Synthetic short-acting opioids are commonly used in anesthesiology as painkillers because their effect is more pronounced compared to that of natural substances. However, they have a number of side effects that, when fentanyl is used in doses larger than therapeutic, can lead to a lethal outcome. This study aimed to assess the cardiotropic effects of high doses of fentanyl using a rat heart isolated in a Langendorff perfusion system. Parameters of the heart's contractile activity were recorded with the help of PowerLab Data acquisition system 8/30 (ADInstruments, USA) and processed in the LabChartProUpgrade 7.0 program. At the concentration of 3.7 × 10^–6 M, which corresponds to the opioid content in blood after administration of a 5 ED₅₀ dose, fentanyl caused the QT interval duration to grow by 22%, as registered on an ECG, and a 256% spike of T wave (compared to control; p < 0.05). At the concentration of 7.4 × 10^–6 M (10 ED₅₀), the drug decreased heart rate by 20.4% (p < 0.05) and triggered a coronary constrictor effect that raised the perfusion pressure by 18.6% (p < 0.05). Further increase of fentanyl concentration to 1.5 × 10^–5 M (20 ED₅₀) was accompanied by an 83.5% growth of the end diastolic pressure (p < 0.05). Administration of nalmefene, nonselective opioid receptor blocker, did not cancel the cardiovasotropic action of fentanyl. Thus, fentanyl has a dose-dependent cardiotoxic effect. Despite the drop in the registered values of isolated heart's parameters, the results of this experiment confirm that cardiac activity persists under the influence of high doses of the opioid.