Análise microscópica do miocárdio ventricular esquerdo em cães soropositivos para cinomose

Classificado no gênero Morbillivirus da família Paramixoviridae, o vírus da cinomose possui RNA de fita simples de polaridade negativa, é causador de doença multissistêmica, altamente contagiosa e grave dos cães e carnívoros selvagens, e com elevado índice de mortalidade em animais não vacinados ou com falhas vacinais. Com o objetivo de avaliar as alterações histopatológicas no coração, particularmente na região do miocárdio ventricular esquerdo, de cães naturalmente infectados com o vírus da cinomose, foram estudados 35 animais, de ambos os sexos e com idades variadas. Das 35 amostras enviadas ao Laboratório de Medicina Veterinária Preventiva do Hospital Veterinário de Uberaba, 100% (35/35) mostrou-se soropositivas para a cinomose (técnica de imunoensaio em fase sólida) e tiveram no miocárdio ventricular esquerdo as seguintes alterações histopatológicas: miocardite, degeneração hialina, hiperemia e hemorragia, com 42,8% (15/35), 31,4% (11/35), 14,3% (5/35) e 11,4% (4/35), respectivamente. Tendo utilizado o teste Qui-Quadrado com nível de significância de 0,05, conclui-se que existe alta correlação (p=0,02) entre os animais infectados com o vírus da cinomose e as alterações histopatológicas observadas no miocárdio ventricular esquerdo.

Percutaneous Coronary Intervention in Patients with Atrial Fibrillation: A Study of Factors Affecting Outcome, with a Special Emphasis on Periprocedural Antithrombotic Treatment

Antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is a delicate balancing between the risk of thromboembolism and the risk of bleeding. The purpose of this dissertation was to analyze current antithrombotic treatment strategies at the periprocedural stage and report outcomes in-hospital and at 1-month follow-up, and to evaluate the effect of renal impairment and predictive values of various bleeding scores on 1-year outcome after PCI in patients with AF. The first article was based on retrospective data from 7 Finnish hospitals between 2002–2006 (n=377), while the others were based on a prospective 17-center European register (AFCAS) gathered between 2008–2010 (n=963). The main findings in patients with AF undergoing PCI were: The use of glycoprotein IIb/IIIa inhibitors during PCI was associated with a four- to five-fold increase in the risk of major bleeding (I). Uninterrupted warfarin treatment did not increase perioperative complications and seemed to decrease bleeding complications compared to heparin bridging (II). Already mild renal impairment (eGFR 60–90mL/min) was associated with a 2.3-fold risk of all-cause mortality during the 12 months following PCI (III). Major adverse cardiac events occurred in 4.5% and bleeding complications in 7.1% of patients in the AFCAS register by 1-month follow-up (IV). In a study of patients in AFCAS register, all currently used bleeding risk scores were poor predictors of bleeding complications by 1-year follow-up (V). The findings will help improve treatment strategies for this fragile patient population with a high risk of bleeding and thrombotic complications.

Atrial natriuretic peptide and feeding activity patterns in rats

This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways

Release of plasma atrial natriuretic peptide after volume expansion is not related to pituitary-adrenal axis diurnal variation in normal subjects

The existence of a circadian rhythm of atrial natriuretic peptide (ANP) in humans is controversial. We studied the plasma ANP response to isotonic blood volume expansion in the morning and in the afternoon and its relationship with adrenocorticotropic hormone (ACTH)-cortisol diurnal variation in seven normal subjects. Basal plasma ANP level was similar in the morning (19.6 ± 2.4 pg/ml) and in the afternoon (21.8 ± 4.8 pg/ml). The ANP peak obtained with saline infusion (0.9% NaCl, 12 ml/kg) in the morning (49.4 ± 8 pg/ml) did not differ from that obtained in the afternoon (60.3 ± 10.1 pg/ml). There was no correlation between the individual mean cortisol and ACTH levels and the ANP peak obtained with saline infusion. These data indicate no diurnal variation in plasma ANP secretion induced by blood volume expansion and no relationship between plasma ANP peak and ACTH-cortisol diurnal variation

A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM) and for atrial natriuretic peptide (Km = 5 µM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.

