CLINICS 2012;67(7):821-826 BASIC RESEARCH DOI:10.6061/clinics/2012(07)19 S100B protein expression in the heart of deceased individuals by overdose: a new forensic marker? Armando Faa, Giancarlo Senes, Annalisa Locci, Pietro Pampaloni, Maria Elena Pais, Bruno Piras, Ernesto d’Aloja, Gavino Faa University of Cagliari, Department of Pathology, Cagliari, Italy. OBJECTIVE: The evaluation of S100B protein expression in the human heart and its correlation with drug-related death. METHOD: Left ventricular samples were collected from 74 serial forensic autopsies (15 overdose-related deaths; 59 non-overdose-related deaths) from 2007 to 2010. Tissue sections from each sample were immunostained for S100B protein by a commercial antibody. RESULTS: The S100B protein was detected in the heart samples of all 15 cases of drug-related deaths; S100B immunoreactivity was mainly observed in the cytoplasm of cardiomyocytes and as globular deposits in the interstitial spaces. No reactivity or weak reactivity was found in the cardiomyocytes of the 59 subjects who died of other causes. CONCLUSION: Our preliminary data show that the S100B protein accumulates in injured cardiomyocytes during drug-related sudden death. Given the near absence of S100B protein in the heart of subjects who died from causes other than drug overdose, S100B immunopositivity may be used as a new ancillary screening tool for the postmortem diagnosis of overdose-related cardiac death. KEYWORDS: Chronic myocardial ischemia; Overdose, Immunohistochemistry; S100B. Faa A, Senes G, Locci A, Pampaloni P, Pais ME, Piras B, et al. S100B protein expression in the heart of deceased individuals by overdose: a new forensic marker? Clinics. 2012;67(7):821-826. Received for publication on February 19, 2012; First review completed on March 5, 2012; Accepted for publication on March 22, 2012 E-mail: armando.faa@hotmail.it Tel.: 0039-0706092370 INTRODUCTION Cocaine, a crystalline tropane alkaloid obtained from the leaves of the coca plant, is one of the most commonly used illicit drugs and acts as a powerful sympathomimetic agent, with local and systemic effects. Local effects are the consequence of the inhibition of membrane permeability to sodium during depolarization and the inhibition of the transmission of electrical impulses. Systemic effects are attributed to the inhibition of presynaptic reuptake of norepinephrine and dopamine and the secondary excess production of these neurotransmitters at receptor sites on the postganglionic neuron (1). The effects of cocaine on the cardiovascular system have been extensively documented in both animal models and humans. Cocaine administered to rats produces atrial and ventricular arrhythmias and myocardial ischemia with coronary vasoconstriction (2). High-grade ventricular Copyright 2012 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. 821 arrhythmias, myocardial infarction, and sudden cocaine- related death have been reported in humans (3). In the same study, cocaine use was shown to precipitate a cardiac event with myocardial infarct even after recreational use. Additionally, clinical evidence has shown that adverse cardiac effects are frequent during medicinal cocaine use, in which the drug is applied intranasally and intratracheally as a local anesthetic (4-6). Cocaine use has also been associated with other cardiac disorders, such as systemic hypertension, aortic aneurysms, torsades de pointes, arrhythmia, sudden coronary death (7), ischemia, ventricular tachycardia, and ventricular fibrillation (8-12). Cocaine may change cardiac rhythm by inhibiting sodium transport across membranes during depo- larization and thus inhibiting the generation and conduction of action potentials (13,14). Cocaine-related myocardial ischemia or infarction may occur immediately after cocaine use: cocaine increases the risk of acute myocardial infarct (AMI) by up to 24-fold in the first hours after use (15). The incidence of AMI is much higher in younger patients (aged 18-45 years) (16), particularly in those with other cardiac risk factors (17). The principal mechanism of cocaine-related heart damage appears to be myocardial ischemia. Three pharmacological mechanisms, likely acting in combination, are involved in the pathogenesis of cocaine-related ischemia: first, cocaine produces an increase in heart rate and blood pressure as a consequence of adrenergic stimulation; second, it causes