Aminothiol amifostine (AMI) protects against toxic effects of both ionizing radiation and numerous anticancer drugs. The aim of this study was to investigate the potential protective effects of AMI against doxorubicin (DOX)-induced cardiotoxicity in rats. Male Wistar rats were treated with AMI (75 mg/kg i.p.) and/or DOX (1.25 mg/kg i.p.), 4 times per week, for 4 weeks. Mortality, general condition and body weight of the animals were observed during the whole treatment, and for a further 4 weeks, until the end of experiment. Evaluation of cardioprotective efficacy of AMI was performed by analyzing the electrocardiographic parameters and response to the pro-arrhythmic agent aconitine, as well as activity registration of the in situ rat heart preparations. Necropsy was also performed at the end of the experiment, and heart excision, weight and macroscopic examination were done before histological evaluation. Doxorubicin caused rat heart disturbances manifested by prominent electrocardiographic changes (Salpha-T prolongation and T-wave flattening), significantly enhanced response to aconitine, decrease of the heart rate and contractility, as well as histopathologically verified myocardial lesions. The heart changes were accompanied by 40% mortality rate, significant decline in body mass and severe effusion intensity score in 66.6% of the animals. Application of AMI before each dose of DOX significantly reduced or completely prevented its toxic effects. Therefore, since AMI had very good protective effects against a high dose of DOX given as a multiple, low, unitary dose regimen, not only on the heart but on the whole rat as well, it could be recommended for further investigation in this potentially new indication for clinical application.

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Amitraz has become a signifi cant cause of acute poisoning because of its wide use in veterinary medicine during the last decade. The majority of published cases of amitraz poisoning have dealt with children, while severe life-threatening poisoning in adults is very rare. In this report, the clinical and laboratory features in a case of acute poisoning by amitraz and xylene in an adult are presented. A 72-year-old man accidentally swallowed about 40 g of Mitac 20, a commercial formulation of amitraz dissolved in xylene. The ingested dose was estimated to be about 10 g of amitraz and 35 g of xylene. Initial symptoms were dizziness and nausea, followed by coma, respiratory insuffi ciency, miosis, and hyperglycemia. As an α 2 -adrenergic agonist, amitraz usually causes bradycardia, but the present patient showed atrial fi brillation with rapid ventricular response, which was successfully treated by digoxin. Amitraz itself and xylene metabolites were confi rmed in his blood and urine, respectively, by instrumental analysis. Supportive and symptomatic measures were taken over 3 days, and the patient recovered fully despite the signifi cant ingested amounts of amitraz and xylene.

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In order to determine the frequency, severity of poisoning, and the efficacy of the applied therapeutic measures, retrospective study of 391 patients treated for acute drug poisoning was performed during one-year period at the Clinic for Emergency and Clinical Toxicology and Pharmacology. In 49 (12.5%) patients cardiovascular agents were the cause of poisoning, most frequently beta-blockers and calcium antagonists (77.5%). Poisoning with antihypertensive agents was registered in 12.2% of patients, antiarrhythmics in 8.2%, and cardiotonics in 2.1%. Beta-blockers and calcium antagonists caused severe poisoning in over 40% of cases. Predominant clinical manifestations were registered on cardiovascular system, while central nervous system effects occurred secondary to cardiotoxicity. Symptomatic and supportive measures were performed most frequently, while specific agents, glucagon, calcium salts, and others, were used less often.