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

Milan, D.J., Jones, I.L., Ellinor, P.T., and MacRae, C.A.
American journal of physiology. Heart and circulatory physiology   291(1): H269-H273 (Journal)
Registered Authors
Ellinor, Patrick, MacRae, Calum A., Milan, David J.
repolarization, arrhythmia
MeSH Terms
  • Aging
  • Animals
  • Disease Models, Animal*
  • Electrocardiography/methods*
  • Female
  • Long QT Syndrome/chemically induced
  • Long QT Syndrome/diagnosis*
  • Long QT Syndrome/physiopathology*
  • Male
  • Species Specificity
  • Zebrafish/physiology*
16489111 Full text @ Am. J. Physiol. Heart Circ. Physiol.
Background In the last decade the zebrafish has become a major model organism for the study of development and organogenesis. In order 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 electrocardiogram (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 micro-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 greater than 6 hours. Baseline conduction intervals were: PR 66+/-14, QRS 34+/-11, QT 242+/-54, and RR 398+/-77 ms. The known QT-prolonging agents astemizole, haloperidol, pimozide and terfenadine caused corrected QT increases of 23+/-14, 36+/-15, 21+/-12 and 22+/-5 percent, respectively. The control drugs clonidine, penicillin and propranolol had no significant effect on corrected QT interval. 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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes