CLINICS 2012;67(7):821-826 Cardiac changes following overdose Faa A et al. Figure 1 - S100B positivity and cause of death. who died due to drug overdose and whether different drugs (heroin, cocaine, and polypharmacological admixtures, including ecstasy) could affect S100B protein retention in cardiomyocytes. Our preliminary data clearly show that the S100B protein is significantly more expressed in the hearts of drug users, regardless of the type of drug employed, compared with patients who died from traumatic or other pathological events. From a practical point of view, this finding suggests that S100B immunostaining could be performed in all cases of cardiac death possibly related to drug abuse to confirm the role of drug use as a cause of death. The presence of the S100B protein inside the cytoplasm of cardiomyocytes and in the interstitial spaces around cardiac cells, and the presence of myocytolysis clearly suggest cardiomyocytes as the putative main source of S100B production and release. The absence of immunoreactivity for the protein in the subepicardial fat tissue in this study is inconsistent with the previous hypothesis that cardiac adipocytes are the main source of S100B protein in the heart. Our histological data confirm the typical histological findings previously reported in cocaine-related death; i.e., contraction band necrosis (CBN), also referred to as coagulative myocytolysis, and an anomalous hypereosino- philic crossband formed by segments of hypercontracted sarcomeres with extremely thickened Z lines (43). Another interesting finding in our study is that a similar S100B protein expression pattern is observed in both cocaine and heroin abusers. One possible explanation for this finding could be the acute stress caused by both drugs on the central nervous system, followed by the induction of S100B protein overproduction in cardiomyocytes (44). Particularly strong reactivity for S100B protein was observed in some cases in which toxicological analyses suggested concomitant cocaine and heroin abuse. This finding supports the assumption that both drugs may act on the same pathways, cooperating in S100B protein overproduction, storage and release. Because both of these substances are metabolized by the same enzymes, human carboxylesterases (hCEs), we might postulate that heroin and cocaine could interfere with each other at a metabolic level when taken together, giving rise to the overproduction of S100B and leading to significant cardiac storage of the protein (45). However, to the best of our knowledge, the exact mechanism by which S100B protein is overexpressed at the cardiac level in overdose-related deaths remains unclear. The over-expres- sion of S100B protein might depend on environmental factors; it has been shown that several substances, including norepinephrine, phenylephrine, interleukin 1b (IL-1b), b- amyloid, antidepressants and pro-inflammatory cytokines, may up- or down-regulate S100B expression. Moreover, S100B expression has been attributed to catecholamines in cardiomyocytes surviving infarction (46). In fact, the S100B protein, which is undetectable in normal cardiomyocytes, is induced in the ischemic or post-infarction myocardium. These observations suggest that S100B gene expression is under complex transcriptional regulation. S100B gene expression appears to be constitutively repressed in all cell types, implying that the expression of S100B in a given cell type Figure 2 - Diffuse S100B intermyocite positivity with some positivity in perivessels spaces (arrow). Figure 3 - S100B positivity in inter-myocytes spaces with accentuation of Schwann cells in a nerve twig X 400. 823