**5. Pathology**

132 Myocarditis

CCC patients with heart failure had more neuronal depletion than patients with dilated cardiomyopathy of other causes (Oliveira J. S., 1985). In our experience the neuroganglionic

According to pioneer neurogenic hypothesis (Köberle, 1959), early and irreversible damage to the parasympathetic system during acute phase of the disease causes a cathecolaminergic cardiomyopathy, but this point of view has been debated and evidence is contradictory. Functional test performed in CCC patients demonstrated impaired parasympathetic heart rate regulation (metaraminol, phenylephrine and atropine intravenous injections, facial immersion, Valsalva maneuver, head-up and head-down tilt tests, respiratory sinus arrhythmia, handgrip, graded dynamic exercise, and spectral analysis of Holter recordings) (Amorim, et al., 1968, Amorim, et al., 1973, Gallo, et al., 1975, Guzzetti, et al., 1991, Junqueira Junior, et al., 1985, Manço, et al., 1969, Marin-Neto, et al., 1975, Sousa, et al., 1987). However, a careful analysis of these data showed that many patients had normal autonomic function and most patients had heart failure, that could explain autonomic dysfunction *per se* (Davila,

On the other hand, the study of indeterminate patients has shown conflicting results. While some authors could demonstrate impaired autonomic function (Molina, et al., 2006, Vasconcelos & Junqueira, 2009) others could demonstrate that autonomic function was normal in patients without myocardial damage and that abnormalities in autonomic dysfunction was proportional to heart dysfunction, leading these authors to propose that these abnormalities arise as a compensating mechanism for the progressive left ventricular dilatation (Davila, et al., 1991, Davila Spinetti, et al., 1999). These findings led to a new "neurogenic theory", which considers autonomic dysfunction as secondary to ventricular dilatation and hemodynamic alterations, but once installed, acts synergistically with parasitism and inflammation to cause further myocardial damage (Davila, et al., 2004).

Microcirculation abnormalities in CCC have been firstly pointed out by Jorg as an angiographic anarchy due to capillary loss (Jörg, 1974) and furtherly demonstrated in

Many investigators have found abnormal myocardial perfusion using isonitrile-99mtechnetium (Castro R., et al., 1988) and thallium-201 (Hagar & Rahimtoola, 1991, Marin-Neto, et al., 1992) scintigraphy in chagasic patients with normal epicardial coronary arteries. Furthermore, the progression of left ventricular systolic dysfunction is associated with both, the presence of reversible perfusion defects and the increase in perfusion defects at rest (Hiss, et al., 2009, Schwartz & Wexler, 2009). Anatomopathological studies in humans also provided evidence of microvascular damage in CCC. In late 1950's first reports showing collapse of arterioles and intimal proliferation (Torres, 1960) caught the attention of investigators. Also, microthrombi have been described (Rossi M. A., et al., 1984). As said, in endomyocardial biopsies thickening of capillary basement membranes was also found

Additional evidence of microvascular damage was obtained from experimental models. Vascular constriction, microaneurysms, dilatation and proliferation of microvessels has been demonstrated (Factor & Sonnenblick, 1982, Morris, et al., 1989, Tanowitz H. B., et al.,

Many factors have been advocated in the genesis of these lesions. First, the parasite itself. It was shown that *T. cruzi* produces a neuraminidase that removes sialic acid from de surface

experimental models as well as in clinical practice (Rossi M. A., et al., 2010).

involvement was variable in autopsies of chagasic hearts (Milei, et al., 1991b).

et al., 1998).

**4.2 Microvascular damage** 

(Milei, et al., 1992b).

1996, Tanowitz Herbert B., et al., 1992b).

Pathological findings are described mostly according to our own findings.
