title: The force of the spontaneously contracting zebrafish heart, in the assessment of cardiovascular toxicity: application on adriamycin.
abstract: The heart of the zebrafish has been used extensively to assess the cardiotoxic effect of compounds, using the frequency of heart contractions as the main index of cardiac response to drugs. In this study, the force and the frequency generated by the spontaneously contracting zebrafish heart, isolated in saline, were found to be 0.87 ± 0.05 mN and 1.54 ± 0.03 Hz (n=6) respectively within the first hour of recording. Both values of force and frequency remained constant for over 8h. The advantage of prolonged vitality in the assessment of cardiovascular toxicity was shown using the well-known anticancer drug adriamycin, which has severe cardiotoxic side effects. At 10.0 μM there was a 21.05 ± 4.42% (p=0.02, n=4) decrease in the force of contraction, while the frequency was not affected after 3h treatment (p>0.05). At 50.0 and 100.0 μM there was a 33.24 ± 3.0 and 46.6 ± 4.80% irreversible decrease in force (p<0.05, n=4), while a 18.02 ± 4.07% and 16.16 ± 4.07% reversible increase was observed in the frequency (p=0.02, n=4). These contradictory positive chronotropic and negative inotropic responses indicate the strong inhibitory effect of adriamycin on ventricular cardiomyocytes and its excitatory effects on auto-rhythmical pacemaker cells. If heart frequency was the only parameter used to assess the cardiotoxic effect of adriamycin, at the above range of concentrations, this compound would have been classified as non-cardiotoxic.
authors.affiliation: Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Triantafyllia
authors.initials: T
authors.lastname: Orfanidou
authors.forename: Chrisovalantis
authors.initials: C
authors.lastname: Papaefthimiou
authors.forename: Efthimia
authors.initials: E
authors.lastname: Antonopoulou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Leonardos
authors.forename: George
authors.initials: G
authors.lastname: Theophilidis
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009200:Myocardial Contraction; D015027:Zebrafish
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin