Stress-triggered synaptic malfunction: a gate along the path from depressionto dementia

Tese de Doutoramento em Ciências da Saúde.

Evaluation of the heart rate and arrhythmias following the Maze procedure for chronic atrial fibrillation

PURPOSE: To assess the presence and the prevalence of arrhythmias and the variability of the heart rate in the medium-term postoperative period following the maze procedure for chronic atrial fibrillation (AF). METHODS: Seventeen patients with a mean age of 51.7±12.9 years, who previously underwent the maze procedure without cryoablation for chronic atrial fibrillation, were evaluated with the 24 hour electrocardiogram (ECG) - Holter monitoring from the 6th month after the operation. Valvular and coronary procedures were concomitantly performed. RESULTS: The mean heart rate during Holter monitoring was 82±8bpm; the maximal heart rate was 126 ± 23bpm and the minimal heart rate 57±7bpm. Sinus rhythm was found in 10 (59%) patients and atrial rhythm was found in 7 (41%). Supraventricular extrasystoles had a rate of 2.3±5.5% of the total number of heartbeats and occurred in 16 (94%) patients. Six (35%) patients showed nonsustained atrial tachycardia. Ventricular extrasystoles, with a rate of 0.8±0.5% of the total heartbeats, occurred in 14 (82%) patients. The chronotropic competence was normal in 9 (53%) patients and attenuated in 8 (47%). The atrioventricular conduction (AV) was unchanged in 13 (76%) patients and there were 4 (24%) cases of first degree atrioventricular block (AVB). CONCLUSION: After the maze procedure, the values for the mean heart rate, AV conduction and chronotropic competence approach the normal range, although some cases show attenuation of the chronotropic response, first degree AV block or benign arrhythmias.

Holt-Oram syndrome revisited. Two patients in the same family

Holt-Oram syndrome was first described in 1960 as an association of familial heart disease and musculoskeletal abnormalities. The most important findings include atrial septal defects, atrioventricular conduction abnormalities, vascular hypoplasia, and upper limb musculoskeletal deformities. We report two patients with this syndrome in the same family and discuss the variability of the musculoskeletal abnormalities and their association with the cardiac morphologic defects. Both patients in this study had associated eosinophilia, which has not been reported in the literature.

Bundle branch and atrioventricular block as complications of acute myocardial infarction in the thrombolytic era

OBJECTIVE: To analyze the incidence of intraventricular and atrioventricular conduction defects associated with acute myocardial infarction and the degree of in hospital mortality resulting from this condition during the era of thrombolytic therapy. METHODS: Observational study of a cohort of 929 consecutive patients with acute myocardial infarction. Multivariate analysis by logistic regression. Was used. RESULTS: Logistic regression showed a greater incidence of bundle branch block in male sex (odds ratio = 1.87, 95% CI = 1.02-3.42), age over 70 years (odds ratio = 2.31, 95% CI = 1.68-5.00), anterior localization of the infarction (odds ratio = 1.93, 95% CI = 1.03-3.65). There was a greater incidence of complete atrioventricular block in inferior infarcts (odds ratio = 2.59, 95% CI 1.30-5.18) and the presence of cardiogenic shock (odds ratio = 3.90, 95% CI = 1.43-10.65). Use of a thrombolytic agent was associated with a tendency toward a lower occurrence of bundle branch block (odds ratio = 0.68) and a greater occurrence of complete atrioventricular block (odds ratio = 1.44). The presence of bundle branch block (odds ratio = 2.45 95% , CI = 1.14-5.28) and of complete atrioventricular block (odds ratio = 13.59, 95% CI = 5.43-33.98) was associated with a high and independent probability of inhospital death. CONCLUSION: During the current era of thrombolytic therapy and in this population, intraventricular disturbances of electrical conduction and complete atrioventricular block were associated with a high and independent risk of inhospital death during acute myocardial infarction.

Atrial activation during sinus rhythm in patients with rheumatic and non-rheumatic paroxysmal atrial fibrillation. Frequency-domain analysis using signal-averaged electrocardiography

OBJECTIVE: Using P-wave signal-averaged electrocardiography, we assessed the patterns of atrial electrical activation in patients with idiopathic atrial fibrillation as compared with patterns in patients with atrial fibrillation associated with structural heart disease. METHODS: Eighty patients with recurrent paroxysmal atrial fibrillation were divided into 3 groups as follows: group I - 40 patients with atrial fibrillation associated with non-rheumatic heart disease; group II - 25 patients with rheumatic atrial fibrillation; and group III - 15 patients with idiopathic atrial fibrillation. All patients underwent P-wave signal-averaged electrocardiography for frequency-domain analysis using spectrotemporal mapping and statistical techniques for detecting and quantifying intraatrial conduction disturbances. RESULTS: We observed an important fragmentation in atrial electrical conduction in 27% of the patients in group I, 64% of the patients in group II, and 67% of the patients in group III (p=0.003). CONCLUSION: Idiopathic atrial fibrillation has important intraatrial conduction disturbances. These alterations are similar to those observed in individuals with rheumatic atrial fibrillation, suggesting the existence of some degree of structural involvement of the atrial myocardium that cannot be detected with conventional electrocardiography and echocardiography.

Ventricular resynchronization through biventricular cardiac pacing for the treatment of refractory heart failure in dilated cardiomyopathy

OBJECTIVE: The biventricular pacing (BVP) approach has good results in the treatment of congestive heart failure (CHF) in patients (pts) with disorders of intraventricular conduction. METHODS: We have applied BVP to 28 pts, with left ventricular pacing using minitoracotomy in 3 pts and the transvenous aproach via coronary sinus in 25 pts. The mean duration of the QRS complexes was 187 ms, in the presence of the left branch block in 22 pts, and right branch block + divisional hemiblock in 6 pts. All pts had been considerated candidates to cardiac transplantation, and were under optimized drug therapy. Sixteen pts were in Functional Class (NYHA) IV, and 12 in class III. The ejection fraction varied from 22 to 46% (average = 34%). The pacing mode employed was biventricular triple-chamber in 22 pts, and bi-ventricular dual-chamber in 6 pts (one with ICD). RESULTS: The pts were followed up for a period that ranged from 10 days to 14 months (mean 5 months). All pts presented clinical improvement after implant, chaging the NYHA Functional Class at the end of follow-up to Class I (9pts), Class II (10 pts) and Class III (6 pts). The initial mean ejection fraction have-raised to 37%. Two pts died suddenly. One patient died due to a pulmonary fungal infection. CONCLUSION: Ventricular resynchronization through BVP, improved significantly the Functional Class and, therefore, the quality of life. Assessments of myocardial function acutely performed do not reflect the clinical improvement observed.

Noninvasive cardiac assessment in children of women with systemic lupus erythematosus

OBJECTIVE: Noninvasive cardiac assessment of newborns and infants of women with systemic lupus erythematosus. The children had no congenital total atrioventricular block and were compared with the children of healthy women. METHODS: We prospectively assessed 13 newborns and infants aged 1 to 60 days, children of women with systemic lupus erythematosus and without congenital total atrioventricular block. These children were compared with 30 children of women who had no lupus or anti-Ro/SSA antibodies, and no risk factors for congenital heart disease either. Their age groups matched. The following examinations were performed: cardiological physical examination, electrocardiography, echocardiography, and signal-averaged electrocardiography. RESULTS: The statistical analysis showed no significant difference in ventricular function or in the cardiac conduction system between the groups. CONCLUSION: In regard to the conduction system and ventricular function in the absence of total atrioventricular block, no statistically significant difference was observed between the children of women with systemic lupus erythematosus and children of healthy women.

Female alcoholics: electrocardiographic changes and associated metabolic and electrolytic disorders

OBJECTIVE: To identify the electrocardiographic changes and their associations with metabolic and electrolytic changes in female alcoholics. METHODS: The study comprised 44 female alcoholics with no apparent physical disorder. They underwent the following examinations: conventional electrocardiography; serologic tests for syphilis, Chagas' disease, and hepatitis B and C viruses; urinary pregnancy testing; hematimetric analysis; biochemical measurements of albumin, fibrinogen, fasting and postprandial glycemias, lipids, hepatic enzymes, and markers for tissue necrosis and inflammation. RESULTS: Some type of electrocardiographic change was identified in 33 (75%) patients. In 17 (38.6%) patients, more than one of the following changes were present: prolonged QTc interval in 24 (54.5%), change in ventricular repolarization in 11(25%), left ventricular hypertrophy in 6 (13.6%), sinus bradycardia in 4 (9.1%), sinus tachycardia in 3 (6.8%), and conduction disorder in 3 (6.8%). The patients had elevated mean serum levels of creatine phosphokinase, aspartate aminotransferases, and gamma glutamyl transferase, as well as hypocalcemia and low levels of total cholesterol and LDL-cholesterol. The patients with altered electrocardiograms had a more elevated age, a lower alcohol consumption, hypopotassemia, and significantly elevated levels of triglycerides, postprandial glucose, sodium and gamma glutamyl transferase than those with normal electrocardiograms. The opposite occurred with fasting glycemia, magnesium, and alanine aminotransferase. CONCLUSION: The electrocardiographic changes found were prolonged QTc interval, change in ventricular repolarization, and left ventricular hypertrophy. Patients with normal and abnormal electrocardiograms had different metabolic and electrolytic changes.

