Relações pressão-diâmetro e esforço-diâmetro do ventrículo esquerdo em seres humanos. Padronização e análise crítica do método.

PURPOSE--To provide a critical analysis of the fluid filled manometric system and M-mode echocardiography and, by their association, to standardize the determination of left ventricular (LV) pressure-diameter and stress-diameter relationships in humans. MATERIAL AND METHODS--The pressure curve and the LV M-mode image was obtained in 24 patients with cardiopathy. The dynamic characteristics of the fluid-filled system have been studied to define the amplitude, the resonance and the time gap of the pressure curve register. The delay of the pressure curve recording was determined in all cases by comparing pressure curve and echocardiographic aortic valve registers. The values of pressure, diameter, posterior wall thickness and LV meridional stress was calculated at every 0.02s. RESULTS--Preliminary analyses of the fluid-filled manometric system indicated that this system has variable dynamic characteristics. The pressure-diameter and stress-diameter loops obtained were similar to those of the literature. The values of end-systolic stress, percentage of fractional shortening, ejection fraction and circumferential fiber shortening rate of patients with dilated cardiomyopathy (n = 5) were significantly reduced when compared to the values of patients without left ventricular overload (n = 8) and patients with ventricular volume overload. It has been verified, also, that the retard of the pressure curve record introduced by the fluid-filled manometric system does not modify the values of these variables. CONCLUSION--The LV pressure-diameter and stress-diameter relationships obtained by the association of echocardiography and LV manometry showed functional characteristics of the ventricle that could not appear by the use of the echocardiography or by the LV manometry themselves.

Mau Funcionamento do Sistema de Circulação Extracorpórea: Relato de Caso

Background and objectives: The introduction of extracorporeal circulation in clinical practice was decisive for the development of modern cardiovascular surgery. Addition of new procedures and equipment, however, brings inherent risks and complications. The objective of this report is to describe a malfunction of the oxygenation system and emphasize the importance of the interaction among the medical team members to prevent errors and complications. Case Report: During valve replacement and IVC correction surgery, we observed a darker shade of red in the blood on the exit of the oxygenator. Laboratory tests demonstrated severe acidosis and hypoxemia. The entire system was evaluated, but the cause of the malfunction was not found. Measures to reduce damage were successfully instituted. After the surgery, the whole system underwent technical evaluation. Conclusions: Interaction among the medical team members, early diagnosis, and immediate intervention were fundamental for a favorable outcome. © 2011 Elsevier Editora Ltda.

Insuficiência aórtica subcrônica e vias centrais relacionadas à regulação da ingestão de sódio

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência da dieta hiperlipídica ricas em ácidos graxos saturados sobre o metabolismo, estrutura e função cardíaca de ratos com estenose aórtica supravalvar

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Como estará a ingestão de sódio após uma sobrecarga de volume combinada ao tratamento com paroxetina?

Aortic regurgitation (AR) is still common in developing countries as secondary of rheumatic fever, and its incidence have increased in senile degenerative form. The AR develops severe myocardial hypertrophy. A common comorbidity associated with cardiovascular disease is depression. Among the most prescribed antidepressants in the world are the serotonin selective reuptake inhibitors (SSRIs). Central serotonergic pathways are involved with the inhibition of sodium intake and can be modify the excretion of this íon. Therefore, we investigated whether treatment with an antidepressants SSRI, the paroxetine, for four weeks can modfy the behavior of water and NaCl 0,3M intake, excretion of sodium and morphofunctional parameters of rats with AR induce. Wistar rats (280 - 300g) underwent surgery for AR (n=15) or control surgery (n=14). The AR was induced by retrograde puncture of valve leaflets. The animals were divided into 4 groups: AR + paroxetine (n=8), AR + control (n=7), control + paroxetine (n=7), control + control (n=7). From the 4th to the 8th week after inductuin of AR was administered paroxetine (10mg/kg pc) daily and subcutaneously. In the 4th and 8th week after induction of AR echocardiograms were performed to collect data morphofunctional. During the 4 weeks of treatment were analyzed intake of water and saline daily and once a week urine samples were collected for analysis by flame photometer of excretion of sodium and potassium. In the 10th week the animals were submitted to a challenge protocol hidromineral by combining furosemide (10 mg / kg bw) associated with the low dose of Captopril (5 mg / kg bw). During the challenged urine samples were collected for analysis by flame photometer of excretion of sodium and potassium at the time zero and after 2 hours of treatment. As a result we found that treatment with paroxetine in rats with AR determined an improvement in fractional shortening (shortening fraction: 52.7 ± 2.2% vs. RA ...

Antidepressivo modula o comportamento e a expressão gênica das cadeias de miosina, serca2 e fosfolambam em ratos com insuficiência aórtica?

Introduction: Aortic insufficiency (AoI), a volume overload, is characterized by the diastolic reflux of blood from the regurgitating aorta to the left ventricle. This effect results from malfunctioning aortic cusps. The main cause of AoI in developing countries is rheumatic fever, including Brazil, and valvar degeneration in developed countries. There is a strong association between cardiovascular diseases and depression. Selective serotonin reuptake inhibitors (SSRI) are one of the most prescribed antidepressants in the world. Previous studies of our laboratory showed that the utilization of a SSRI, paroxetine, improved cardiac function in rats with sub-chronic AoI and reduced the daily ingestion of hypertonic sodium (NaCl 0,3M). Cardiovascular diseases can determine behavior changes like increase of anxiety, and it is yet unknown if AoI would determine anxiety or anhedonia, incapacity of obtaining pleasure through physical or sensorial experiences. A possible target for SSRI action could be a change in the expression of enzyme isoforms that collaborate in the contractile function of the heart muscle, like the heavy chains of myosine, the sarcoplasmatic reticulum Ca2+/ATPase (SERCA) and its regulator protein, phospholamban (PLB). Objectives: Evaluation of behavior parameters for anxiety and anhedonia state and genic expression of a-myosine, b-myosine, SERCA2a and PLB in the heart tissue of rats with subchronic AoI that received treatment with an SSRI (paroxetine) for 4 weeks. Methods: Surgery to induce AoI was performed on male Wistar rats, anxiety was evaluated by the elevated plus-maze (EPM) and state of anhedonia was tested by ingestion of 2% sucrose solution. After euthanasia the heart tissue was collected and total RNA was extracted to be analyzed by the RT-qPCR method. Results: Heart fractional shortening was preserved in rats with AoI that were treated compared to rats with AoI that were not treated. There was no statistically ...

Multivariate analysis for animal selection in experimental research

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

Multivariate analysis for selecting animals for experimental research

Background Several researchers seek methods for the selection of homogeneous groups of animals in experimental studies, a fact justified because homogeneity is an indispensable prerequisite for casualization of treatments. The lack of robust methods that comply with statistical and biological principles is the reason why researchers use empirical or subjective methods, influencing their results. Objective To develop a multivariate statistical model for the selection of a homogeneous group of animals for experimental research and to elaborate a computational package to use it. Methods The set of echocardiographic data of 115 male Wistar rats with supravalvular aortic stenosis (AoS) was used as an example of model development. Initially, the data were standardized, and became dimensionless. Then, the variance matrix of the set was submitted to principal components analysis (PCA), aiming at reducing the parametric space and at retaining the relevant variability. That technique established a new Cartesian system into which the animals were allocated, and finally the confidence region (ellipsoid) was built for the profile of the animals’ homogeneous responses. The animals located inside the ellipsoid were considered as belonging to the homogeneous batch; those outside the ellipsoid were considered spurious. Results The PCA established eight descriptive axes that represented the accumulated variance of the data set in 88.71%. The allocation of the animals in the new system and the construction of the confidence region revealed six spurious animals as compared to the homogeneous batch of 109 animals. Conclusion The biometric criterion presented proved to be effective, because it considers the animal as a whole, analyzing jointly all parameters measured, in addition to having a small discard rate.

Efeito da inibição da NADPH oxidase sobre o estresse oxidativo e o fenótipo muscular esquelético de ratos com insuficiência cardíaca crônica induzida por estenose aórtica

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Efeito da inibição da NADPH oxidase sobre o estresse oxidativo e o fenótipo muscular esquelético de ratos com insuficiência cardíaca crônica induzida por estenose aórtica

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Infective endocarditis with left to right intracardiac fistula due to Streptococcus anginosus - a rare complication caused by an even rarer bacterium

Although infective endocarditis (IE) has been described in reports dating from the Renaissance, the diagnosis still challenges and the outcome often surprises. In the course of time, diagnostic criteria have been updated and validated to reduce misdiagnosis. Some risk factors and epidemiology have shown dynamic changes since degenerative valvular disease became more predominant in developed countries, and the mean age of the affected population increased. Despite streptococci have been being well known as etiologic agents, some groups, although rare, have been increasingly reported (e.g., Streptococcus milleri.) Intracardiac complications of IE are common and have a worse prognosis, frequently requiring surgical treatment. We report a case of a middle-aged diabetic man who presented with prolonged fever, weight loss, and ultimately severe dyspnea. IE was diagnosed based on a new valvular regurgitation murmur, a positive blood culture for Streptococcus anginosus, an echocardiographic finding of an aortic valve vegetation, fever, and pulmonary thromboembolism. Despite an appropriate antibiotic regimen, the patient died. Autopsy findings showed vegetation attached to a bicuspid aortic valve with an associated septal abscess and left ventricle and aortic root fistula connecting with the pulmonary artery. A large thrombus was adherent to the pulmonary artery trunk and a pulmonary septic thromboemboli were also identified.

Nuove acquisizioni in termini di insufficienza mitralica: complicanze tromboemboliche dopo chirurgia della valvola mitrale: incidenza, predittori e implicazioni cliniche

Objectives: to define in patients undergoing surgery for mitral regurgitation (MR) the risk of thrombo-embolic complications, particularly ischemic stroke (IS) compared to that in the general population. Background: MR is frequent, occurs mostly in the elderly and guidelines recommend surgery in asymptomatic patients but IS risks are unknown. Methods: in 1344 patients (65±12 years) consecutively operated for MR (procedures: 897 valve repair, MRep; 447 valve replacement, 231 mechanical, MVRm; 216 biological, MVRb), thrombo-embolic complications particularly IS (diagnosed by a neurologist) during follow-up were assessed early (<30 days), mid-term (30-180 days) and long-term (180 days). Results: IS occurred in 130 patients and IS or transient ischemic attack in 201. IS rates were 1.9±0.4% and 2.7±0.5%, at 30 and 180 days and 8.1±0.8% at 5 years. IS rates were lowest after MRep vs. MVRb and MVRm (6.1±0.9, 8±2.1 and 16.1±2.7% at 5 years, p<0.001). Comparison to IS expected rates in the population showed high risk within 30 days of surgery (Risk-ratio 41[26-60], p<0.001 but p>0.10 between procedures) and moderate risk after 30 days (risk-ratio 1.7 overall, p<0.001; 1.3 for MRep, p=0.07; 0.98 for MVRb, p=0.95; 4.8 for MVRm, p<0.001). Beyond 180 days, IS risk declined further and was not different from the general population for MRep (1.2, p=0.30) and for MVRb (0.9, p=0.72). Risk of IS or transient ischemic attack was higher than the general population in all groups up to 180 days. The risk of bleeding beyond 30 days was lowest in MRep vs. MVRb and MVRm (7±1, 14±4 and 16±3% at 10 years, p<0.001). Conclusion: thrombo-embolic complications after MR surgery are both reason for concern and encouragement. IS risk is notable early, irrespective of the procedure performed, but long-term is not higher than in the general population after MRep and MVRb. Preference for MRep should be emphasized and trials aimed at preventing IS should be conducted to reduce the thrombo-embolic and hemorrhagic risk in patients undergoing surgery for MR.

The medical management after surgery for advanced heart failure

The aim of the Research of this Ph D Project is to improve the medical management after surgery for advanced heart failure, both after left ventricular assist devices (LVAD) implantation, and after heart transplantation in the long-term. Regarding heart transplantation (HTx), the Research Project is focused on diagnostics, classification, prevention and treatment of cardiac allograft vasculopathy (CAV), and on treatment of post-HTx cancers; the results are presented in the first part of this Thesis. In particular, the main aspect investigated are the prognostic role of information derived from coronary angiography, coronary tomography and intravascular ultrasound, and the different sensitivity of these techniques in predicting outcomes and in diagnosing CAV. Moreover, the role of mTOR inhibitors on CAV prevention or treatment is investigated, both alone and in combination with different anti-CMV prevention strategies, as well as the impact of mTOR inhibitors on clinical outcomes in the long term. Regarding LVAD, the main focus is on the role of transthoracic echocardiography in the management of patients with a continuous-flow, centrifugal, intrapericardial pump (HVAD, Heartware); this section is reported in the second part of this Thesis. The main aspects investigated are the use of echocardiography in patients with HVAD device and its interaction with the information derived from pump curves' analysis in predicting aortic valve opening status, a surrogate of the condition of support provided by the LVAD.

Studio sul ruolo dei fattori genetici coinvolti nella Valvola Aortica Bicuspide e/o nell'Aneurisma dell'Aorta Toracica

La Valvola Aortica Bicuspide (BAV) rappresenta la più comune anomalia cardiaca congenita, con un’incidenza dello 0,5%-2% nella popolazione generale. Si caratterizza per la presenza di due cuspidi valvolari anziché tre e comprende diverse forme. La BAV è frequentemente associata agli aneurismi dell’aorta toracica (TAA). La dilatazione dell’aorta espone al rischio di sviluppare le complicanze aortiche acute. Materiali e metodi Sono stati reclutati 20 probandi consecutivi sottoposti a chirurgia della valvola aortica e dell'aorta ascendente presso l'Unità di Chirurgia Cardiaca di Policlinico S.Orsola-Malpighi di TAA associata a BAV. Sono stati esclusi individui con una condizione sindromica predisponente l’aneurisma aortico. Ciascun familiare maggiorenne di primo grado è stato arruolato nello studio. L’analisi di mutazioni dell’intero gene ACTA2 è stata eseguita con la tecnica del “bidirectional direct sequencing”. Nelle forme familiari, l’intera porzione codificante del genoma è stata eseguita usando l’exome sequencing. Risultati Dopo il sequenziamento di tutti i 20 esoni e giunzioni di splicing di ACTA2 nei 20 probandi, non è stata individuata alcuna mutazione. Settantasette familiari di primo grado sono stati arruolati. Sono state identificate cinque forme familiari. In una famiglia è stata trovata una mutazione del gene MYH11 non ritenuta patogenetica. Conclusioni La mancanza di mutazioni, sia nelle forme sporadiche sia in quelle familiari, ci suggerisce che questo gene non è coinvolto nello sviluppo della BAV e TAA e, l’associazione che è stata riportata deve essere considerata occasionale. L’architettura genetica della BAV verosimilmente dovrebbe consistere in svariate differenti varianti genetiche che interagiscono in maniera additiva nel determinare un aumento del rischio.