Cardioplexol is a crystalloid cardioplegic solution which is characterized by its reduced volume, induction of immediate cardiac arrest and prolonged duration of effect with single shot application. These aspects should simplify and speed up cardiac surgery and reduce the duration of required cross-clamping. While no experimental studies regarding Cardioplexol exist there is some clinical research, which indicates encouraging cardioprotective effects of Cardioplexol. This experimental study deals with investigating cardioprotective capacities of Cardioplexol using isolated heart perfusion in a langendorff apparatus. The aim of this study was to compare cardioprotective capacities of Cardioplexol to 45 minutes of pure ischemia, to investigate whether administration of Cardioplexol every 30 minutes can cause prolonged myocardial tolerance to ischemic conditions, and to compare cardioprotective capacities of Cardioplexol with blood based cardioplegia by Calafiore regarding 90 minutes of ischemia. Cardioprotective capacities were evaluated by measuring parameters of cardiac function, metabolism, troponin I values and electron-microscopical investigations. Comparing 45 minutes of ischemia with the use of Cardioplexol to no-flow ischemia showed only moderate cardioprotective advantages of Cardioplexol. Cardioplexol administered every 30 minutes was not able to protect myocardium sufficiently during extended periods of ischemia. During 90 minutes of ischemia Cardioplexol revealed significant inferiority compared to Calafiore. Transferring these experimental results into clinical context is challenging. Nevertheless, clinical studies have not figured out the consequences of prolonged cross-clamping on cardiac recovery after surgical interventions under Cardioplexol. Therefor the results of our study indicate that Cardioplexol does not offer sufficient cardioprotective capacities for extended cross-clamping periods. These results need to be kept in mind, when using Cardioplexol in a clinical context.