Lateral Parabrachial Afferent Areas and Serotonin Mechanisms Activated by Volume Expansion

Recent evidence has shown that the serotonergic mechanism of the lateral parabrachial nucleus (LPBN) participates in the regulation of renal and hormonal responses to isotonic blood volume expansion (BVE). We investigated the BVE-induced Fos activation along forebrain and hindbrain nuclei and particularly within the serotonergic clusters of the raphe system that directly project to the LPBN. We also examined whether there are changes in the concentration of serotonin (5HT) within the raphe nucleus in response to the same stimulus. With this purpose, we analyzed the cells doubly labeled for Fos and Fluorogold (FG) following BVE (NaCl 0.15 M, 2 ml/100 g b.w., 1 min) 7 days after FG injection into the LPBN. Compared with the control group, blood volume-expanded rats showed a significant greater number of Fos-FG double-labeled cells along the nucleus of the solitary tract, locus coeruleus, hypothalamic paraventricular nucleus, central extended amygdala complex, and dorsal raphe nucleus (DRN) cells. Our study also showed an increase in the number of serotonergic DRN neurons activated in response to isotonic BVE. We also observed decreased levels of 5HT and its metabolite 5-hydroxyindoleacetic acid (measured by high-pressure liquid chromatography) within the raphe nucleus 15 min after BVE. Given our previous evidence on the role of the serotonergic system in the LPBN after BVE, the present morphofunctional findings suggest the existence of a key pathway (DRN-LPBN) that may control BVE response through the modulation of 5HT release. (c) 2008 Wiley-Liss, Inc.

Adrenalectomy enhances endotoxemia-induced hypophagia: higher activation of corticotrophin-releasing-factor and proopiomelanocortin hypothalamic neurons

Inflammatory and infectious processes evoke neuroendocrine and behavioral changes known as acute-phase response that includes activation of the hypothalamo-pituitary-adrenal (HPA) axis and reduction of food intake. Besides its action as the most important ACTH secretagogue, corticotrophin-releasing factor (CRF), synthesized in the paraventricular nucleus (PVN), is also involved in the control of food intake. Alpha-melanocyte stimulating hormone (alpha-MSH) in the arcuate nucleus also plays a role in the energy homeostasis, possessing anorexigenic effects. To investigate the participation of neuropeptides involved in the regulation of food intake during endotoxemia, we administrated lipopolysaccharide (LPS) in sham-operated and adrenalectomized (ADX) male Wistar rats to evaluate food intake, hormone responses and Fos-CRF and Fos-alpha-MSH immunoreactivity in the PVN and arcuate nucleus, as well as CRF and POW mRNA expression in these hypothalamic nuclei. In sham-operated rats, treatment with LPS (100 mu g/kg) showed lower food intake, higher plasma ACTH and corticosterone levels, as well as an increase in Fos-CRF double labeled neurons and CRF mRNA expression in the PVN, with no changes in Fos-alpha-MSH immunoreactivity and POW mRNA expression in the arcuate nucleus, compared to saline treated rats. After LPS treatment, ADX rats showed further increase in plasma ACTH levels, marked decrease of food intake, higher Fos-CRF immunoreactive neurons in the PVN and CRF mRNA expression, as well as an increase in Fos-alpha-MSH immunoreactivity and POW mRNA expression in the arcuate nucleus, compared to sham-operated rats treated with LPS. In conclusion, the present data indicate that the marked hypophagia during endotoxemia following ADX is associated with an increased activation of CRF and POW neurons in the hypothalamus and an increased mRNA expression of these neuropeptides. (C) 2008 Elsevier Inc. All rights reserved.

LONGITUDINAL REFERENCE VALUES FOR DUCTUS VENOSUS DOPPLER IN LOW-RISK PREGNANCIES

The aim of this study was to establish normal ranges of blood flow velocities and indices in the fetal ductus venosus (DV) during the second half of normal pregnancy. A Doppler study of 60 healthy pregnant women without fetal pathologies was performed during the second half of pregnancy. The peak systolic velocity (PSV), peak diastolic velocity (PDV), maximum velocity during atrial contraction (VAC), peak systolic velocity/maximum velocity during atrial contraction (S/A ratio), pulsatility index for the vein (PIV), preload index (PLI) and velocity index for the vein (VIV) were calculated from the DV at 4-week intervals. A significant increase in PSV, PDV and VAC was observed from the 20-23(6/7) to the 28-31(6/7) weeks, with stabilization of values until the end of the pregnancy. On the other hand, the study showed a significant decrease for the S/A ratio, PIV, PLI and VIV from the 20-23(6/7) to the 28-31(6/7) weeks and remaining stable from then until term. (E-mail:dralemar@uol.com.br) (C) 2010 World Federation for Ultrasound in Medicine & Biology.

Perinatal outcome of fetal atrioventricular block - One-hundred-sixteen cases from a single institution

Background-Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results-Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n = 40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate <= 120 bpm, and a ventricular rate <= 55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death (P < 0.001). Conclusions-This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of >90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents.

Percutaneous Transatrial Access to the Pericardial Space for Epicardial Mapping and Ablation

Background-Puncture of the atrial appendage may provide access to the pericardial space. The aim of this study was to evaluate the feasibility of epicardial mapping and ablation through an endocardial transatrial access in a swine model. Methods and Results-An 8-F Mullins sheath was used to perforate the right (n=16) or left (n=1) atrial appendage in 17 pigs (median weight, 27.5 kg; first and third quartiles [Q1, Q3], 25.2, 30.0 kg). A 7-F ablation catheter was introduced into the pericardial space to perform epicardial mapping and deliver radiofrequency pulses on the atria. The pericardial space was entered in all 17 animals. In 15 (88%) animals, there was no hemodynamic instability (mean blood pressure monitoring, initial median, 80 mm Hg; Q1, Q3, 70, 86 mm Hg; final median, 88 mm Hg; Q1, Q3, 80, 96 mm Hg; P=0.426). In these 15, a mild hemorrhagic pericardial effusion was identified and aspirated (median, 20 mL; Q1, Q3, 15, 30 mL) during the procedure, and postmortem gross analysis revealed that the atrial perforation was closed in these animals. In 2 (12%) of the 17 animals, there was major pericardial bleeding with hemodynamic collapse. On gross examination, it was found that pericardial space was accessed through right ventricular perforation in 1 animal and the tricuspid annulus in the other. After the initial study, we used an occlusion device in 3 other animals to attempt to seal the puncture (2 at the right atrial appendage and 1 at the right ventricle). These 3 animals had no significant pericardial bleeding. Conclusions-Transatrial endovascular right atrial appendage puncture may provide a potential alternative route for pericardial access. Further studies are needed to evaluate its safety with longer and more-complex procedures before being applied in clinical settings. (Circ Arrhythm Electrophysiol. 2011;4:331-336.)

Holt-Oram syndrome: novel TBX5 mutation and associated anomalous right coronary artery

The Holt-Oram syndrome was confirmed in an asymptomatic 36-year-old man by a novel TBX5-gene mutation (exon 8 acceptor splicing site, c.663-1G greater than A). Computed tomography showed an atrial septal defect and an anomalous right coronary artery crossing between the aorta and pulmonary arteries. Surgery corrected the septal defect and the initial segment of the anomalous vessel was unroofed and enlarged. Anomalous coronary arteries were not previously described in the Holt-Oram syndrome patients and should be added to the list of possible associated cardiac defects.

Thyroid gland and cerebella lesions: New risk factors for sudden cardiac death in schizophrenia?

People with schizophrenia show a two to threefold increased risk to die prematurely than those without schizophrenia. Patients` life style, suicide, premature development of cardiovascular disease, high prevalence of metabolic syndrome and sudden cardiac death are well-known causes of the excess mortality. The exact pathophysiological cause of sudden death in schizophrenia is unknown, but it is likely that cardiac arrhythmia and respiratory abnormalities play potential role. Some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation) and lesions in specific brain regions, such as cerebella may be associated with respiratory abnormalities, suggesting that metabolic and brain dysfunction could lead to sudden cardiac death in patients with schizophrenia. However, exact knowledge regarding the association of these findings and schizophrenia is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease and cerebella progressive atrophy has been observed in patients with schizophrenia, we propose in this paper that subclinical thyroid dysfunction and cerebella volume loss could be considered as new risk factor for sudden cardiac death in schizophrenia. (C) 2010 Elsevier Ltd. All rights reserved.

Prevalence and diagnostic workup of primary aldosteronism: new knowledge and new approaches

No Abstract

Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta(1)/beta(2)-adrenoceptor knockout mice. Obligatory role of beta(1)-adrenoceptors for putative beta 4-adrenoceptor pharmacology

Some beta (1)- and beta (2)-adrenoceptor-blocking agents, such as (-)-CGP 12177, cause cardiostimulant effects at concentrations considerably higher than those that antagonise the effects of catecholamines. The cardiostimulant effects of these non-conventional partial agonists are relatively resistant to blockade by (-)-propranolol and have been proposed to be mediated through putative beta (4)-adrenoceptors or through atypical states of either beta (1)- or beta (2)-adrenoceptors. We investigated the effects of (-)-CGP 12177 on sinoatrial rate and left atrial contractile force as well as the ventricular binding of (-)-[H-3]CGP 12177 in tissues from wild-type, beta (2)-adrenoceptor knockout and beta (1)/beta (2)-adrenoceptor double knockout mice. The cardiostimulant effects of (-)-CGP 12177 were present in wildtype and beta (2)-adrenoceptor knockout mice but were absent in beta (1)/beta (2)-adrenoceptor double knockout mice. Thus, the presence of beta (1)-adrenoceptors is obligatory for the cardiostimulant effects of (-)-CGP 12177. It appears therefore that an atypical state of the beta (1)-adrenoceptor contributes to the mediation of the cardiostimulant effects induced by non-conventional partial agonists. Ventricular beta (1)- and beta (2)-adrenoceptors, labelled in wild-type with a K(D)similar to0.5 nmol/l (similar to 16 fmol/mg protein), were absent in beta (1)/beta (2)-adrenoceptor double knockout mice. However, a high density binding site (similar to 154-391 fmol/mg protein) that did not saturate completely (K(D)similar to 80-200 nM) was labelled by (-)-[H-3]CGP 12177 in the three groups of mice, being distinct from beta (1)- and beta (2)-adrenoceptors, as well as from the site mediating the agonist effects of(-)-CGP 12177.

Cardiostimulant effects of urotensin-II in human heart in vitro

The effects of the recently identified human peptide urotensin-II (hU-II) were investigated on human cardiac muscle contractility and coronary artery tone. In right atrial trabeculae from non-failing hearts, hU-II caused a concentration-dependent increase in contractile force (pEC(50)=9.5+/-0.1; E-max= 31.3+/-4.8% compared to 9.25 mM Ca2+; n = 9) with no change in contraction duration. In right ventricular trabeculae from explanted hearts, 20 nM hU-II caused a small increase in contractile force (7.8+/-1.4% compared to 9.25 mM Ca2+; n= 3/6 tissues from 2 out of 4 patients). The peptide caused arrhythmic contractions in 3/26 right atrial trabeculae from 3/9 patients in an experimental model of arrhythmia and therefore has less potential to cause arrhythmias than ET-1. hU-II (20 nM) increased tone (17.9% of the response to 90 mM KCI) in 7/7 tissues from 1 patient, with no response detected in 8/8 tissues from 2 patients. hU-II is a potent cardiac stimulant with low efficacy.

Using postoperative cardiac troponin-I (cTi) levels to detect myocardial ischaemia in patients undergoing vascular surgery

Background, Cardiac complications occur commonly in vascular surgery patients. Diagnosis of cardiac complications is difficult because of the inaccuracies associated with traditional cardiac enzyme measurements. CTi, a highly sensitive and specific marker of myocardial injury, may be able to detect cardiac complications with greater ease and accuracy. Methods. The study prospectively examined 100 consecutive patients who underwent major vascular surgery between 6/7/98 and 31/12/98 at the Royal Brisbane Hospital. Daily measurements of cTi, creatine kinase (CK), creatine kinase MB (CKMB), CKMB index, renal function and haemoglobin were taken for three postoperative days. One postoperative electrocardiograph (ECC) was taken. An extensive cardiac history was taken. Intraoperative and postoperative events were recorded. Findings. There were 100 patients, 18 patients (18%) had a cTi elevation. On the basis of classical diagnostic criteria, 15 patients (15%) suffered one or more cardiac complication (either myocardial infarction, congestive cardiac failure, unstable angina or atrial fibrillation), One patient (1%) who had a cTi elevation died. CTI elevation occurred in five patients (5%) who were not diagnosed with cardiac complications based on traditional criteria. Despite not meeting specific diagnostic criteria for cardiac complications, all patients showed signs and symptoms that could be attributed to myocardial ischaemia, Every patient who developed congestive cardiac failure or atrial fibrillation had a cTi elevation. A Chi-square analysis revealed a significant association between cTi elevation and postoperative cardiac complications. Four variables contributed small but significant amounts of unique variance to the prediction of peak cTi on linear regression analysis. These were peak CKMB index, postoperative congestive cardiac failure, postoperative chest pain and postoperative cardiac complications. Conclusions. Routine cTi monitoring of postoperative vascular patients would be an effective and inexpensive way to detect patients with cardiac complications. The relationship between postoperative cTi elevation and significant coronary artery disease remains to be shown, (C) 2001 The international Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved.

