sequential assignment of patients with Left Ventricle Ejection Fraction less than 40%, two strategies were compared in terms of cost-effectiveness: standard care (n = 41) versus preconditioning with Levosimendan (n = 13). The adverse effects studied included: postoperative new-onset atrial fibrillation, low cardiac output, renal failure and prolonged mechanical ventilation. The costs were evaluated using deterministic and probabilistic sensitivity analysis, and Monte Carlo simulations were performed. RESULTS: Preconditioning with levosimendan in moderate to severe systolic dysfunction (Left Ventricle Ejection Fraction < 40%), was associated with a lower incidence of postoperative low cardiac output in elective coronary artery bypass graft surgery 2(15.4%) vs 25(61%) (P < 0.01) and lesser intensive care unit length of stay 2(1-4) vs 4(3-6) days (P = 0.03). Average cost on levosimendan group was 14,792€ while the average cost per patient without levosimendan was 17,007€. Patients with no complications represented 53.8% of the total in the levosimendan arm, as compared to 31.7% in the non-levosimendan arm. In all Montecarlo simulations for sensitivity analysis, use of levosimendan was less expensive and more effective. CONCLUSIONS: Preconditioning with levosimendan, is a cost-effective strategy preventing postoperative low cardiac output in patients with moderate-severe left ventricular systolic dysfunction undergoing elective coronary artery bypass graft surgery.

Diurnal variation of soluble CD40 ligand in patients with acute coronary syndrome. Soluble CD40 ligand and diurnal variation.

INTRODUCTION: We sought to investigate whether day-night variations occur in the concentration of circulating soluble CD40 ligand in patients with acute coronary syndrome, as this may have practical implications. MATERIALS AND METHODS: We assessed 70 consecutive ST-segment elevation myocardial infarction patients admitted into the Coronary Care Unit and 50 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples were drawn at 09:00 h (light phase) and 02:00 h (dark phase). Nocturnal blood samples were drawn by a trained nurse, with the help of a minute torch with a dim red light in order to avoid any direct lighting on the patient during sleep. The soluble CD40 ligand was measured using a commercially available ELISA. RESULTS: Soluble CD40 ligand levels showed no diurnal variations in control subjects. In the ST-segment elevation myocardial infarction group, however, soluble CD40 ligand concentration (pg/mL) in the light phase was significantly higher than that in the dark phase (167.3+/-63.2 vs 118.9+/-48.3 pg/mL, p<0.001). CONCLUSIONS: The study shows for the first time the existence of diurnal variations in soluble CD40 ligand levels in ST-segment elevation myocardial infarction patients, which indicates the need for standardizing the time of blood sampling for the assessment of this molecule, at least in studies involving ST-segment elevation myocardial infarction patients.

Efficient production of isomelezitose by a glucosyltransferase activity in Metschnikowia reukaufii cell extracts.

Metschnikowia reukaufii is a widespread yeast able to grow in the plants' floral nectaries, an environment of extreme conditions with sucrose concentrations exceeding 400 g l-1 , which led us into the search for enzymatic activities involved in this sugar use/transformation. New oligosaccharides were produced by transglucosylation processes employing M. reukaufii cell extracts in overload-sucrose reactions. These products were purified and structurally characterized by MS-ESI and NMR techniques. The reaction mixture included new sugars showing a great variety of glycosidic bonds including α-(1→1), α-(1→3) and α-(1→6) linkages. The main product synthesized was the trisaccharide isomelezitose, whose maximum concentration reached 81 g l-1 , the highest amount reported for any unmodified enzyme or microbial extract. In addition, 51 g l-1 of the disaccharide trehalulose was also produced. Both sugars show potential nutraceutical and prebiotic properties. Interestingly, the sugar mixture obtained in the biosynthetic reactions also contained oligosaccharides such as esculose, a rare trisaccharide with no previous NMR structure elucidation, as well as erlose, melezitose and theanderose. All the sugars produced are naturally found in honey. These compounds are of biotechnological interest due to their potential food, cosmeceutical and pharmaceutical applications.

Long-Term Radiotherapy-Induced Cardiac Complications: A Case Report.

