Recent innovations in stem cell technologies and the availability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have opened new possibilities for studies and drug testing on human cardiomyocytes in vitro. Still, there are concerns about the precise nature of such ‘reprogrammed’ cells. We have performed an investigation using immunocytochemistry and confocal microscopy on several cellular features using commercially available hiPSC-CMs. For some selected developmentally regulated or cardiac chamber-specific proteins, we have compared the results from hiPSC-derived cardiomyocytes with freshly isolated, ventricular cardiomyocytes from adult rats. The results show that all typical cardiac proteins are expressed in these hiPSC-CMs. Furthermore, intercalated disclike structures, calcium cycling proteins, and myofibrils are present. However, some of these proteins are only known from early developmental stages of the ventricular myocardium or the diseased adult heart. A heterogeneous expression pattern in the cell population was noted for some muscle proteins, such as for myosin light chains, or incomplete organization in sarcomeres, such as for telethonin. These observations indicate that hiPSC-CMs can be considered genuine human cardiomyocytes of an early developmental state. The here described marker proteins of maturation may become instrumental in future studies attempting the improvement of cardiomyocyte in vitro models.

Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion. S100A1 overexpressing hearts showed superior hemodynamic recover: Left ventricular pressure recovered to 57 ± 7.3% of baseline compared to 51 ± 4.6% in control (p = 0.025), this effect mirrored in LV work and dP/dt(max). Troponin T and lactate dehydrogenase was decreased in the S100A1 group, as well as FoxO pro-apoptotic transcription factor, indicating less tissue necrosis, whereas phosphocreatine content was higher after reperfusion. This is the first report of a cardioprotective effect of S100A1 overexpression in a global IRI model.

More than half of our patients recovered completely from ND due to AADA after surgery. Severity of clinical symptoms had a predictive value. Patients suffering from AADA and presenting with ND before surgery should not be excluded from emergency surgery.

Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients.