)]. chronic complete atrioventricular block and acquired torsades de pointes. Drug-induced and genetic animal models of various species have been generated and have been instrumental for identifying pro-arrhythmic triggers and important characteristics of the arrhythmogenic substrate in LQTS. But soon after Eduardo Kac’s images of Alba, a transgenic bunny, appeared in 2000 the world took notice. This is a protein used in many standard biological experiments involving fluorescence. Farkas, A. S., Acsai, K., Toth, A., Dezsi, L., Orosz, S., Forster, T., et al. Atrial and ventricular refractoriness and AP duration were shortened in SQT1 (vAPD90, 118.6 ± 5 ms vs. 154.4 ± 2, P < 0.0001). Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. There is a gulf in understanding between the common person and the scientist; indeed, in many cases this gulf is increasing exponentially as scientists' fields become ever more specialized and narrow in focus. Ziv, O., Morales, E., Song, Y. K., Peng, X., Odening, K. E., Buxton, A. E., et al. Blenck, C. L., Harvey, P. A., Reckelhoff, J. F., and Leinwand, L. A. Dealing with, global safety issues : was the response to QT-liability of non-cardiac drugs well. This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration–sponsored Think Tank Meeting on May 22, 2018. Scientists in the genetic engineering field, however, object to the project as frivolous, saying that there are things of greater import that could be done with the fluorescence genes.2 Transgenic art is a term Kac has coined as "a new art form based on the use of genetic engineering techniques to transfer synthetic genes to an organism or to transfer natural genetic material from one species into another, to create unique living beings. Lengyel, C., Virag, L., Kovacs, P. P., Kristof, A., Pacher, P., Kocsis, E., et al. Inaba, H., Hayami, N., Ajiki, K., Kunishima, T., Watanabe, H., Tsutsui, K., et al. Food, and Drug Administration, H.H.S (2005a). Genetically modified laboratory animals provide a powerful approach for studying gene expression and regulation and allow one to directly examine structure-function and cause-and-effect relationships in …

(B) Representative ECG tracings indicating differences in QT interval in WT, LQT1, LQT2, and LQT5 rabbits [ECG from WT, LQT1 and LQT2 modified from (Brunner et al., 2008)]. Deep anesthesia suppresses ventricular tachyarrhythmias in rabbit, Jacobson, I., Carlsson, L., and Duker, G. (2011). Cardiac arrest secondary to long QT(C) in a. Jost, N., Virag, L., Bitay, M., Takacs, J., Lengyel, C., Biliczki, P., et al. Assessment of the. (2010). Husti, Z., Tabori, K., Juhasz, V., Hornyik, T., Varro, A., and Baczko, I. dofetilide to induce torsade de pointes in rabbit hearts.

Eduardo Kac has come to Paris to get his bunny back. polymorphic ventricular tachycardia with normal QT interval. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased-partially reversing the phenotype-while a small increase in IKs may partly contribute to an accentuation of the phenotype. (2008). The general public could be forgiven for being suspicious, then, of "miracle" fixes offered by these scientific shamans. Volders, P. G., Sipido, K. R., Vos, M. A., Spatjens, R. L., Leunissen, J. D., Carmeliet, E., et al. Age- and sex-related differenc. (2000).

(2005). Kaese, S., and Verheule, S. (2012). Haverkamp, W., Breithardt, G., Camm, A. J., Janse, M. J., Rosen, M. R., Antzelevitch, C., et al. Modi, blocker D-sotalol in dogs with acute (left panel) and chronic AV-block (right panel). In transgenic LQTS. Lehmann, M. H., Hardy, S., Archibald, D., Quart, B., and Macneil, D. J. The dashed line represents the mean QT indexes in free-moving rabbits, heterogeneous prolongation of cardiac repolarization caused by, various groups of drugs blocking multiple ion channels. Therefore, current safety screening in, industry rely on combined use of pre-clinical, of HERG function, action potential (AP) and, (IRA) approach], and clinical ECG studies, Instability of Repolarization (Used in In Vivo and In Vitro, approach led to elimination of potentially promising drug, channel effects, and 3) evaluation of the drug effect on, integrated biological systems such as on stem-cell-derived, in order to better predict the drug effect on AP shape and, derives from the huge inter-individual differences in, susceptibility to arrhythmia, which makes the overall risk, ability of cardiomyocytes to maintain suf, despite repolarization-prolonging (mostly K, the most important role in decreasing repolarization reserve, healthy animals with intact repolarization or on their tissues/, with increased sensitivity to channel blockers other than only, , and (ii) representing different degrees, suggested to employ in proarrhythmia research (, repolarization reserve capacity and therefore affect susceptibility to, arrhythmia. (2006). Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs. Eduardo Kac's GFP Bunny, a Work of Transgenic Art, or, It's Not Easy Being Green Kim Slawson Herewith is presented Eduardo Kac's transgenic art work, GFP Bunny. on potential future directions and novel models.

