Natriuretic Peptide Release Research Articles

Hypoxia stimulates the release of Brain Natriuretic Peptide (BNP) from RPE cells

AbstractPurpose The natriuretic peptide system (A‐, B‐ and C‐type) has a powerful effect on systemic blood circulation (natriuresis, diuresis ans plasma shift) causing haemoconcentration causing increased oxygen carrying capapcity of blood. A high concentration of a member of the natriuretic peptide family has been found from the vitreous of patients suffering of proliferative diabetic retinopathy (PDR). The stimulus to which the natriuretic peptide system responded in PDR, however, has remained unknown. We tested the hypothesis that hypoxic conditions will increase the release of BNP (B‐type of natriuretic peptides) from human retinal pigment epithelium (RPE) cell cultureMethods Human retinal pigment epithelium cells (ARPE‐19) were exposed to hypoxia for 2h, 4h, 6h, 8h and 24h. The amount of BNP and VEGF (positive control) were measured at different time points in culture media using EIA. Hypoxia‐Inducible Factor (HIF), a protein, which is the master switch in regulating all the responses to hypoxia downstream, was measured using Western blotting.Results At 24h, the amount of BNP in culture media was significantly higher in hypoxic than in normoxic conditions. Also, the concentration of both VEGF and HIF were significantly higher in hypoxia.Conclusion Hypoxia increases the release of BNP from RPE cells and the response is mediated by HIF.The present results characterize for the first time a stimulus for the natriuretic peptide system in human retina and explain previous clinical findings. Thus, the measurement of natriuretic peptides in the vitreous may guide the treatment of the intraocular diseases in which the retina is suffering from hypoxia. Future perspectives: Natriuretic peptides regulate oxygen transport in all tissues?

IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytesin vitroand its plasma levels correlate with B-type natriuretic peptide innon-overloadedacute heart failure patients

An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic, and profibrotic activities. B-type natriuretic peptide is a cardiac hormone produced in response to cardiac filling to regulate cardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients. We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line to express the B-type natriuretic peptide gene, synthesize the relative protein through a PI3K-AKT-dependent transduction, and induce a cell secretory phenotype with B-type natriuretic peptide release. A correlation between IL-18 and B-type natriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patients with diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levels than patients without. IL-18 plasma levels were correlated with C-reactive protein plasma levels. This study provides the first evidence of the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status.

Oxytocin Ameliorates the Immediate Myocardial Injury in Rat Heart Transplant Through Downregulation of Neutrophil-Dependent Myocardial Apoptosis

BackgroundCardiac oxytocin (OT) is structurally identical to that found in the hypothalamus, indicating that this active form of OT is derived from the same gene. The abundance of OT and its receptors in atrial myocytes suggests that, directly and/or via the release of the cardiac hormone atrial natriuretic peptide, this hormone regulates the force of cardiac contractions. Previous studies have demonstrated a role of OT in myocardial inflammatory responses. We sought to study protective myocardial and anti-inflammatory effects of OT in the immediate post-transplant period. MethodsWe grouped adult male Albino rats into sham, control, and OT-treated groups. Control and treated groups underwent heterotopic cervical heart transplantation. Myocardial injury was assessed by measuring plasma cardiac troponin I, and myocardial proinflammatory cytokines as well as by performing histopathologic assessments injury score, and of apoptotic degree. Myocardial myeloperoxidase, neutrophil infiltration, neutrophil chemotactic mediators as well as formation of reactive oxygen and reactive nitrogen species were measured in the myocardium at 3 hours after reperfusion to assess neutrophil-dependent myocardial injury. ResultsOT downregulates neutrophil chemotactic molecules — KC/CXCL1 and MIP-2/CXCL2. The decrement in myocardial PMN infiltration was associated with reduced reactive oxygen and reactive nitrogen species formation in the myocardium at 3 hours after reperfusion following global ischemia. OT reduced postmyocardial ischemia/reperfusion apoptotic processed. ConclusionOT ameliorated immediate myocardial injury in heart grafts, through downregulation of the inflammatory response, of reactive oxygen species, and of neutrophil dependent apoptosis.

Venous congestion and renal function in heart failure … it's complicated

Venous congestion and renal function in heart failure … it's complicated

Coronary Microvascular Dysfunction and Diastolic Load Correlate With Cardiac Troponin T Release Measured by a Highly Sensitive Assay in Patients With Nonischemic Heart Failure

This study investigated factors associated with cardiac troponin T (cTnT) release from failing myocardium. Persistent and modest elevation of serum cTnT is frequently observed in heart failure (HF) patients free of coronary artery disease, although the mechanisms underlying this finding remain unclear. We evaluated serum cTnT levels in the aortic root (Ao) and coronary sinus (CS) using a highly sensitive assay in 90nonischemic HF patients and 47 non-HF patients. Transcardiac cTnT and plasma B-type natriuretic peptide (BNP) release were described as the differences between CS and Ao cTnT levels [ΔcTnT (CS-Ao)] and BNP levels [ΔBNP (CS-Ao)], respectively. Coronary flow reserve (CFR) was measured in 68 HF patients using an intracoronary Doppler guidewire. ΔcTnT (CS-Ao) levels were available in 76 HF patients and 28 non-HF patients (84% vs. 60%; p= 0.001), and higher in HF patients than non-HF patients (p< 0.001). Among HF patients, log[ΔcTnT (CS-Ao)] correlated with log[ΔBNP (CS-Ao)] (r= 0.368, p= 0.001), pulmonary capillary wedge pressure (r= 0.253, p= 0.03) and left ventricular end-diastolic pressure (LVEDP) (r= 0.321, p= 0.005). Multivariate regression analysis identified LVEDP as an independent parameter that correlated with ΔcTnT (CS-Ao). ΔcTnT (CS-Ao) levels were available in 58 HF patients who were evaluated for CFR. Coronary microvascular dysfunction, diagnosed by CFR<2.0, was observed in 18 HF patients. ΔcTnT (CS-Ao) was higher in patients with coronary microvascular dysfunction (4.8 [2.0 to 8.1] ng/l) than those without (2.0 [1.2 to 4.6] ng/l; p= 0.04). cTnT release from failing myocardium correlated with diastolic load and coronary microvascular dysfunction in nonischemic HF patients.

Isoproterenol instigates cardiomyocyte apoptosis and heart failure via AMPK inactivation-mediated endoplasmic reticulum stress

A prolonged or excessive adrenergic activation leads to myocyte loss and heart dysfunction; however, how it contributes to heart failure remains poorly defined. Here we show that isoproterenol (ISO) induced aberrant endoplasmic reticulum (ER) stress and apoptotic cell death, which was inhibited by activating the AMP-activated protein kinase (AMPK) in vitro and in vivo. Persistent ISO stimulation suppressed the AMPK phosphorylation and function, resulting in enhanced ER stress and the subsequent cell apoptosis in cardiomyocytes in vitro and in vivo. AMPK activation decreased the aberrant ER stress, apoptosis, and brain natriuretic peptide (BNP) release in ISO-treated cardiomyocytes, which was blocked by AMPK inhibitor Compound C. Importantly, increased ER stress and apoptosis were observed in ISO-treated cardiomyocytes isolated from AMPKα2(-/-) mice. Inhibition of ER stress attenuated the apoptosis but failed to reverse AMPK inhibition in ISO-treated cardiomyocytes. Moreover, metformin administration activated AMPK and reduced both ER stress and apoptosis in ISO-induced rat heart failure in vivo. We conclude that ISO, via AMPK inactivation, causes aberrant ER stress, cardiomyocyte injury, BNP release, apoptosis, and hence heart failure in vivo, all of which are inhibited by AMPK activation.

Dissociation Between Severity of Takotsubo Cardiomyopathy and Presentation With Shock or Hypotension

Takotsubo cardiomyopathy (TTC) is increasingly well-recognized as a cause of chest-pain syndromes, especially in aging females. The most common complications of TTC occur in the first 24 hours post onset of symptoms and include shock and/or arrhythmias. We tested the hypothesis that the severity of early hypotension in TTC reflects the extent of myocardial involvement and dysfunction. In 80 consecutive TTC patients, correlates of blood pressure on the day of admission were sought via univariate followed by multivariate analysis. Mean systolic blood pressure (SBP) on day 1 was 120 ± 24 (SD) mm Hg. During the first 3 days of admission, 39% of patients had SBP <90 mm Hg, and 9% died and/or required intra-aortic balloon pump insertion. The extent of release of N-terminal pro-brain natriuretic peptide, with its potential correlate of associated vasodilator activity, varied inversely with pulmonary-artery saturation, a measure of cardiac output. However, there was no significant relationship between normetanephrine release and SBP. On multivariate analyses there was no significant relationship between SBP and (1) wall-motion score index (as an index of left-ventricular systolic dysfunction) or (2) T2 enhancement on cardiac magnetic resonance imaging and peak N-terminal pro-brain natriuretic peptide (as indices of myocardial inflammation). Although severe hypotension and shock occur commonly during acute stages of TTC, these complications are multifactorial in origin, probably representing a combination of impaired inotropic state and vasodilatation. Importantly, initial hypotension does not imply severe left ventricular inflammation or systolic dysfunction.

Reversible Myocardial Dysfunction and Clinical Outcome in Scuba Divers With Immersion Pulmonary Edema

Immersion pulmonary edema in scuba divers is a rare disorder that tends to recur and can be potentially fatal, even in the absence of underlying cardiac disease. Anecdotal cases of reversible myocardial dysfunction have been described in this setting, but little is known of its pathogenesis. The purpose of the present study was to determine the clinical outcomes and the determinants associated with this condition. The data from 54 consecutive divers admitted for acute immersion pulmonary edema during a 5.5-year period were retrospectively studied. A diagnosis of myocardial dysfunction was established by the presence of elevated cardiac troponin T levels, coupled with electrocardiographic changes and/or wall motion abnormalities on the echocardiogram. The demographic, clinical, biologic, and diving characteristics were tested as potential predictors of this disorder. All the patients had complete resolution of symptoms within 72 hours, but 3 required intensive ventilation or hemodynamic support at admission. Reversible myocardial dysfunction was observed in 28% and was associated more with age >50 years (odds ratio [OR] 5.5, 95% confidence interval [CI] 1.5 to 21, p= 0.013), hypertension (OR 8.2, 95% CI 2.1 to 32, p= 0.002), diabetes (OR 22.1, 95% CI 1.1 to 458; p= 0.002), and release of natriuretic peptides (OR 9.1, 95% CI 2.4 to 35, p= 0.001). Follow-up investigations at 1 month were obtained for 49 patients and revealed a significant number of patients with occult hypertension. In conclusion, reversible myocardial dysfunction is not uncommon in divers with immersion pulmonary edema. The short-term overall prognosis is not adversely altered, but severe heart failure with a fatal outcome is unpredictable. Close monitoring of older divers with latent cardiovascular risk factors is warranted.

