MicroRNA profiling identifies miR-7-5p and miR-26b-5p as differentially expressed in hypertensive patients with left ventricular hypertrophy.

Recent evidence suggests that cell-derived circulating miRNAs may serve as biomarkers of cardiovascular diseases. However, a few studies have investigated the potential of circulating miRNAs as biomarkers for left ventricular hypertrophy (LVH). In this study, we aimed to characterize the miRNA profiles that could distinguish hypertensive patients with LHV, hypertensive patients without LVH and control subjects, and identify potential miRNAs as biomarkers of LVH. LVH was defined by left ventricular mass indexed to body surface area >125 g/m2 in men and >110 g/m2 in women and patients were classified as hypertensive when presenting a systolic blood pressure of 140 mmHg or more, or a diastolic blood pressure of 90 mmHg or more. We employed miRNA PCR array to screen serum miRNAs profiles of patients with LVH, essential hypertension and healthy subjects. We identified 75 differentially expressed miRNAs, including 49 upregulated miRNAs and 26 downregulated miRNAs between LVH and control patients. We chose 2 miRNAs with significant differences for further testing in 59 patients. RT-PCR analysis of serum samples confirmed that miR-7-5p and miR-26b-5p were upregulated in the serum of LVH hypertensive patients compared with healthy subjects. Our findings suggest that these miRNAs may play a role in the pathogenesis of hypertensive LVH and may represent novel biomarkers for this disease.

Neuronal circuits involved in osmotic challenges.

The maintenance of plasma sodium concentration within a narrow limit is crucial to life. When it differs from normal physiological patterns, several mechanisms are activated in order to restore body fluid homeostasis. Such mechanisms may be vegetative and/or behavioral, and several regions of the central nervous system (CNS) are involved in their triggering. Some of these are responsible for sensory pathways that perceive a disturbance of the body fluid homeostasis and transmit information to other regions. These regions, in turn, initiate adequate adjustments in order to restore homeostasis. The main cardiovascular and autonomic responses to a change in plasma sodium concentration are: i) changes in arterial blood pressure and heart rate; ii) changes in sympathetic activity to the renal system in order to ensure adequate renal sodium excretion/absorption, and iii) the secretion of compounds involved in sodium ion homeostasis (ANP, Ang-II, and ADH, for example). Due to their cardiovascular effects, hypertonic saline solutions have been used to promote resuscitation in hemorrhagic patients, thereby increasing survival rates following trauma. In the present review, we expose and discuss the role of several CNS regions involved in body fluid homeostasis and the effects of acute and chronic hyperosmotic challenges.

Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats.

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280-350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50-60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats.

Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0.3 m-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98.6 (sem 2.6) v. 118.3 (sem 2.7) mmHg, P< 0.05) and HR (365.4 (sem 12.2) v. 398.2 (sem 7.5) beats per min, P< 0.05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12.1 (sem 0.6) ml and 7.8 (sem 1.1), respectively, P< 0.05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.

Infarto agudo do miocárdio e injeção intramiocárdica experimental em cães: estudos clínico, enzimático, eletrocardiográfico e ecocardiográfico / Experimental acute myocardial infarction in dogs: clinic, enzymatic, electrocardiographic and echocardiographic studies

Os eventos isquêmicos em cães são incomuns, porém podem estar sendo subnotificados. Avaliou-se o infarto agudo do miocárdio (IAM) clinicamente, por meio de eletrocardiografia (ECG), eletrocardiografia contínua (EC), ecocardiografia (ECO), enzima creatina quinase (CK), enzima creatina quinase fração MB (CK-MB) e anátomo-histologicamente em cães sem raça definida, e observou-se a ocorrência de arritmias após injeção intramiocárdia por EC. O IAM foi obtido após a ligadura da coronária descendente anterior. Os animais apresentaram ao ECO dilatação da câmara esquerda e aumento do índice de desempenho miocárdico. Ao ECG houve desnivelamento de ST nas derivações pré-cordiais V1 e V2. No EC observaram-se arritmias ventriculares graves e supradesnivelamento de ST. As enzimas CK e CK-MB aumentaram significativamente, sendo que os picos de CK-MB e de CK ocorreram seis horas e 12 horas, respectivamente, após o IAM. Na análise histológica constatou-se infarto da parede inferior do ventrículo esquerdo e substituição do tecido muscular por tecido fibroso. Avaliou-se a injeção intramiocárdica por EC que pode servir como via terapêutica cardíaca, não sendo observado aumento das arritmias ventriculares após a injeção no miocárdio infartado. O infarto em cães pode ser detectado pelos exames cardíacos disponíveis, e a injeção intramiocárdica é uma via terapêutica cardíaca possível.

Ischemic events in dogs are uncommon; however, this may be under-reported. The myocardial infarction was created by left anterior descending coronary ligation in healthy mongrel dogs in clinical and laboratorial exams. These dogs were evaluated clinically, electrocardiography (ECG), through ambulatory electrocardiography (AE), echocardiography (ECO), creatine kinase enzyme (CK), creatine kinase MB fraction enzyme (CK-MB) and histopathologically. Even in these animals we observed the occurrence of arrhythmia after intramyocardial injection by AE. The animals exhibited left ventricular chamber enlargement and increase in myocardial performance index at ECO. In ECG, there were deviations in ST segment in the precordial leads V1 and V2. CK and CK-MB showed high increase, CK and CK-MB peaks occurred six and 12 hours after infarction, respectively. Histopathology of the infarction in the inferior wall of the left ventricle and replacement of muscle tissue by fibrous tissue were seen. Furthermore, intramyocardial injection that may be used for therapeutic purposes was evaluated by AE, which demonstrated no increase in the ventricular arrhythmias. Therefore, myocardial infarction in dogs can be detected with the tests available and intramyocardial injection can be used as a therapeutic way.

Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study.

BACKGROUND: Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. METHODS: A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. RESULTS: Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 ± 13.6 years old (range 11-69); creatinine: 1.46 ± 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 ± 83.9 months (range 3-340); and time from YFV at the time of survey: 45 ± 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). CONCLUSIONS: YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life-threatening side effects may occur.

Recommendations for use of marginal donors in heart transplantation: Brazilian Association of Organs Transplantation guideline.

The high prevalence of heart failure has increased the candidate list for heart transplantation; however, there is a shortage of viable donated organs, which is responsible for the high mortality of patients awaiting a transplantation. Because the marginal donor presents additional risk factors, it is not considered to be an ideal donor. The use of a marginal donor is only justified in situations when the risk of patient death due to heart disease is greater than that offered by the donor. These recommendations sought to expand the supply of donors, consequently increasing the transplant rate. We selected articles based on robust evidence to provide a substratum to develop recommendations for donors who exceed the traditional acceptance criteria. Recipient survival in the immediate postoperative period is intimately linked to allograft quality. Primary allograft failure is responsible for 38% to 40% of immediate deaths after heart transplantation: therefore; marginal donor selection must be more rigorous to not increase the surgical risk. The main donor risk factors with the respective evidence levels are: cancer in the donor (B), female donor (B), donor death due to hemorrhagic stroke (B), donor age above 50 years (relative risk [RR] = 1.5) (B), weight mismatch between donor and recipient < 0.8 (RR = 1.3) (B), ischemia > 240 minutes (RR = 1.2) (B), left ventricular dysfunction with ejection fraction below 45% (B), and use of high doses of vasoactive drugs (dopamine > 15 mg/kg·min) (B). Factors that impact recipient mortality are: age over 50 years (RR = 1.5); allograft harvest at a distance; adult recipient weighing more than 20% of the donor; high doses of vasoactive drugs (dopamine greater than 15 mg/kg·min) and ischemic time >4 hours. The use of a marginal donor is only justified when it is able to increase life expectancy compared with clinical treatment, albeit the outcomes are interior to those using an ideal donor.

[Mutation of the aprataxin gene presenting with Charcot-Marie-Tooth-like neuropathy and cerebellar ataxia]. / Amyotrophie de type Charcot-Marie-Tooth associée à une ataxie cérébelleuse autosomique récessive révélatrice d'une mutation du gène de l'aprataxine.

BACKGROUND: Phenotype-genotype correlations, generally based on predominant associated signs, are being increasingly used to distinguish different types of autosomal recessive cerebellar ataxias (ARCA). CASE REPORTS: Two brothers developed signs of cerebellar ataxia with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. The examination also showed oculomotor apraxia. Sural nerve biopsy revealed conspicuous reduction in the density of myelinated fibres but preservation of unmyelinated nerve fibres. Blood tests revealed low serum albumin and elevated cholesterol. A homozygous W279X truncating mutation was identified in exon 6 of the APTX gene, confirming the diagnosis of cerebellar ataxia with oculomotor apraxia type 1 (AOA1). CONCLUSIONS: These cases illustrate the presentation of AOA1 type of ARCA and discuss the role of peripheral neuropathy in the differential diagnostic of the ARCAs variants.

Aprataxin gene mutations in Tunisian families.

The authors report clinical and genetic study of 13 patients from three unrelated Tunisian families with an early onset cerebellar ataxia associated with oculomotor apraxia. Cerebellar ataxia with oculomotor apraxia 1 (AOA1) represents a clinically heterogeneous disease caused by mutations in the aprataxin gene. Two novel mutations were identified, the complete deletion of the gene, which seems to not correlate with an increased severity of the disease, and a splice mutation on the acceptor splice site of exon 7.

Thermoregulation in hypertensive men exercising in the heat with water ingestion.

Hydration is recommended in order to decrease the overload on the cardiovascular system when healthy individuals exercise, mainly in the heat. To date, no criteria have been established for hydration for hypertensive (HY) individuals during exercise in a hot environment. Eight male HY volunteers without another medical problem and 8 normal (NO) subjects (46 +/- 3 and 48 +/- 1 years; 78.8 +/- 2.5 and 79.5 +/- 2.8 kg; 171 +/- 2 and 167 +/- 1 cm; body mass index=26.8 +/- 0.7 and 28.5 +/- 0.6 kg/m2; resting systolic (SBP)=142.5 and 112.5 mmHg and diastolic blood pressure (DBP)=97.5 and 78.1 mmHg, respectively) exercised for 60 min on a cycle ergometer (40% of VO2peak) with (500 ml 2 h before and 115 ml every 15 min throughout exercise) or without water ingestion, in a hot humid environment (30 masculine C and 85% humidity). Rectal (Tre) and skin (Tsk) temperatures, heart rate (HR), SBP, DBP, double product (DP), urinary volume (Vu), urine specific gravity (Gu), plasma osmolality (Posm), sweat rate (S R), and hydration level were measured. Data were analyzed using ANOVA in a split plot design, followed by the Newman-Keuls test. There were no differences in Vu, Posm, Gu and S R responses between HY and NO during heat exercise with or without water ingestion but there was a gradual increase in HR (59 and 51%), SBP (18 and 28%), DP (80 and 95%), Tre (1.4 and 1.3%), and Tsk (6 and 3%) in HY and NO, respectively. HY had higher HR (10%), SBP (21%), DBP (20%), DP (34%), and Tsk (1%) than NO during both experimental situations. The exercise-related differences in SBP, DP and Tsk between HY and NO were increased by water ingestion (P<0.05). The results showed that cardiac work and Tsk during exercise were higher in HY than in NO and the difference between the two groups increased even further with water ingestion. It was concluded that hydration protocol recommended for NO during exercise could induce an abnormal cardiac and thermoregulatory responses for HY individuals without drug therapy.

Thermoregulation in hypertensive men exercising in the heat with water ingestion

Hydration is recommended in order to decrease the overload on the cardiovascular system when healthy individuals exercise, mainly in the heat. To date, no criteria have been established for hydration for hypertensive (HY) individuals during exercise in a hot environment. Eight male HY volunteers without another medical problem and 8 normal (NO) subjects (46 ± 3 and 48 ± 1 years; 78.8 ± 2.5 and 79.5 ± 2.8 kg; 171 ± 2 and 167 ± 1 cm; body mass index = 26.8 ± 0.7 and 28.5 ± 0.6 kg/m²; resting systolic (SBP) = 142.5 and 112.5 mmHg and diastolic blood pressure (DBP) = 97.5 and 78.1 mmHg, respectively) exercised for 60 min on a cycle ergometer (40 percent of VO2peak) with (500 ml 2 h before and 115 ml every 15 min throughout exercise) or without water ingestion, in a hot humid environment (30ºC and 85 percent humidity). Rectal (Tre) and skin (Tsk) temperatures, heart rate (HR), SBP, DBP, double product (DP), urinary volume (Vu), urine specific gravity (Gu), plasma osmolality (Posm), sweat rate (S R), and hydration level were measured. Data were analyzed using ANOVA in a split plot design, followed by the Newman-Keuls test. There were no differences in Vu, Posm, Gu and S R responses between HY and NO during heat exercise with or without water ingestion but there was a gradual increase in HR (59 and 51 percent), SBP (18 and 28 percent), DP (80 and 95 percent), Tre (1.4 and 1.3 percent), and Tsk (6 and 3 percent) in HY and NO, respectively. HY had higher HR (10 percent), SBP (21 percent), DBP (20 percent), DP (34 percent), and Tsk (1 percent) than NO during both experimental situations. The exercise-related differences in SBP, DP and Tsk between HY and NO were increased by water ingestion (P < 0.05). The results showed that cardiac work and Tsk during exercise were higher in HY than in NO and the difference between the two groups increased even further with water ingestion. It was concluded that hydration protocol recommended for NO during exercise could induce an abnormal cardiac and thermoregulatory responses for HY individuals without drug therapy.

Phenotypic variability of aprataxin gene mutations.

The clinical and genetic features of three non-Portuguese and non-Japanese patients with aprataxin gene mutations are reported. Patient 1 came from Italy and presented with typical ataxia with ocular motor apraxia (OMA). She was homozygous for the W279X nonsense mutation, which is associated with the Portuguese founding haplotype. Patients 2 and 3 were French siblings and did not present with either OMA or hypoalbuminemia. They were compound heterozygous for the nonsense W279X mutation and a missense K197Q mutation.

Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus.

BACKGROUND: Ten neurodegenerative disorders characterized by spinocerebellar ataxia (SCA) are known to be caused by trinucleotide repeat (TNR) expansions. However, in some instances the molecular diagnosis is considered indeterminate because of the overlap between normal and affected allele ranges. In addition, the mechanism that generates expanded alleles is not completely understood. OBJECTIVE: To examine the clinical and molecular characteristics of a large group of Portuguese and Brazilian families with ataxia to improve knowledge of the molecular diagnosis of SCA. PATIENTS AND METHODS: We have (1) assessed repeat sizes at all known TNR loci implicated in SCA; (2) determined frequency distributions of normal alleles and expansions; and (3) looked at genotype-phenotype correlations in 202 unrelated Portuguese and Brazilian patients with SCA. Molecular analysis of TNR expansions was performed using polymerase chain reaction amplification. RESULTS: Patients from 110 unrelated families with SCA showed TNR expansions at 1 of the loci studied. Dominantly transmitted cases had (CAG)(n) expansions at the Machado-Joseph disease gene (MJD1) (63%), at SCA2 (3%), the gene for dentatorubropallidoluysian atrophy (DRPLA) (2%), SCA6 (1%), or SCA7 (1%) loci, or (CTG)(n) expansions at the SCA8 (2%) gene, whereas (GAA)(n) expansions in the Freidreich ataxia gene (FRDA) were found in 64% of families with recessive ataxia. Isolated patients also had TNR expansions at the MJD1 (6%), SCA8 (6%), or FRDA (8%) genes; in addition, an expanded allele at the TATA-binding protein gene (TBP), with 43 CAGs, was present in a patient with ataxia and mental deterioration. Associations between frequencies of SCA2 and SCA6 and a frequency of large normal alleles were found in Portuguese and Brazilian individuals, respectively. Interestingly, no association between the frequencies of DRPLA and large normal alleles was found in the Portuguese group. CONCLUSIONS: Our results show that (1) a significant number of isolated cases of ataxia are due to TNR expansions; (2) expanded DRPLA alleles in Portuguese families may have evolved from an ancestral haplotype; and (3) small (CAG)(n) expansions at the TBP gene may cause SCA17.

The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.

The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.

Immunological and clinical evaluation of chagasic patients subjected to chemotherapy during the acute phase of Trypanosoma cruzi infection 14-30 years ago.

We recently evaluated the in vitro proliferative response and interferon (IFN)-gamma production of peripheral blood mononuclear cells from a group of 25 people who were treated for Chagas' disease during the acute phase of Trypanosoma cruzi infection and followed up for a period of 14-30 years. On the basis of the parasitological and serological tests, the individuals were classified as cured (C), dissociated, or not cured (NC). Members of group C (the group without cardiac alterations) presented significantly stronger proliferative response against the parasite antigens, with secretion of high levels of IFN-gamma in comparison with the NC group, raising a question about the role of this cytokine in the curing of human T. cruzi infection. Severe cardiac alterations were observed only in 1 of 25 patients, which suggests that treatment benefited the patients.

Genetic characterization of Trypanosoma cruzi directly from tissues of patients with chronic Chagas disease: differential distribution of genetic types into diverse organs.

We have previously shown that a low-stringency single-specific primer-polymerase chain reaction (LSSP- PCR) is a highly sensitive and reproducible technique for the genetic profiling of Trypanosoma cruzi parasites directly in tissues from infected animals and humans. By applying LSSP-PCR to the study of the variable region of kinetoplast minicircle from T. cruzi, the intraspecific polymorphism of the kinetoplast-deoxyribonucleic acid (kDNA) sequence can be translated into individual kDNA signatures. In the present article, we report on our success using the LSSP-PCR technique in profiling the T. cruzi parasites present in the hearts of 13 patients with chagasic cardiopathy and in the esophagi of four patients (three of them with chagasic megaesophagus). In two patients, one with the cardiodigestive clinical form of Chagas disease and the other with cardiopathy and an esophageal inflammatory process, we could study both heart and esophagus and we detected distinct kDNA signatures in the two organs. This provides evidence of a differential tissue distribution of genetically diverse T. cruzi populations in chronic Chagas disease, suggesting that the genetic variability of the parasite is one of the determining factors of the clinical form of the disease.

Cardiac autonomic denervation in congestive heart failure: comparison of Chagas' heart disease with other dilated cardiomyopathy.

Congestive heart failure (CHF) is associated with activation of the cardiac sympathetic nerves. However, impairment of the sympathetic nerve terminals in patients with CHF has been indicated by studies showing reduction of cardiac norepinephrine uptake and stores. This investigation studies the histochemical evaluation of the sympathetic nerve terminals in CHF. The cardiac parasympathetic innervation was also studied to address the question of specificity of the presumed sympathetic denervation. Nineteen patients with CHF underwent cardiac transplantation or partial ventriculectomy, which provided the heart tissue. In 11 of them, the dilated cardiomyopathy was associated with Chagas' disease. Inflammatory process and fibrosis were studied histologically. The sympathetic and parasympathetic nerve fibers were visualized through histochemical techniques for, respectively, catecholamines and acetylcholinesterase activity. By using a computer-assisted morphometric program, the inflammation, fibrosis, and parasympathetic innervation were quantified. Moderate to severe fibrosing myocarditis characterized the hearts of the chagasic patients. In cardiomyopathies not associated with Chagas' disease, the inflammation was discrete, if present, but the amount of fibrosis was similar to that found in Chagas' cardiomyopathy. Reduction of both kinds of nerve terminals occurred in the heart of all patients. The parasympathetic denervation was proven to be more severe in chagasic cardiomyopathy. Our data on the heart innervation indicate a progressive autonomic denervation in heart failure. In Chagas' heart disease, the denervation seems to be more severe or rapid, probably because of the sustained inflammatory process.