Frequency of hypertension in chronic Chagas' disease: retrospective clinical study

OBJECTIVE: To assess the frequency of hypertension in chagasic patients, as well as its clinical behavior and cardiologic findings. METHODS: We carried out a retrospective study with 225 patients with chronic Chagas' disease and hypertension (104 males), mean age of 55.1 ± 11.8. These patients were being followed up in the outpatient care clinics from 1984 to 2000. The study assessed the clinical, electrocardiographic, and radiological viewpoints. RESULTS: Of the 225 hypertensive patients (prevalence = 33.3%), 78 (34.7%) had mild hypertension, 108 (48%) had moderate hypertension, and 39 (17.3%) had severe hypertension. The association of left anterosuperior divisional block and right bundle-branch block occurred in 39 cases (17.3%), and enlargement of the cardiac area on radiological examination occurred in 93 (44.9%) of the 207 cases studied. The undetermined form of Chagas' disease was the most prevalent, 30.2% of the cases, followed by the form associated with conduction disorders in 27.1%, and the isolated form of conduction disorders in 21.3%. CONCLUSION: Chagasic patients had a frequency of hypertension similar to that of the general population, and the clinical profile of the hypertensive chagasic patients seemed not to differ a lot from that of the chagasic patients.

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001). Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients

Background: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG) is a stratification method in the risk of rejection. Objective: To develop a risk score for rejection, using SAECG variables. Methods: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without). In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without). Results: On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02). Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03) and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03). We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01), assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. Conclusion: The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies.

Miocardite no macaco Cebus após inoculações repetidas com Schizotrypanum cruzi

Transmission of Chagas disease is realized through contamination of ocular conjunctiva, mucosa or skin with infected dejections eliminated by the insect vectors of Schizotrypanum cruzi (Triatoma infestans, Panstrongylus megistus and Rhodnius prolixus). The triatomid bugs live in holes and craks in the walls, in beds, behind trunks, etc. Found in primitive mud huts covered with thatched roofs, and so the human dwellers have many chances to contract the disease, reinfections being reasonably more to expect than a single inoculation. Experimental work reproducing those natural conditions is welcomed as some important features in the pathologic picture of the disease such as the extensive myocardial fibrosis seen in chronic cases are still incompletely known. Microscopic changes were studied in the heart muscle of seven Cebus monkeys infected by S. cruzi. This animal survives the acute stage of the disease and so is particularly suited to experiments of long duration in which several inoculations of S. cruzi are performed. Three different strains of S. cruzi isolated from acute cases of Chagas' disease were employed. One monkey was injected in the skin with infected blood and necropsied after 252 days. Two monkeys were three times, and one, eight times infected in skin, one of them with contaminated blood, and two with contaminated blood and dejections from infected bugs. The necropsies were performed after 35, 95 and 149 days. One monkey was three times inoculated through the intact ocular conjunctiva (one time with infected blood, two times with dejections from infected bugs), and one time through the wounded buccal mucosa, and necropsied after 134 days. Another monkey was six times inoculated, four times through the intact ocular conjunctiva (one time with contaminated blood, three times with dejections from infected bugs) and two times injected in the skin with infected blood, and necropsied after 157 days. Finally, another monkey was nine times inoculated, four times through the intact ocular conjunctiva (one time with infected blood, and three times with dejections from infected bugs), and five times injected in the skin (four times with contaminated blood, and one time with dejections from infected bugs), and necropsied after 233 days. The microscopic picture was uniform presenting, however, considerable individual variations, and was represented by diffuse interstitial myocarditis, frequently more (marked in the right ventricle base of the heart), accompanied by lymphatic stasis. The infiltration consists of macrophages, plasma cells and lymphocytes, the cellular reaction having sometimes a perivascular distribution, involving the auriculo-ventricular system of conduction, endocardium, epicardium and cardiac sympathetic gangliae. The loss of cardiac muscle fibers was always minimal. Leishmanial forms of S. cruzi in myocardial fibers are scanty and, in two cases, absent. Fatty necrosis in the epicardium was noted in two cases. Obliterative changes of medium-sized branches of coronary arteries (hypersensitivity reaction?) and multiple infarcts of the myocardium was found in one instance. The diffuse myocarditis induced by S. cruzi in several species of monkeys of the genus Cebus observed after 233 days (several inoculations) and 252 days (single inoculation) is not associated with disseminated fibrosis such as is reported in chronic cases of Chagas' disease. Definite capacity of reversion is another characteristic of the interstitial myocarditis observed in the series of Cebus monkeys here studied. The impression was gained that repeated inoculation with S. cruzi may influence the myocardial changes differently according to the period between the reinoculations. A short period after the first inoculation is followed by more marked changes, while long periods are accompanied by slight changes, which suggests an active immunisation produced by the first inoculation. More data are required, however before a definite statement is made on this subject considering that individual variations, the natural capacity of reversion of the interstitial myocarditis and the employement of more than a species of Cebus monkeys probably exerts influence also in the results here reported.

Experimental investigation of transient natural convection cooling of high prandtl number fluid with variable viscosity

Report for the scientific sojourn at the James Cook University, Australia, between June to December 2007. Free convection in enclosed spaces is found widely in natural and industrial systems. It is a topic of primary interest because in many systems it provides the largest resistance to the heat transfer in comparison with other heat transfer modes. In such systems the convection is driven by a density gradient within the fluid, which, usually, is produced by a temperature difference between the fluid and surrounding walls. In the oil industry, the oil, which has High Prandtl, usually is stored and transported in large tanks at temperatures high enough to keep its viscosity and, thus the pumping requirements, to a reasonable level. A temperature difference between the fluid and the walls of the container may give rise to the unsteady buoyancy force and hence the unsteady natural convection. In the initial period of cooling the natural convection regime dominates over the conduction contribution. As the oil cools down it typically becomes more viscous and this increase of viscosity inhibits the convection. At this point the oil viscosity becomes very large and unloading of the tank becomes very difficult. For this reason it is of primary interest to be able to predict the cooling rate of the oil. The general objective of this work is to develop and validate a simulation tool able to predict the cooling rates of high Prandtl fluid considering the variable viscosity effects.

Predictors of temporary and permanent work disability in patients with inflammatory bowel disease: results of the swiss inflammatory bowel disease cohort study.

BACKGROUND: Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. METHODS: A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. RESULTS: Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. CONCLUSIONS: We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability.

Prognostication after cardiac arrest and hypothermia: a prospective study.

Current American Academy of Neurology (AAN) guidelines for outcome prediction in comatose survivors of cardiac arrest (CA) have been validated before the therapeutic hypothermia era (TH). We undertook this study to verify the prognostic value of clinical and electrophysiological variables in the TH setting. A total of 111 consecutive comatose survivors of CA treated with TH were prospectively studied over a 3-year period. Neurological examination, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) were performed immediately after TH, at normothermia and off sedation. Neurological recovery was assessed at 3 to 6 months, using Cerebral Performance Categories (CPC). Three clinical variables, assessed within 72 hours after CA, showed higher false-positive mortality predictions as compared with the AAN guidelines: incomplete brainstem reflexes recovery (4% vs 0%), myoclonus (7% vs 0%), and absent motor response to pain (24% vs 0%). Furthermore, unreactive EEG background was incompatible with good long-term neurological recovery (CPC 1-2) and strongly associated with in-hospital mortality (adjusted odds ratio for death, 15.4; 95% confidence interval, 3.3-71.9). The presence of at least 2 independent predictors out of 4 (incomplete brainstem reflexes, myoclonus, unreactive EEG, and absent cortical SSEP) accurately predicted poor long-term neurological recovery (positive predictive value = 1.00); EEG reactivity significantly improved the prognostication. Our data show that TH may modify outcome prediction after CA, implying that some clinical features should be interpreted with more caution in this setting as compared with the AAN guidelines. EEG background reactivity is useful in determining the prognosis after CA treated with TH.