HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Materials All Versions of this Article: 291/1/H269    most recent 00960.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Milan, D. J. Articles by MacRae, C. A. Search for Related Content PubMed PubMed Citation Articles by Milan, D. J. Articles by MacRae, C. A.

In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation

¹Cardiovascular Research Center and ²Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts

Submitted 8 September 2005 ; accepted in final form 12 February 2006

In the last decade the zebrafish has become a major model organism for the study of development and organogenesis. To maximize the experimental utility of this organism, it will be important to establish methods for adult phenotyping. We previously proposed that the embryonic zebrafish may be useful in high-throughput screening for drug-induced cardiotoxicity. We now describe a method for the reproducible recording of the adult zebrafish ECG and illustrate its application in the investigation of QT-prolonging drugs. Zebrafish ECGs were obtained by inserting two needle electrodes through the ventral epidermis. Fish were perfused orally, and motion artifacts were eliminated with a paralytic dose of µ-conotoxin GIIIB. Test compounds were delivered via the perfusion system. Without a means of hydration and oxygenation, the fish succumb rapidly. The use of a perfusion system allowed stable recording for >6 h. Baseline conduction intervals were as follows: PR, 66 ms (SD 14); QRS, 34 ms (SD 11); QT, 242 ms (SD 54); and R-R, 398 ms (SD 77). The known QT-prolonging agents astemizole, haloperidol, pimozide, and terfenadine caused corrected QT increases of 18% (SD 9), 16% (SD 11), 17% (SD 9), and 11% (SD 6), respectively. The control drugs clonidine, penicillin and propranolol did not prolong the corrected QT interval. In conclusion, perfusion and muscular paralysis allows stable, low-noise recording of zebrafish ECGs. Agents known to cause QT prolongation in humans caused QT prolongation in fish in each case. The development of rigorous tools for the phenotyping of adult zebrafish will complement the high-throughput assays currently under development for embryonic and larval fish.

repolarization; arrhythmia

This article has been cited by other articles:

				M. Eijgelsheim, A. L.H.J. Aarnoudse, F. Rivadeneira, J. A. Kors, J. C. M. Witteman, A. Hofman, C. M. van Duijn, A. G. Uitterlinden, and B. H.C. Stricker Identification of a common variant at the NOS1AP locus strongly associated to QT-interval duration Hum. Mol. Genet., January 15, 2009; 18(2): 347 - 357. [Abstract] [Full Text] [PDF]

				B. E. Lally, G. A. Geiger, S. Kridel, A. E. Arcury-Quandt, M. E. Robbins, N. D. Kock, K. Wheeler, P. Peddi, A. Georgakilas, G. D. Kao, et al. Identification and Biological Evaluation of a Novel and Potent Small Molecule Radiation Sensitizer via an Unbiased Screen of a Chemical Library Cancer Res., September 15, 2007; 67(18): 8791 - 8799. [Abstract] [Full Text] [PDF]

				R. Arnaout, T. Ferrer, J. Huisken, K. Spitzer, D. Y. R. Stainier, M. Tristani-Firouzi, and N. C. Chi Zebrafish model for human long QT syndrome PNAS, July 3, 2007; 104(27): 11316 - 11321. [Abstract] [Full Text] [PDF]