Efeitos do treinamento físico aeróbico sobre a expressão da miostatina e o trofismo de músculos esqueléticos e cardíaco de ratos espontaneamente hipertensos com insuficiência cardíaca

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ultrasound analysis of a canine patient with renal disease and chronic liver disease undergoing treatment with intravenous stem cells

With the improvement in quality of life of animals, it is increasingly frequent clinical care of elderly patients, which present renal disorders, including chronic renal failure. Recent studies report the use of stem cells to treat renal failure, which would improve the levels of urea and creatinine, and in renal ultrasound evaluation. With the present work, the idea is to report a case of ultrasonographic evaluation in a patient with chronic renal failure, liver disease and splenic nodule, which underwent stem cell therapy, where there was an improvement in the sonographic evaluation of part of the liver.

Portal hypertension in dogs

Portal hypertension (PH) is the pathological increase in portal vein pressure above normal limits. Two variables control the pressure in the portal system: the resistance to blood flow and blood flow volume in the portal system. If one these variables changes, PH may develop. Classification: Pre-hepatic (e. g. compression of the portal vein), intrahepatic (e. g. chronic hepatitis and cirrhosis) or post-hepatic (e. g. right heart failure). The invasive methods (intravenous catheter) were replaced by an indirect method of diagnosis: Doppler Ultrasound. This technique does not measure portal pressure, but indirectly allows the diagnosis of PH. Average speed of portal flow decrease (<10 cm/s) and hepatofugal flow have been reported in cirrhotic dogs with PH. Currently, the focus of the ultrasound is the detection of acquired collateral portal circulation (ACPC), closely correlated with hepatic encephalopathy. The characterization of these vessels is essential to differentiate them from congenital shunts. They are usually multiple vessels, small and tortuous, with turbulent flow, near to the kidneys, and/or a single and larger vessel, draining into the left renal vein (dilated gonadal vein). Gastric, esophageal and mesenteric varices may occur. After identifying the PH, it is important to determine its origin in order to treat the underlying disease. B-Mode Ultrasound and Doppler are the best choices in cases of suspected PH, because they may recognize not just the hypertension, but also its complications and origin.

Influência do exercício físico no remodelamento cardíaco de ratos espontaneamente hipertensos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Coronary to Bronchial Artery Fistula: Are We Treating it Right?

Fistulas between coronary artery and bronchial artery may be present from birth, with few hemodynamic consequences, and may remain closed due to similarity of the filling pressures at these 2 sites.(1) They can also be secondary to pulmonary artery occlusive disease or chronic pulmonary inflammation.(2,3) These pulmonary changes may cause a dilation of the fistula and make it functional, causing angina pectoris by coronary steal syndrome, which is the most common symptom. The presentation may also be composed of episodes of hemoptysis, heart failure, and infective endocarditis. However, most patients remain asymptomatic. The ones that need treatment may not have a good response to the medical management, requiring an intervention. This can be done using embolization coils, stents grafts, and performing surgical ligation of the fistulas.(2-4) J INVASIVE CARDIOL 2012;24(11):E303-E304

Risk Factor Analysis of Late Survival After Heart Transplantation According to Donor Profile: A Multi-Institutional Retrospective Study of 512 Transplants

Introduction. Patients with terminal heart failure have increased more than the available organs leading to a high mortality rate on the waiting list. Use of Marginal and expanded criteria donors has increased due to the heart shortage. Objective. We analyzed all heart transplantations (HTx) in Sao Paulo state over 8 years for donor profile and recipient risk factors. Method. This multi-institutional review collected HTx data from all institutions in the state of Sao Paulo, Brazil. From 2002 to 2008 (6 years), only 512 (28.8%) of 1777 available heart donors were accepted for transplantation. All medical records were analyzed retrospectively; none of the used donors was excluded, even those considered to be nonstandard. Results. The hospital mortality rate was 27.9% (n = 143) and the average follow-up time was 29.4 +/- 28.4 months. The survival rate was 55.5% (n = 285) at 6 years after HTx. Univariate analysis showed the following factors to impact survival: age (P = .0004), arterial hypertension (P = .4620), norepinephrine (P = .0450), cardiac arrest (P = .8500), diabetes mellitus (P = .5120), infection (P = .1470), CKMB (creatine kinase MB) (P = .8694), creatinine (P = .7225), and Na+ (P = .3273). On multivariate analysis, only age showed significance; logistic regression showed a significant cut-off at 40 years: organs from donors older than 40 years showed a lower late survival rates (P = .0032). Conclusions. Donor age older than 40 years represents an important risk factor for survival after HTx. Neither donor gender nor norepinephrine use negatively affected early survival.