Release of ANP and Fat Oxidation in Overweight Persons during Aerobic Exercise in Water

Exercise in water compared to land-based exercise (LE) results in a higher release of natriuretic peptides, which are involved in the regulation of exercise-induced adipose tissue lipolysis. The present study was performed to compare the release of atrial natriuretic peptide (ANP) and free fatty acids (FFA) during prolonged aerobic water-based exercise (WE) with the release after an identical LE. 14 untrained overweight subjects performed 2 steady state workload tests on the same ergometer in water and on land. Before and after exercise, venous blood samples were collected for measuring ANP, FFA, epinephrine, norepinephrine, insulin and glucose. The respiratory exchange ratio (RER) was determined for fat oxidation.The exercises resulted in a significant increase in ANP in LE (61%) and in WE (177%), and FFA increased about 3-fold in LE and WE with no significant difference between the groups. Epinephrine increased, while insulin decreased similarly in both groups. The RER values decreased during the exercises, but there was no significant difference between LE and WE. In conclusion, the higher ANP concentrations in WE had no additional effect on lipid mobilization, FFA release and fat oxidation. Moderate-intensity exercises in water offer no benefit regarding adipose tissue lipolysis in comparison to LE.

La presión arterial ambulatoria nocturna se asocia al remodelado auricular y la activación neurohormonal en pacientes con fibrilación auricular idiopática

Introduction and objectivesHypertension is a risk factor for atrial fibrillation. Activation of the renin-angiotensin-system seems to be involved in atrial enlargement, with release of atrial and brain natriuretic peptides. The aim of this study was to evaluate the relationship between ambulatory blood pressure and levels of natriuretic peptides, with left atrial size in normotensives with idiopathic atrial fibrillation. MethodsThis was a cross-sectional study in patients with idiopathic atrial fibrillation. The following measurements were recorded during the course of the study: office and 24-h ambulatory blood pressure, atrial and brain natriuretic peptides, plasma renin, aldosterone, and angiotensin-converting enzyme. ResultsForty-eight patients (mean age 55 [10] years; 70.6% male) were included in the study. Mean office sitting blood pressure values were 132.49 (14.9)/80.96 (9.2) mmHg. Mean 24-h ambulatory systolic and diastolic blood pressure values were 121.10 (8.3)/72.11 (6.8) mmHg (daytime, 126.8 [9.7]/77.58 [7.9] mmHg; nighttime, 114.56 [11.6]/68.6 [8.8] mmHg). A clear trend towards increased left atrial size with higher ambulatory blood pressure values was noted, which was statistically significant for nighttime values (r=0,34; P=.020 for systolic and r=0,51; P=.0001 for diastolic). A significant correlation between atrial natriuretic peptide and nighttime systolic (r=0,297; P=.047) and diastolic (r=0,312; P=.037) blood pressure was observed. Significant correlations were also observed between left atrial size and atrial natriuretic peptide levels (r=0,577; P<.0001) and brain natriuretic peptide levels (r=0,379; P=.012). ConclusionsNighttime blood pressure is associated with left atrial size and the release of natriuretic peptides in normotensive patients with idiopathic atrial fibrillation.Full English text available from:www.revespcardiol.org/en

Nighttime Ambulatory Blood Pressure is Associated With Atrial Remodelling and Neurohormonal Activation in Patients With Idiopathic Atrial Fibrillation

Introduction and objectivesHypertension is a risk factor for atrial fibrillation. Activation of the renin-angiotensin-system seems to be involved in atrial enlargement, with release of atrial and brain natriuretic peptides. The aim of this study was to evaluate the relationship between ambulatory blood pressure and levels of natriuretic peptides, with left atrial size in normotensives with idiopathic atrial fibrillation. MethodsThis was a cross-sectional study in patients with idiopathic atrial fibrillation. The following measurements were recorded during the course of the study: office and 24-h ambulatory blood pressure, atrial and brain natriuretic peptides, plasma renin, aldosterone, and angiotensin–converting enzyme. ResultsForty-eight patients (mean age 55 [10] years; 70.6% male) were included in the study. Mean office sitting blood pressure values were 132.49 (14.9)/80.96 (9.2) mmHg. Mean 24-h ambulatory systolic and diastolic blood pressure values were 121.10 (8.3)/72.11 (6.8) mmHg (daytime, 126.8 [9.7]/77.58 [7.9] mmHg; nighttime, 114.56 [11.6]/68.6 [8.8] mmHg). A clear trend towards increased left atrial size with higher ambulatory blood pressure values was noted, which was statistically significant for nighttime values (r=0.34; P=.020 for systolic and r=0.51; p=.0001 for diastolic). A significant correlation between atrial natriuretic peptide and nighttime systolic (r=0.297; P=.047) and diastolic (r=0.312; P=.037) blood pressure was observed. Significant correlations were also observed between left atrial size and atrial natriuretic peptide levels (r=0.577; p<.0001) and brain natriuretic peptide levels (r=0.379; P=.012). ConclusionsNighttime blood pressure is associated with left atrial size and the release of natriuretic peptides in normotensive patients with idiopathic atrial fibrillation.