BACKGROUND Tumor disease has improved survival due to therapeutic advances and early diagnosis. However, anti-neoplastic treatment involves generating harmful side effects in the body, both in the short-term and in the long-term. One of the most important side effects is cardiovascular disease after radiotherapy, which in addition to being influenced by classic cardiovascular risk factors, can be also be influenced by anti-neoplastic therapy, and represents the main cause of death after a second cancer. We present a case that synthesizes the most relevant and determining aspects of radiotherapy-induced heart disease. CASE REPORT We present the case of a 48-year-old male with a personal history of mediastinal Hodgkin lymphoma who was treated with local radiotherapy 20 years ago, and who was admitted to hospital due to dyspnea and oppressive chest pain with efforts. He was diagnosed with severe aortic stenosis, and a coronary angiography confirmed the existence of coronary disease. Two years before, he had been admitted to hospital due to syncope and a pacemaker had been implanted. This patient experienced several cardiovascular complications that could be attributed to the radiotherapy treatment received in his past. CONCLUSIONS Radiotherapy shows multiple cardiological complications, especially when applied at the thoracic level. This fact is very relevant, and this report can help determine the aspects of radiotherapy-induced heart disease affecting the mortality and morbidity of these patients.

Prognostic value of admission myeloperoxidase levels in patients with ST-segment elevation myocardial infarction and cardiogenic shock.

Inflammation plays a critical role in acute myocardial infarction. One inflammatory marker is myeloperoxidase (MPO). Its role as a predictor of in-hospital death in patients with ST-segment elevation myocardial infarction (STEMI) presenting with cardiogenic shock (CS) is unclear. Therefore, the aim of this study was to investigate the role of MPO as a predictor of in-hospital death in patients with STEMIs presenting with CS and treated with primary percutaneous coronary intervention. In 38 consecutive patients with CS complicating STEMIs who were treated with primary percutaneous coronary intervention, serum MPO levels were measured at coronary care unit admission using a commercially available enzyme-linked immunosorbent assay. The primary study end point was in-hospital cardiac death. Among the 38 patients included in the study, 20 died during their coronary care unit stays, whereas 18 survived. Compared with patients who survived, patients who died showed, at coronary care unit admission, higher serum MPO levels (81 +/- 28 vs 56 +/- 23 ng/ml, p <0.006). After controlling for different baseline clinical, laboratory, and angiographic variables, baseline serum MPO level was an independent predictor of in-hospital mortality on multivariate analysis (odds ratio 3.9, 95% confidence interval 1.8 to 7.5, p <0.001). In conclusion, admission MPO concentration is an independent predictor of in-hospital mortality in patients with STEMIs presenting with CS.

Relation of ischemia-modified albumin levels and left ventricular systolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Ischemia-modified albumin (IMA) has been shown to be elevated in patients after percutaneous coronary intervention (PCI). Our goal was to investigate the association between IMA levels and left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI and who developed heart failure during their Coronary Care Unit (CCU) stay. METHODS: We assessed 75 patients with a first STEMI. Presence of heart failure was assessed during CCU admission, and patients were subdivided into 2 groups: group A (n=45) comprised patients in Killip class I, and group B (n=30) Killip classes>I. Serum IMA concentration was measured within the first 15 min post-PCI. The IMA measured was performed using an indirect method based in the Albumin Cobalt Binding (ACB) colorimetric assay. The ideal cutoff value of IMA was calculated by the receiver operating characteristic (ROC) curve analysis. RESULTS: Serum IMA concentrations were significantly higher in group B than in group A (0.37+/-0.09 vs 0.30+/-0.06 (A.U.); p<0.0001). The sensitivity and specificity of IMA for heart failure were 93.3% and 37.7%, respectively, at 0.31 A.U. Multivariable adjustment IMA showed a significant inverse correlation with left ventricular ejection function (r=-0.32; p=0.004). On multivariable analysis both IMA (OR=2.1, 95%CI: 1.2 to 3.9, p<0.001) and left ventricular ejection function (OR=1.7, 95%CI: 1.1 to 2.1, p<0.01) correlated with the occurrence of heart failure. CONCLUSION: In patients with STEMI undergoing PCI, serum IMA concentrations are significantly related to LVEF and represent an early marker of left ventricular dysfunction.

Soluble CD40 ligand:interleukin-10 ratio predicts in-hospital adverse events in patients with ST-segment elevation myocardial infarction.