Exercise Training Decreases Adipose Tissue Inflammation in Cachectic Rats

Bearing in mind that cancer cachexia is associated with chronic systemic inflammation and that endurance training has been adopted as a nonpharmacological anti-inflammatory strategy, we examined the effect of 8 weeks of moderate intensity exercise upon the balance of anti-and pro-inflammatory cytokines in 2 different depots of white adipose tissue in cachectic tumour-bearing (Walker-256 carcinosarcoma) rats. Animals were assigned to a sedentary control (SC), sedentary tumour-bearing (ST), sedentary pair-fed (SPF) or exercise control (EC), exercise tumour-bearing (ET), and exercise pair-fed (EPF) group. Trained rats ran on a treadmill (60% VO(2)max) 60 min/day, 5 days/week, for 8 weeks. The retroperitoneal (RPAT) and mesenteric (MEAT) adipose pads were excised and the mRNA (RT-PCR) and protein (ELISA) expression of IL-1 beta, IL-6, TNF-alpha, and IL-10 were evaluated. The number of infiltrating monocytes in the adipose tissue was increased in cachectic rats. TNF-alpha mRNA in MEAT was increased in the cachectic animals (p < 0.05) in relation to SC. RPAT protein expression of all studied cytokines was increased in cachectic animals in relation to SC and SPF (p < 0.05). In this pad, IL-10/TNF-alpha ratio was reduced in the cachectic animals in comparison with SC (p < 0.05) indicating inflammation. Exercise training improved IL-10/TNF-alpha ratio and induced a reduction of the infiltrating monocytes both in MEAT and RPAT (p < 0.05), when compared with ST. We conclude that cachexia is associated with inflammation of white adipose tissue and that exercise training prevents this effect in the MEAT, and partially in RPAT.

The Real Importance of Pre-Existing Comorbidities on Long-Term Mortality after Acute Kidney Injury

Background: The causes of death on long-term mortality after acute kidney injury (AKI) have not been well studied. The purpose of the study was to evaluate the role of comorbidities and the causes of death on the long-term mortality after AKI. Methodology/Principal Findings: We retrospectively studied 507 patients who experienced AKI in 2005-2006 and were discharged free from dialysis. In June 2008 (median: 21 months after AKI), we found that 193 (38%) patients had died. This mortality is much higher than the mortality of the population of Sao Paulo City, even after adjustment for age. A multiple survival analysis was performed using Cox proportional hazards regression model and showed that death was associated with Khan's index indicating high risk [adjusted hazard ratio 2.54 (1.38-4.66)], chronic liver disease [1.93 (1.15-3.22)], admission to non-surgical ward [1.85 (1.30-2.61)] and a second AKI episode during the same hospitalization [1.74 (1.12-2.71)]. The AKI severity evaluated either by the worst stage reached during AKI (P=0.20) or by the need for dialysis (P=0.12) was not associated with death. The causes of death were identified by a death certificate in 85% of the non-survivors. Among those who died from circulatory system diseases (the main cause of death), 59% had already suffered from hypertension, 34% from diabetes, 47% from heart failure, 38% from coronary disease, and 66% had a glomerular filtration rate <60 previous to the AKI episode. Among those who died from neoplasms, 79% already had the disease previously. Conclusions: Among AKI survivors who were discharged free from dialysis the increased long-term mortality was associated with their pre-existing chronic conditions and not with the severity of the AKI episode. These findings suggest that these survivors should have a medical follow-up after hospital discharge and that all efforts should be made to control their comorbidities.

Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system

Background. Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. Methods. Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V + normal-phosphorus diet (np)) and 'Nx + PTx': G2 (nPTH + pP), G3 (nPTH + rP), G4 (hPTH + pP) and G5 (hPTH + rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, alpha-actin, transforming growth factor-beta (TGF-beta) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. Results. Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-beta, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of alpha-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. Conclusion. In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.

Le caratteristiche delle modalità organizzative della medicina territoriale nella gestione della patologia cronica. Il caso di studio dell’azienda Ausl di Bologna

L’aumento dei costi in sanità, l’aumentata prevalenza delle patologie croniche, le disuguaglianze attuali, evidenziano la domanda crescente di una popolazione fragile che richiede una risposta globale ai bisogni della persona nel suo insieme, attraverso la costruzione di un sistema sanitario integrato che ne garantisca una presa in carico efficace. Riuscire a gestire le patologie croniche in modo appropriato è la sfida a cui sono chiamati i professionisti socio-sanitari; ma quali sono gli elementi per riuscirci? Le evidenze scientifiche dimostrano che è fondamentale l’integrazione tra i professionisti e lo sviluppo dei Percorsi Diagnostici Terapeutici Assistenziali (PDTA). In quest’ottica, in Italia e in particolare in Emilia-Romagna e nell’Azienda USL di Bologna si sono succeduti, e ancora si stanno evolvendo, diversi modelli di organizzazione per migliorare la gestione appropriata delle patologie croniche e l’aderenza alle linee guida e/o ai PDTA. Il ruolo del medico di medicina generale (MMG) è ancora fondamentale e il suo contributo integrato a quello degli gli altri professionisti coinvolti sono imprescindibili per una buona gestione e presa in carico del paziente cronico. Per questo motivo, l’Azienda USL di Bologna ha sviluppato e implementato una politica strategica aziendale volta a disegnare i PDTA e incoraggiato la medicina generale a lavorare sempre di più in gruppo, rispetto al modello del singolo medico. Lo studio ha individuato nelle malattie cardiovascolari, che rimangono la causa principale di morte e morbilità, il suo focus prendendo in esame, in particolare,lo scompenso cardiaco e il post-IMA. L’obiettivo è verificare se e quanto il modello organizzativo, le caratteristiche del medico e del paziente influiscono sul buon management delle patologie croniche in esame valutando la buona adesione alla terapia farmacologica raccomandata dalle linee guida e/o PDTA dello scompenso cardiaco e post-IMA.

Utilzzo dei parametri ecocardiografici tradizionali ed a Doppler tissutale nella valutazione della disfunzione atrio-ventricolare in cani affetti da malattia mitralica cronica

In questo lavoro ci siamo posti come obiettivo lo studio della disfunzione atrio-ventricolare mediante tecniche ecocardiografiche avanzate (come il Tissue Doppler Imaging - TDI) in cani affetti da malattia mitralica cronica (MVD). Una prima parte è volta alla valutazione della funzionalità diastolica del ventricolo destro. Ci siamo proposti di analizzare la funzione del ventricolo destro in cani affetti da malattia del cuore sinistro per comprendere se quest’ultima possa condizionare direttamente la performance del settore cardiaco controlaterale. I risultati più importanti che abbiamo riscontrato sono: l’assenza di differenze significative nella disfunzione sisto-diastolica del ventricolo destro in cani con MVD a diverso stadio; la diretta correlazione tra le variabili TDI di funzionalità del ventricolo destro con il grado di disfunzione del ventricolo sinistro, come indicatori di interdipendenza ventricolare; ed infine il riscontro di una maggior tendenza ad alterazioni diastoliche del ventricolo sinistro in cani con ipertensione polmonare. A quest’ultimo proposito, per quanto riguarda le variabili TDI, il rapporto E/e’ dell’anulus mitralico laterale e settale è risultato avere una differenza significativa tra i cani con ipertensione polmonare e quelli privi di ipertensione polmonare (P<0,01). Nel secondo studio abbiamo applicato il TDI per l’analisi della funzione sisto-diastolica dell’atrio sinistro. Il lavoro è stato articolato in una parte di validazione della metodica su cani normali ed una su animali affetti da MDV. I risultati ottenuti mostrano che la valutazione ecocardiografica delle proprietà di deformazione dell’atrio sinistro basata sul TDI è attuabile e riproducibile nel cane. Abbiamo fornito dei valori di normalità per questa specie e confrontato questi dati con quelli ricavati in cani portatori di MVD. Le differenza tra le varie classi di malattia, nei diversi gradi di dilatazione atriale, sono risultate limitate, ma abbiamo individuato delle correlazioni tra i parametri TDI ed alcune variabili di funzionalità atriale.

Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR) to cardiovascular health outcomes. Secondary prevention through exercise-based CR is the intervention with the best scientific evidence to contribute to decrease morbidity and mortality in coronary artery disease, in particular after myocardial infarction but also incorporating cardiac interventions and chronic stable heart failure. The present position paper aims to provide the practical recommendations on the core components and goals of CR intervention in different cardiovascular conditions, to assist in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of CR. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, national or individual centre level, need to consider where and how structured programmes of CR can be delivered to all patients eligible. Thus a novel, disease-oriented document has been generated, where all components of CR for cardiovascular conditions have been revised, presenting both well-established and controversial aspects. A general table applicable to all cardiovascular conditions and specific tables for each clinical disease have been created and commented.

Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: complex congenital cardiac lesions

With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death. Medical aspects that need to be considered relate to the long-term and multisystemic effects of single ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part III of the guidelines includes recommendations for the care of patients with complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Fontan operations and single ventricles, Eisenmenger's syndrome, and cyanotic heart disease. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.