The aim of this study was to implement the determination of cardiac markers in preclinical research at our department. For this purpose, the pathophysiological model of acute cardiotoxicity induced by high doses of isoproterenol was used. Isoproterenol hydrochloride was intraperitoneally administrated to 42 Wistar male rats at a dose of 50 mg/kg body weight. Cardiac injury was determined by assessing the concentrations of the cardiac markers (cTnI -cardiospecific troponin I and CKMB -cardiac isoenzyme creatine kinase) in the blood at predetermined time-intervals (2, 4, 6, 12, 24 and 36 h), and confirmed by ECG. Isoproterenol hydrochloride caused an elevation in the plasma concentrations of both markers. The results showed a significant difference (P < 0.01) in the concentrations of cTnI between the experimental and control groups at 2, 4, 6 and 24 h with a maximum peak between the fourth and sixth hour. However, the difference in the concentrations of CKMB between the experimental and control groups was non-significant. This experiment confirmed that cTnI is more cardiospecific than CKMB. It also revealed the possibility to use this marker in preclinical testing.

High rates of cardiovascular mortality have long been a serious problem in all European countries. Despite advancements in health care the situation is not improving fast enough. In the last decades, no new ultra-short-acting β-blockers have been registered in the European Union except for esmolol and landionol. In this study, eight newly-synthesised ultra-short-acting β-blockers were tested. These β-blockers contain an ester functional group which can be easily cleaved by plasma or cytoplasmic esterases. The substances were prepared in the Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno. Systolic blood pressure, heart rate and the interval of the QRS complex were evaluated using normotensive laboratory Wistar rats. The tested compounds were administered intravenously into the vena jugularis during general anaesthesia. The arteria carotis was exposed and cannulated to a Universal Perfusion System Basic Unit (UPSBU) of type Uniper UP-100. The universal perfusion system for isolated organs was capable of measuring and transducing actual values of blood pressure. ECG records were made using the ECG SEIVA – Praktik Veterinary. A series of substances named 2FC2a, 2FC2b, 2FC2c, 2FC2d, and another series with substances named 2FT2a, 2FT2b, 2FT2c, 2FT2d were tested at a dose of 3 mg/kg. Results were statistically compared to placebo. The best results were obtained for propyl and butyl derivatives with the highest lipophilicity. These acted as the best blood pressure reducers immediately after their administration. None of the compounds notably affected the heart rate. Statistical data show that carbamate substitution considerably prolongated the duration of the QRS complex as compared to placebo or etheric substitution. The carbamate substitution caused a pronounced arrhythmogenic effect. Thus, we could confirm the short-term hypotensive effect of the compounds. We observed an effect on the electrical conduction system of the heart while no effects were observed on heart rate. Our study contributes to better describing potential new ultra-short-acting β-blockers and facilitates selection for further testing.

No abstract