INTRODUCTION: The balance between pro-inflammatory and anti-inflammatory molecules is likely to modulate the processes that lead to atherogenesis and rapid coronary artery disease progression. We sought to compare the positive predictive values of serum soluble CD40 ligand (sCD40L)/interleukin-10 (IL-10) ratio, versus individual sCD40L, and IL-10 measurements regarding in-hospital events in patients admitted into the hospital with ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 96 patients with STEMI. sCD40L and IL-10 were measured at hospital admission in every patient. The composite of in-hospital death and heart failure represented the study end-point. Heart failure was defined as Killip class>1. Multivariable logistic regression analysis was performed to identify independent variables related to in-hospital events. RESULTS: Thirty two patients (33%) achieved the study end-point and 64 (67%) had no adverse events during hospital admission. IL-10 levels (pg/ml) were lower (28.2+/-9.8 versus 33.24+/-11.3, p=0.03) and sCD40L levels (pg/ml) higher (156.8+/-54.2 versus 135.4+/-38.70, p=0.02) in patients with events compared to those without events. Significantly higher odd ratios were found for sCD40L/IL-10 ratio (OR=2.10, 95% CI: 1.90 to 2.80, p=0.01) compared to individual sCD40L (OR=1.40, 95% CI: 0.90 to 2.20, p=0.08) and IL-10 (OR=0.70, 95% CI: 0.50 to 0.93, p=0.02) measurements. CONCLUSION: Our study showed that serum ratio of sCD40L/IL-10 is a better independent predictor of in-hospital adverse events than individual sCD40L and IL-10 measurements in patients with STEMI.

Relation of nocturnal melatonin levels to serum matrix metalloproteinase-9 concentrations in patients with myocardial infarction.

INTRODUCTION: The aims of the present study were to characterize the day/night variation of matrix metalloproteinase (MMP)-9 in patients who have developed ST-segment elevation myocardial infarction (STEMI), in response to light/dark differences in circulating melatonin and to assess whether melatonin, a day/night variation regulator, modulates the nocturnal inflammatory changes in patients who have STEMI. METHODS: The study included 75 patients diagnosed with STEMI and 75 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples for measurement of MMP-9 and melatonin were collected at 09:00 a.m. (light period) and 02:00 a.m. (dark period). RESULTS: In patients with STEMI, melatonin concentrations maintained a light/dark variation but the difference between nocturnal and diurnal levels was smaller than that in controls (p<0.001). In contrast to melatonin, serum MMP-9 concentrations showed no day/night variation in control subjects. MMP-9 concentrations were significantly higher in patients with STEMI than in control subjects. In the STEMI subjects, MMP-9 serum concentrations in the light period were significantly higher than those during the dark phase (291.1+/-59.5 vs. 261.8+/-57.8 ng/ml, p<0.01). Furthermore in the control subjects there was no correlation between MMP-9 and melatonin levels, while in the STEMI group there was a significant correlation between these parameters (Pearson's r=0.40, p<0.0004). CONCLUSIONS: Our results suggest that the light/dark variations in endogenous MMP-9 production in patients who have STEMI might be associated, at least in part, to the day/night variation of melatonin.

A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale.

BACKGROUND: Experimental studies have documented the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion. Melatonin confers cardioprotection against ischemia-reperfusion injury most likely through its direct free radical scavenging activities and its indirect actions in stimulating antioxidant enzymes. These actions of melatonin permit it to reduce molecular damage and limit infarct size in experimental models of transient ischemia and subsequent reperfusion. STUDY DESIGN: The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial is an unicenter, prospective, randomized, double-blind, placebo-controlled, phase 2 study of the intravenous administration of melatonin. The primary efficacy end point of this study is to determine whether melatonin treatment reduces infarct size determined by the cumulative release of alpha-hydroxybutyrate dehydrogenase (area under the curve: 0 to 72 h). Other secondary end points will be the clinical events occurring within the first 90 days: death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings, stroke, need for revascularization, recurrent ischemia, re-infarctions and rehospitalization. IMPLICATIONS: The MARIA trial tests a novel pharmacologic agent, melatonin, in patients with acute myocardial infarction and the hypothesis that it will confer cardioprotection against ischemia-reperfusion injury. If successful, the finding would support the use of melatonin in therapy of ischemic-reperfusion injury of the heart.

Bayes Syndrome and Imaging Techniques.

BACKGROUND: Interatrial block (IAB) is due to disruption in the Bachmann region (BR). According to whether interatrial electrical conduction is delayed or completely blocked through the BR, it can be classified as IAB of first, second or third degree. On the surface electrocardiogram, a P wave ≥ 120 ms (partial IAB) is observed or associated to the prolongation of the P wave with a biphasic (positive / negative) morphology in the inferior leads (advanced IAB). Bayes syndrome is defined as an advanced IAB associated with atrial arrhythmia, more specifically atrial fibrillation. Objective and Conclusion: The purpose of this review is to describe the latest evidence about an entity considered an anatomical and electrical substrate with its own name, which may be a predictor of supraventricular arrhythmia and cardioembolic cerebrovascular accidents, as well as the role of new imaging techniques, such as echocardiographic strain and cardiac magnetic resonance imaging, in characterizing atrial alterations associated with this syndrome and generally in the study of anatomy and atrial function.