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Thienopyridines are frequently used drugs in the management of ischemic heart diseases or thrombotic events due to its antiplatelet as well as thrombolytic properties. Recently it was shown, that these compounds exert a negative inotropic effect in the isolated guinea pig heart. Using voltage clamp technique we could demonstrate a L-type calcium current impairment possibly underlying these effects. The aim of the study is to further elucidate the effects of thienopyridines on tissue level using high resolution optical mapping in guinea pig papillary. Our experimental setup features a 16 by 16 photodiode array with individual 256 custom-built current-to-voltage amplifiers. A frequency doubled continuous wave Neodymium-Yag laser (532 nm, 2 W) is used as excitation source. The tissue is stained by incubation with the voltage sensitive dye di-4-ANEPPS. The use of different objective-magnifications (10x, 20x, 40x, 63x) allows a multi-scale based analysis with resolutions up to 15 micrometers. The setup provides a detailed view on excitation propagation. In addition, the application of external electric field pulses during the depolarization phase of the tissue sample reveals local inhomogeneities in the membrane-potential distribution at the tissue surface (and possibly 2-3 cell layers below the surface).[1] This allows us to quantify the electrical inhomogeneity of the preparation. Experiments demonstrate the importance of optical membrane potential measurements, which provide new information unattainable with other methods.[1] Windisch, H. et al. (2007): Quantification of shock-induced microscopic virtual electrodes assessed by subcellular resolution optical potential mapping in guinea pig papillary muscle. J Cardiovasc Electrophysiol 18(10), 1086-1094

Inhomogeneities in the tissue are a determining factor for cardiac function and can be either structural or functional. Using the voltage sensitive fluorescent dye di-4-ANEPPS on incubation stained guinea pig preparations allows to map the tissue's response to externally applied electric shocks. Previous work on ventricular muscle preparations revealed a membrane potential morphology that could be relevant during defibrillation [1]. Using a two pulse stimulus protocol we are able to map the excitation response to a short triggering field pulse and to consequently map the membrane potential morphology resulting from a second field pulse, which is applied in the depolarized state and is attributed to the interaction of the electric field with the tissue. This approach is now carried over to atrial preparations. A custom developed object-positioning and image-stitching method allows for wide view analysis of the atrial tissue structure. Objective-magnifications of 10x, 20x, 40x and 63x enable a multi-scale based analysis with resolutions up to 15 micrometers. This is augmented with information from transmitted light microscopy so that it is possible to correlate the membrane potential patterns with the visible structure of the atrial tissue, providing further insight into atrial excitation and conduction.[1] Windisch,H. et al. (2007) Quantification of shock-induced microscopic virtual electrodes assessed by subcellular resolution optical potential mapping in guinea pig papillary muscle. J Cardiovasc Electrophysiol; 18(10):1086-1094