All rights reserved. Blinded test in isolated female rabbit. (A) Upper panel (i): Bar graphs of action potential durations (APD) and dispersion of APD (DAPD) in Langendorff-perfused hearts of WT, LQT1, and LQT2 rabbits indicate longer APD and increased APD dispersion in LQT2 hearts, *p < 0.05 [modified from (Brunner et al., 2008)]. Computer simulations showed that APD prolongation and slowed heart rates caused early afterdepolarization-mediated APD alternans and chaos, manifesting as TWA and TWL, respectively. Strasberg, B., Welch, W., Palileo, E., Swiryn, S., Bauernfeind, R., and Rosen, K. M. (1983).

Superovulation was induced, in wild-type (WT) rabbits using hormonal stimulation with FSH, and GnRH-analogues, and inseminated oocytes were, microinjected with transgenic mutant DNA-constructs and re-, female WT rabbits resulted in vertical transmission with 50%, transgenic and 50% WT offspring. Paltoo, B., O'donoghue, S., and Mousavi, M. S. (2001). sotalol.

Kurokawa, J., Tamagawa, M., Harada, N., Honda, S., Bai, C. X., Nakaya, H., et al. In the end, we give an outlook. Tpeak - Tend and, Tpeak - Tend /QT ratio as markers of ventricular arrhythmia risk in cardiac. Black line indicates changes in voltage fluorescence signal (Vm); red line indicates changes in Ca 2+ signal [modified from (Odening et al., 2012b)]. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs. Retrieved November 7, 2000 from the World Wide Web: http://abcnews.go.com/sections/science/DailyNews/rabbit000918.html 3 Kac, Eduardo. These studies suggest that progesterone-, ), thus rendering patients at increased risk. Dutta, S., Minchole, A., Zacur, E., Quinn, T. A., Taggart, P., and Rodriguez, B. (2003). One frequently used drug-induced model is the methoxamine-, sensitized rabbit model: anesthetized rabbits are sensitized with, makes them particularly prone to develop drug-induced, indicating the importance of the degree of ion channel, anti-arrhythmic properties of various different drugs have been, arrhythmic potential for drug-induced TdP using this model, arrhythmic potential of drugs that concomitantly block, Other frequently employed drug-induced rabbit models are, representing LQT2 characteristics. Women are at higher risk for drug-induced, repolarization reserve and favors drug-induced arrhy, models (or animal models with altered hormonal state) might be, particularly sensitive in detecting potential ion channel-blocking, employed proarrhythmia markers, the importance of the choice, of species for proarrhythmia research, and the advantages and, followed by a detailed description of novel transg, rabbit models. Wolbrette, D. L. (2003). Lower panel: IV-curves of I Ks in absence and presence of 5 µM forskolin in WT or transgenic LQT5 rabbit ventricular myocytes. Many people have traditionally viewed art and science as separate, even diametrically opposite disciplines. Bar graphs show changes in QTc, STV QT , and T peak -T end in anaesthetized animals after i.m. Therefore, there is an unmet need for (i) improved, with better predictive value for pro-arrhythmic drug, A number of different electrophysiological parameters have, been investigated as non-invasive prognostic markers for TdP, and SCD risk evaluation both in animal experiments and in the, clinical setting.

Indeed, the extent of QT prolongation did not predict, cation of patients at elevated risk for drug-induced, ). (2016). The Transgenic Bunny is one of the transgenic artworks done by Eduardo Kac in collaboration with scientists Patrick Prunet, Louis-Marie Houdebine, and artist Louis Bec at the National Institute of Agronomic Research in France during the year 2000.

Sotalol testing, unmasks altered repolarization in patients with suspected acquired long-QT-.

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