SummaryBackground Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest antiischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT).

OBJECTIVES The objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.BACKGROUND Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symp-

Background: Extracellular recordings of electrical activity with substrate-integrated microelectrode arrays (MEAs) enable non-invasive long-term monitoring of contracting multicellular cardiac preparations. However, to characterize not only the spread of excitation and the conduction velocity from field potential (FP) recordings, a more rigorous analysis of FPs is necessary. Therefore in this study we aim to characterize intrinsic action potential (AP) parameters by simultaneous recording of APs and FPs. Methods: A MEA consisting of 60 substrate-integrated electrodes is used to record the FP-waveform from multicellular preparations of isolated embryonic mouse cardiomyocytes. Simultaneous current clamp recordings in the vicinity of individual microelectrodes and pharmacological interventions allowed us to correlate FP and AP components and their time course. Results: The experiments revealed a linear relationship between AP rise time and FP rise time as well as a linear relationship between AP duration and FP duration. Furthermore a direct contribution of the voltage dependent Na⁺- and Ca²⁺-current to the FP could be identified. Conclusion: The characterization of the FP allows us for the first time to estimate AP changes and the contribution of individual current components to the AP by the help of non-invasive recording within a multicellular cardiac preparation during long-term culture.

Embryonic stem cells differentiate into cardiac myocytes, repeating in vitro the structural and molecular changes associated with cardiac development. Currently, it is not clear whether the electrophysiological properties of the multicellular cardiac structure follow cardiac maturation as well. In long-term recordings of extracellular field potentials with microelectrode arrays consisting of 60 substrate-integrated electrodes, we examined the electrophysiological properties during the ongoing differentiation process. The beating frequency of the growing preparations increased from 1 to 5 Hz concomitant to a decrease of the action potential duration and action potential rise time. A developmental increase of the conduction velocity could be attributed to an increased expression of connexin43 gap junction channels. Whereas isoprenalin elicited a positive chronotropic response from the first day of spontaneous beating onward, a concentration-dependent negative chronotropic effect of carbachol only developed after approximately 4 days. The in vitro development of the three-dimensional cardiac preparation thus closely follows the development described for the mouse embryonic heart, making it an ideal model to monitor the differentiation of electrical activity in embryonic cardiomyocytes.

Abstract-In the present study, we investigated the electrophysiological maturation and integration of immature cardiomyocytes after transplantation; maturation and integration are essential to achieve the cardiac regeneration. Murine fetal cardiomyocytes (FCMs) (d12.5-d15.5) expressing enhanced green fluorescent protein under the control of the ␣-actin promoter were injected into cryoinjured areas and adjacent myocardium of cryoinjured mouse ventricles. Viable short axis tissue slices (thickness, 150 m) of the ventricles were prepared 5 to 6 days after transplantation. Glass microelectrodes were used for measurements of action potentials in transplanted FCMs and host cardiomyocytes within the slices. Stimulation at frequencies of up to 10 Hz was performed via a unipolar electrode placed in viable host tissue. Transplanted FCMs could be distinguished clearly from host tissue by their green fluorescence and their electrophysiological properties: maximal upstroke velocity (V max ) was significantly lower and action potential duration at 50% repolarization (APD 50 ) was significantly longer compared with values of adult cardiomyocytes. Transplanted FCMs surrounded by cryoinjured tissue showed spontaneous electrical and contractile activity, which was in no case synchronous with host tissue. V max and APD 50 of these nonintegrated cells matched values of cultivated dissociated FCMs. In contrast, 82% of transplanted FCMs surrounded by viable host tissue were electrically integrated; ie, electrical and contractile activity was synchronous with host tissue and these cells had more mature action potential parameters (significantly higher V max and shorter APD 50 ) compared with nonintegrated FCMs. In conclusion, electrophysiological maturation and integration of transplanted FCMs depend on an embedment in viable host myocardium. Key Words: cardiac electrophysiology Ⅲ cardiomyoplasty Ⅲ coupling Ⅲ heart slices Ⅲ maturation A cute myocardial infarction and chronic heart failure are among the most frequent causes of morbidity and mortality in Western countries. In the course of physiological reparation processes, cardiomyocytes lost because of myocardial infarction are replaced by scar tissue, leading to an impaired cardiac function and remodeling of the remaining myocardium. Despite advances in the conventional therapy, this loss of functional myocardium remains irreversible. Thus, there is a strong need for a novel therapeutic approach aiming at a regeneration of cardiomyocytes: cardiac cell therapy.Cardiomyocytes derived from embryonic stem cells (ESCCMs) are promising candidates for cell therapy via an exogenic replacement of lost cardiomyocytes, because their cardiac phenotype, including cardiac specific protein expression as well as typical cardiac electrophysiological properties, is undoubted. 1 Clinical studies using ESC-CMs have not been performed, because, first, techniques enabling the production and selection of sufficient cell numbers must be developed and potential risks and immunological issues must be investi...