Amiodarone - waxed and waned and waxed again

Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Amiodarone is a structural analogue of thyroid hormone and some of its anti-arrhythmic properties and toxicity may be attributable to interactions with nuclear thyroid hormone receptors. The lipid solubility of amiodarone gives it an exceptionally long half-life. Oral amiodarone takes days to work in ventricular tachyarrhythmias, but iv. amiodarone has immediate effect and can be used in life threatening ventricular arrhythmias. Intravenous amiodarone administered after out-of-hospital cardiac arrest due to ventricular fibrillation improves survival to hospital admission. Many survivors of myocardial infarction (MI) die during the subsequent year, probably due to ventricular arrhythmia. Amiodarone reduces sudden death after MI and this benefit is predominantly observed in patients with preserved cardiac function. Sudden cardiac death, predominantly due to ventricular arrhythmias, is also commonly seen in patients with heart failure. The Grupo de Estudio de la Sobrevida en lsuficiencia Cardiaca en Argentina (GESICA) and Estudio Piloto Argentino de Muerte Subita y Amiodarona (EPAMSA) trials showed survival benefit of amiodarone in heart failure, whereas Congestive Heart Failure-Survival Trial of Anti-arrhythmic Therapy (CHF-STAT) did not. Subsequent meta-analysis established a survival benefit of amiodarone in heart failure. Implanted Cardioverter Defibrillators (ICDs) also give survival benefit to patients at risk of sudden death. In patients with a history of ventricular fibrillation or haemodynamically-compromising ventricular tachycardia, ICDs have been shown to be superior to anti-arrhythmic drugs, principally amiodarone. Further analysis has been undertaken to ascertain which patients are most likely to benefit from ICDs, as these are more expensive than treatment with amiodarone. Patients with severely depressed ejection fractions should be the first to be considered for ICDs. A new indication for amiodarone is atrial fibrillation or flutter. Amiodarone is effective in chronic and recent onset atrial fibrillation and orally or iv. for atrial fibrillation after heart surgery. In atrial fibrillation amiodarone is more than or equi-effective with flecainide, quinidine, racemic sotalol, propafenone and diltiazem and therefore should be considered for first line therapy. Amiodarone is also safe and effective in controlling refractory tachyarrhythmias in infants and is safe after cardiac surgery.

The role of Doppler left ventricular filling indexes and Doppler tissue echocardiography in the assessment of cardiac involvement in hereditary hemochromatosis

Although cardiac dysfunction in hereditary hemochromatosis (HHC) can be evaluated by conventional echocardiography, findings are often not specific. To test the hypothesis that the assessment of (1) conventional Doppler left ventricular filling indexes and (2) intrinsic elastic properties of the myocardium by Doppler tissue echocardiography can both enhance the accuracy of echocardiographic diagnosis of cardiac involvement in HHC, a group of 18 patients with HHC (mean age 50+/-7 years) and 22 age-matched healthy subjects were studied. The following indexes were characteristic for HHC: (1) the duration of atrial reversal measured from pulmonary venous flow (ms) was longer(118+/-20 vs 90+/-16; P

Guideline-discordant care in acute myocardial infarction: predictors and outcomes

Objectives: To determine (i) factors which predict whether patients hospitalised with acute myocardial infarction (AMI) receive care discordant with recommendations of clinical practice guidelines; and (ii) whether such discordant care results in worse outcomes compared with receiving guideline-concordant care. Design: Retrospective cohort study. Setting: Two community general hospitals. Participants: 607 consecutive patients admitted with AMI between July 1997 and December 2000. Main outcome measures: Clinical predictors of discordant care; crude and risk-adjusted rates of inhospital mortality and reinfarction, and mean length of hospital stay. Results: At least one treatment recommendation for AMI was applicable for 602 of the 607 patients. Of these patients, 411(68%) received concordant care, and 191 (32%) discordant care. Positive predictors at presentation of discordant care were age > 65 years (odds ratio [OR], 2.5; 95% Cl, 1.7-3.6), silent infarction (OR, 2.7; 95% Cl, 1.6-4.6), anterior infarction (OR, 2.5; 95% Cl, 1.7-3.8), a history of heart failure (OR, 6.3; 95% Cl, 3.7-10.7), chronic atrial fibrillation (OR, 3.2; 95% Cl, 1.5-6.4); and heart rate greater than or equal to 100 beats/min (OR, 2.1; 95% Cl, 1.4-3.1). Death occurred in 12.0% (23/191) of discordant-care patients versus 4.6% (19/411) of concordant-care patients (adjusted OR, 2.42; 95% Cl, 1.22-4.82). Mortality was inversely related to the level of guideline concordance (P = 0.03). Reinfarction rates also tended to be higher in the discordant-care group (4.2% v 1.7%; adjusted OR, 2.5; 95% Cl, 0.90-7.1). Conclusions: Certain clinical features at presentation predict a higher likelihood of guideline-discordant care in patients presenting with AMI Such care appears to increase the risk of inhospital death.