Relationship between the actions of atrial natriuretic peptide (ANP), guanylin and uroguanylin on the isolated kidney

Guanylin and uroguanylin are peptides that bind to and activate guanylate cyclase C and control salt and water transport in many epithelia in vertebrates, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic effects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat kidney to identify possible synergisms between ANP, guanylin and uroguanylin. Inulin was added to the perfusate and glomerular filtration rate (GFR) was determined at 10-min intervals. Sodium was also determined. Electrolyte dynamics were measured by the clearance formula. Guanylin (0.5 µg/ml, N = 12) or uroguanylin (0.5 µg/ml, N = 9) was added to the system after 30 min of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min intervals to a control (N = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 µg/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 ± 0.86 to 64.62 ± 1.92, 120 min). In contrast, ANP blocked uroguanylin-induced increase in urine flow (from 0.21 ± 0.01 to 0.15 ± 0.007 ml g-1 min-1, 120 min, P<0.05) and the reduction in fractional sodium transport (from 72.04 ± 0.86 to 85.19 ± 1.48, %TNa+, at 120 min of perfusion, P<0.05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.

Nitrergic modulation of vasopressin, oxytocin and atrial natriuretic peptide secretion in response to sodium intake and hypertonic blood volume expansion

The central nervous system plays an important role in the control of renal sodium excretion. We present here a brief review of physiologic regulation of hydromineral balance and discuss recent results from our laboratory that focus on the participation of nitrergic, vasopressinergic, and oxytocinergic systems in the regulation of water and sodium excretion under different salt intake and hypertonic blood volume expansion (BVE) conditions. High sodium intake induced a significant increase in nitric oxide synthase (NOS) activity in the medial basal hypothalamus and neural lobe, while a low sodium diet decreased NOS activity in the neural lobe, suggesting that central NOS is involved in the control of sodium balance. An increase in plasma concentrations in vasopressin (AVP), oxytocin (OT), atrial natriuretic peptide (ANP), and nitrate after hypertonic BVE was also demonstrated. The central inhibition of NOS by L-NAME caused a decrease in plasma AVP and no change in plasma OT or ANP levels after BVE. These data indicate that the increase in AVP release after hypertonic BVE depends on nitric oxide production. In contrast, the pattern of OT secretion was similar to that of ANP secretion, supporting the view that OT is a neuromodulator of ANP secretion during hypertonic BVE. Thus, neurohypophyseal hormones and ANP are secreted under hypertonic BVE in order to correct the changes induced in blood volume and osmolality, and the secretion of AVP in this particular situation depends on NOS activity.

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

Chronic stimulation of sympathetic nervous activity contributes to the development and maintenance of hypertension, leading to left ventricular hypertrophy (LVH), arrhythmias and cardiac death. Moxonidine, an imidazoline antihypertensive compound that preferentially activates imidazoline receptors in brainstem rostroventrolateral medulla, suppresses sympathetic activation and reverses LVH. We have identified imidazoline receptors in the heart atria and ventricles, and shown that atrial I1-receptors are up-regulated in spontaneously hypertensive rats (SHR), and ventricular I1-receptors are up-regulated in hamster and human heart failure. Furthermore, cardiac I1-receptor binding decreased after chronic in vivo exposure to moxonidine. These studies implied that cardiac I1-receptors are involved in cardiovascular regulation. The presence of I1-receptors in the heart, the primary site of production of natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), cardiac hormones implicated in blood pressure control and cardioprotection, led us to propose that ANP may be involved in the actions of moxonidine. In fact, acute iv administration of moxonidine (50 to 150 µg/rat) dose-dependently decreased blood pressure, stimulated diuresis and natriuresis and increased plasma ANP and its second messenger, cGMP. Chronic SHR treatment with moxonidine (0, 60 and 120 µg kg-1 h-1, sc for 4 weeks) dose-dependently decreased blood pressure, resulted in reversal of LVH and decreased ventricular interleukin 1ß concentration after 4 weeks of treatment. These effects were associated with a further increase in already elevated ANP and BNP synthesis and release (after 1 week), and normalization by 4 weeks. In conclusion, cardiac imidazoline receptors and natriuretic peptides may be involved in the acute and chronic effects of moxonidine.

Mechanical cardiac remodeling and new-onset atrial fibrillation in long-term follow-up of subjects with chronic Chagas' disease

Atrial fibrillation (AF) affects subjects with Chagas' disease and is an indicator of poor prognosis. We investigated clinical, echocardiographic and electrocardiographic variables of Chagas' disease in a long-term longitudinal study as predictors of a new-onset AF episode lasting >24 h, nonfatal embolic stroke and cardiac death. Fifty adult outpatients (34 to 74 years old, 62% females) staged according to the Los Andes classification were enrolled. During a follow-up of (mean ± SD) 84.2 ± 39.0 months, 9 subjects developed AF (incidence: 3.3 ± 1.0%/year), 5 had nonfatal stroke (incidence: 1.3 ± 1.0%/year), and nine died (mortality rate: 2.3 ± 0.8%/year). The progression rate of left ventricular mass and left ventricular ejection fraction was significantly greater in subjects who experienced AF (16.4 ± 20.0 g/year and -8.6 ± 7.6%/year, respectively) than in those who did not (8.2 ± 8.4 g/year; P = 0.03, and -3.0 ± 2.5%/year; P = 0.04, respectively). In univariate analysis, left atrial diameter ≥3.2 cm (P = 0.002), pulmonary arterial hypertension (P = 0.035), frequent premature supraventricular and ventricular contraction counts/24 h (P = 0.005 and P = 0.007, respectively), ventricular couplets/24 h (P = 0.002), and ventricular tachycardia (P = 0.004) were long-term predictors of AF. P-wave signal-averaged ECG revealed a limited long-term predictive value for AF. In chronic Chagas' disease, large left atrial diameter, pulmonary arterial hypertension, frequent supraventricular and ventricular premature beats, and ventricular tachycardia are long-term predictors of AF. The rate of left ventricular mass enlargement and systolic function deterioration impact AF incidence in this population.

Biological significance of miR-126 expression in atrial fibrillation and heart failure

We investigated the biological significance of microRNA-126 (miR-126) expression in patients with atrial fibrillation (AF) and/or heart failure (HF) to examine the possible mechanism of miR-126-dependent AF and development of HF. A total of 103 patients were divided into three groups: AF group (18 men and 17 women, mean age: 65.62±12.72 years), HF group (17 men and 15 women, mean age: 63.95±19.71 years), and HF-AF group (20 men and 16 women, mean age: 66.56±14.37 years). Quantitative real-time PCR was used to measure relative miR-126 expression as calculated by the 2−ΔΔCt method. miR-126 was frequently downregulated in the 3 patient groups compared with controls. This reduction was significantly lower in permanent and persistent AF patients than in those with paroxysmal AF (P<0.05, t-test). Moreover, miR-126 expression was markedly lower in the HF-AF group compared with the AF and HF groups. The 3 patient groups had higher N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, lower left ventricular ejection fraction (LVEF), larger left atrial diameter, and higher cardiothoracic ratio compared with controls. There were significant differences in NT-proBNP levels and LVEF among the AF, HF, and HF-AF groups. Pearson correlation analysis showed that relative miR-126 expression was positively associated with LVEF, logarithm of NT-proBNP, left atrial diameter, cardiothoracic ratio, and age in HF-AF patients. Multiple linear regression analysis showed that miR-126 expression was positively correlated with LVEF, but negatively correlated with the logarithm of NT-pro BNP and the cardiothoracic ratio (all P<0.05). Serum miR-126 levels could serve as a potential candidate biomarker for evaluating the severity of AF and HF. However, to confirm these results, future studies with a larger and diverse patient population are necessary.

Contact force-guided catheter ablation for the treatment of atrial fibrillation: a meta-analysis of randomized, controlled trials

Contact force (CF) sensing technology allows real-time monitoring during catheter ablation for atrial fibrillation (AF). However, the effect of CF sensing technology on procedural parameters and clinical outcomes still needs clarification. Because of the inconsistent results thus far in this area, we performed a meta-analysis to determine whether CF sensing technology can improve procedural parameters and clinical outcomes for the treatment of AF. Studies examining the benefits of CF sensing technology were identified in English-language articles by searching the MEDLINE, Web of Science, and Cochrane Library databases (inception to May 2015). Ten randomized, controlled trials involving 1834 patients (1263 males, 571 females) were included in the meta-analysis (681 in the CF group, 1153 in the control group). Overall, the ablation time was significantly decreased by 7.34 min (95%CI=-12.21 to -2.46; P=0.003, Z test) in the CF group compared with the control group. CF sensing technology was associated with significantly improved freedom from AF after 12 months (OR=1.55, 95%CI=1.20 to 1.99; P=0.0007) and complications were significantly lower in the CF group than in the control group (OR=0.50, 95%CI=0.29 to 0.87; P=0.01). However, fluoroscopy time analysis showed no significantly decreased trend associated with CF-guided catheter ablation (weighted mean difference: -2.59; 95%CI=-9.06 to 3.88; P=0.43). The present meta-analysis shows improvement in ablation time and freedom from AF after 12 months in AF patients treated with CF-guided catheter ablation. However, CF-guided catheter ablation does not decrease fluoroscopy time.

Comportamento do índice de massa do ventrículo esquerdo de pacientes em diálise no decorrer de 17 anos

ResumoIntrodução:A hipertrofia ventricular esquerda (HVE) é alteração frequente em pacientes de diálise e imprime prognóstico sombrio. Não se conhece qual a tendência secular dessa alteração cardíaca em nossos pacientes.Objetivo:Avaliar o comportamento da HVE, pelo índice de massa do ventrículo esquerdo (IMVE), no decorrer de 17 anos em pacientes de um centro universitário de diálise, bem como verificar as possíveis causas desse comportamento.Métodos:Foi realizado um estudo longitudinal retrospectivo que avaliou, por meio de ecocardiografia, o IMVE em pacientes submetidos à hemodiálise em nosso Serviço de Diálise durante o período de 17 anos, de 1993 a 2010. Foram incluídos 250 exames de pacientes com doença renal crônica estágio V-D com idade superior a 18 anos que foram submetidos à avaliação ecocardiográfica de rotina.Resultados:Notou-se redução do IMVE à medida que os anos avançavam. Essa redução correlacionou-se à diminuição da pressão arterial e à elevação da hemoglobina. Em análise múltipla, a massa ventricular esquerda associou-se apenas à pressão arterial.Conclusão:A porcentagem de pacientes com HVE sofreu redução significante no decorrer de 17 anos em nossa Unidade de Diálise. O fator associado a essa redução foi a diminuição da pressão arterial.

Ventricular rate during acute atrial fibrillation and outcome of electrical cardioversion: The FinCV Study

The impact of ventricular rate (VR) on the outcome of electrical cardioversion (ECV) of acute atrial fibrillation (AF) is currently unknown. We aimed to determine the effect of VR during acute AF on the success of ECV, recurrence of AF and occurrence of post-cardioversion complications in 30 days follow-up. All ECVs performed in patients with acute atrial fibrillation lasting <48 hours in 2 Finnish university hospitals during 2003-2010 and 1 central hospital during 2010 were retrospectively identified. A total of 6,624 ECVs were performed in 2,821 consecutive patients. VR≤60 BPM was defined low and VR≥160 BPM high. The median VR before ECV was 109 BPM. The success rate of ECV was 94.2%. Bradycardia occurred in 62 (0.9%) and thromboembolic complications in 39 (0.6%) ECVs. Low VR was observed before 75 (1.1%) ECVs and male sex was its only independent predictor. High VR was observed in 165 (2.5%) ECVs. The independent predictors of high VR were younger age, <12 h episode duration, no previous history of AF and alcohol abuse. Low or high VR were not related to the success of ECV, incidence of thromboembolic or bradycardic complications, or recurrence of AF, although VR was significantly (p<0.001) lower in the patients in whom AF recurred. In conclusion, ECV of acute AF is an effective procedure and VR during AF does not affect its efficacy, the maintenance of sinus rhythm or the incidence of bradycardic, thromboembolic or other complications during 30 days follow-up after ECV. Low VR is predominately observed in male patients, while high VR was a feature related to a shorter history of AF and high alcohol-intake.