In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.

This study reports on the release of a novel natriuretic peptide, CD-NP, from an in situ polymer precipitation delivery system. Following extensive screening of in-vitro release profiles, an in-vivo evaluation of the efficacy of the delivery system was carried out in Wistar rats. Gel injection was performed subcutaneously on the back of the rats. A secondary messenger, cyclic Guanosine 3′5′ Monophosphate (cGMP), was tested for verification of CD-NP bioactivity, in addition to direct measurements of CD-NP levels in plasma and urine using a radio-immuno assay. Plasma evaluation showed an elevated level of CD-NP over 3 weeks' duration. Unexpectedly, plasma cGMP level followed a decreasing trend over the same duration despite high CD-NP level. Loss of drug bioactivity was ruled out as a high level of CD-NP and cGMP excretion was observed in the treatment group as compared to baseline readings. This unexpected low-plasma cGMP levels and high-urinary cGMP excretion suggest that there might be other compensatory responses to regulation of the CDNP bioactivity as a result of the high drug dosing. The results stress the importance of assessing the overall bioactivity of released drug (in-vivo) concurrently in addition to measuring its concentrations, to determine the correct release profile.

Release of NT-pro brain natriuretic peptide in children before and after adenotonsillectomy

ObjectivesTo measure serum B-type natriuretic peptide, especially N-terminal segment of its prohormone (NT-proBNP) and pulmonary arterial pressure levels and to determine whether NT-proBNP concentrations correlate with pulmonary arterial pressure levels in children before and after adenotonsillectomy. MethodsTwenty children with adenoid and tonsil hypertrophy and 20 healthy subjects were included in the study. Transthoracic echocardiography was performed in all patients to assess pulmonary artery systolic and diastolic pressure with cardiac dysfunction. The NT-proBNP was analyzed for correlation with pulmonary artery pressure. ResultsOur results showed that prohormone serum concentrations and pulmonary arterial pressures were significantly higher in the study group than in the control group at the preoperative evaluation. A significant decrease was detected among patients after surgery (p<0.05). There was no significant difference between the study and control groups for prohormone serum concentration and pulmonary arterial pressure at the postoperative evaluation (p>0.05). ConclusionWe found increased serum prohormone levels and height pulmonary artery pressures in the children with adenoid and tonsil hypertrophy when comparing with healthy subjects. Our study supported that increased serum prohormone levels and pulmonary artery pressures as a result of adenoid and tonsil hypertrophy are reversible. Pediatric cardiologs and otolaryngologs should keep in mind an increased pulmonary artery pressure during management of children with adenoid and tonsil hypertrophy. Furthermore, Doppler echocardiography may be useful in the monitoring of pulmonary arterial pressure and in the follow-up of surgical outcome of children with adenoid and tonsil hypertrophy.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Does hypoxemia have an impact on the cardiac release and circulating concentrations of natriuretic peptides in humans in vivo?

A large number of experimental studies have suggested that hypoxia may be a potent stimulus for the myocardial synthesis and release of A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) [1]. However, these studies have evaluated either the effect of hypoxia on ANP and/or BNP production in isolated cardiomyocytes [2,3], isolated perfused hearts [4,5], or animals [5,6], or on the circulating concentrations of ANP, BNP, and/or N-terminal pro-BNP (NT-proBNP) but not on the cardiac release of these peptides in humans [7–9].

Changes in brain natriuretic peptide are correlated with changes in global end-diastolic volume index.

It is believed that the stretch of cardiomyocytes is the most important stimulus of brain natriuretic peptide (BNP) release; however, its correlation with volume status represented by global end diastolic volume index (GEDVI) is less well established. The study aimed to investigate the correlation between the changes in BNP and the changes in GEDVI measured with transpulmonary thermodilution technique. Critically ill patients requiring hemodynamic monitoring (PiCCO system) in a tertiary 18-bed intensive care unit were prospectively enrolled. Hemodynamic variables were measured simultaneously with blood sampling for BNP concentration. Correlations between changes in BNP and changes in GEDVI were tested using pairwise correlation analysis. A total of 46 patients were included in the study. BNP level (median 4,602 pg/mL; IQR 1,988 to 12,439 pg/mL) was markedly elevated in the study population, but was not correlated with GEDVI (rho=-0.09, P=0.56). The changes in BNP (ΔBNP) showed significant correlation with changes in GEDVI (ΔGEDVI) (Figure 2; rho=0.52, P<0.01). Variables including Age (r=0.43, P=0.002), serum creatinine (r=0.36, P=0.012) and cardiac index (CI) (r=-0.35, P=0.016) were also significantly correlated with logBNP. Other variables such as APACHE II score, central venous pressure (CVP), heart rate (HR), intrathoracic blood volume (ITBVI), extravascular lung water (EVLWI) and systemic vascular resistance index (SVRI) were not significantly correlated with logBNP. Changes in BNP concentrations are correlated with changes in GEDVI and serial measurements of BNP concentrations may be a useful tool for monitoring volume status.

B-Type Natriuretic Peptide Modulates Ghrelin, Hunger, and Satiety in Healthy Men

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart–gut–brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

Hypoxia stimulates the synthesis and release of Brain Natriuretic Peptide (BNP) in RPE cells

AbstractPurpose Blood flow and oxygen availability of the retina are modulated by locally produced peptides that also can change the function of neurons. The natriuretic peptide system has been isolated and characterized in human retina and these peptides localize in retinal pigment epithelium (RPE) cells. A high concentration of natriuretic peptides has been previously measured from the vitreous of patients suffering of proliferative diabetic retinopathy (PDR). However, the stimulus to which the natriuretic peptide system responds in PDR has remained unknown. We hypothesized that hypoxic conditions will increase the synthesis and release of Brain Natriutretic peptide (BNP) from human RPE cell culture.Methods Human RPE cell were exposed to hypoxia for several hours. Samples were collected at time intervals and analyzed for BNP peptide and for BNP mRNA. A simultaneous measurement of VEGF served as a positive control.Results In hypoxic conditions RPE cells secreted statistically significant amounts of BNP.Conclusion These findings characterize for the first time a stimulus for the natriuretic peptide system in the retina and explain previous clinical findings. Thus, the measurement of natriuretic peptides from the vitreous may guide the treatment of the intraocular diseases in which the retina is suffering from hypoxia.

Systems Biology and Biomechanical Model of Heart Failure

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.

New-onset migraine with aura after transcatheter closure of atrial septal defect

Transcatheter closure of atrial septal defect (ASD) is associated with a high success rate and become an accepted alternative to surgical treatment. We describe here a case of a 35-year-old woman who presented with migraine attacks with aura after transcatheter closure of ASD with an Amplatzer septal occluder device. We postulate that any of the following may have been responsible for her condition: platelet activation on the surface of the device, nickel allergy, or the release of the atrial natriuretic peptide associated with the stretch of the atrial septum caused by the device. This case demonstrates that de novo migraine can occur after transcatheter closure of ASD and should be recognized as a potential complication.