In Vivo Recording of the Adult Zebrafish Electrocardiogram - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 68

Figure 6.7 Photograph of the
experimental setup. The ventral
surface of the adult zebrafish is
visible. There is a perfusion
needle resting in the mouth of the
fish (white arrow) and the
recording electrodes are seen in
their standard locations (red
arrows). (See the color version of
this figure in Color Plates
section.) (Figure adapted from
Milan et al., 2006.)
6.5 CONCLUSIONS
The ex aqua techniques we have described enable the rapid assessment of the adult
zebrafish electrocardiogram and overcome the challenges of hypoxia and gill motion.
The resultant zebrafish electrocardiograms are highly reproducible, with fundamental
intervals that are remarkably similar to those observed in adult humans. The stable
system we have designed allows the study of the effects of pharmacological agents
including those known human cardiotoxins. In a series of test drugs, we have found an
excellent correlation between QTeffects in human and in the zebrafish. Even less well
characterized effects on repolarization such as the shortening of the QT interval
observed with propranolol were confirmed (Sarma et al., 1988; Endresen and
Amlie, 1990).
There is tremendous variation in the basal characteristics of cardiac electro-
physiology across the vertebrate phyla with even simple heart rate ranging from 20 to
800 bpm. Interspecies differences in repolarization have been attributed to the
variable contributions of multiple ionic currents to the integrated cardiac action
potential. Data from a wide range of genetic models have established the complexity
of ion channel biology, with role not only in passive charge movements but also in
many distinctive signaling pathways (Olgin and Verheule, 2002). These findings
suggest that electrocardiographic characteristics may not correlate well with the
species' ultimate predictive utility for human physiology and pharmacology.
Limitations of the current adult model of drug-induced QT prolongation include
the lack of aqueous solubility of all medications, and the relatively slow throughput