and Venezuela have the domestic, peridomicile and sylvatic cycles, with high prevalence of human infection and prevalence of chronic Chagas' cardiomyopathy (CCC).Group II -Colombia, Costa Rica and Mexico, characterized by domestic and peridomicile cycles with presence of CCC.Group III -El Salvador, Guatemala, Nicaragua and Panama have domestic, peridomicile and sylvatic cycles with poor clinical information. AbstractMuch has been achieved in one century after Carlos Chagas' discovery. However, there is surely much to be done in the next decades. At present, we are witnessing many remarkable efforts to monitor the epidemiology of the disease, to better understand the biology of the T. cruzi and its interaction with human beings as well as the pathogenesis and pathophysiology of the complications in the chronic phase, and deal more appropriately and effectively with late cardiac and digestive manifestations.

Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy. In this context, antiparasitic treatment in the chronic phase of Chagas disease could prevent complications related to the disease. However, according to the results of the BENEFIT trial, benznidazole seems to have no benefit for arresting disease progression in patients with chronic Chagas cardiomyopathy. In this review, we give an update on the main pathogenic mechanisms of Chagas disease, and re-examine and discuss the results of the BENEFIT trial, together with its limitations and implications.

The relative contribution of the efferent components of the autonomic nervous system to the regulation of tachycardia induced by isometric exercise was assessed in 23 normal males. The isometric exercise (handgrip) was performed at the maximum intensity tolerated by the individual over a period of 10 s (maximal voluntary contraction-MVC) and at levels equivalent to 75, 50 and 25% of MVC for 20, 40 and 10 s, respectively. The study was performed both under control conditions and after pharmacological blockade with atropine (12 individuals) or propranolol (11 individuals). Under control conditions, the heart rate (HR) responses to isometric effort were dependent on the intensity and duration of the exercise, showing a tendency towards progressive elevation with the maintenance of muscular contraction at the levels studied. The tachycardia evoked by this effort was of considerable magnitude and of rapid onset, especially at the more intense levels of activity. Parasympathetic blockade markedly decreased tachycardia, which manifested itself during the first 10 s of exercise at all levels of intensity, whereas sympathetic blockade markedly modified the HR response after 10 s of effort at the 75 and 50% MVC levels. A slight depression of the tachycardiac response could be observed already after 10 s of maximum effort after propranolol. The present results suggest that the autonomic regulation of these responses is based on a biphasic mechanism, with the initial phase depending on the rapid withdrawal of the parasympathetic influence, followed by a marked sympathetic contribution to the induction of tachycardia after 10 s of isometric contraction or even a little before at maximum exertion.

Seven normal subjects of sedentary habits were submitted to a 10 week period of endurance physical training on a cycloergometer. The training programme produced a mean 15.6 +/- 1.4% (+/- SE) increase in VO2max (from 39.7 +/- 2.0 ml . kg-1 . min-1 to 45.9 +/- 2.4 ml . kg-1 . min-1) and a reduction in resting heart rate (HR) from 69 +/- 1.9 to 58 +/- 1.7 beats . min-1 in the supine position. After pharmacological blockade of the parasympathetic system with atropine sulphate, HR rose on average by 53 +/- 3.9 beats . min-1 before training and 47 +/- 3.6 beats . min-1 after training, the difference being statistically nonsignificant. The magnitude of respiratory sinus arrhythmia (RSA) was similar before and after the period of physical conditioning. The respiratory variation in HR ( Delta HR) at the 1 litre tidal volume was 20 +/- 2.4 beats . min-1 and 20 +/- 2.6 beats . min-1 before and after training, respectively. At the 2 litre tidal volume, these values were 25 +/- 3.2 and 27 +/- 4.5 beats . min-1. Similar results were obtained with the RSA test when a group of 13 sedentary individuals (VO2max = 39.4 +/- 1.3 ml . kg-1 . min-1) was compared with a group of 7 athletes who are medium distance runners (VO2max = 53.8 +/- 1.3 ml . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)