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Tissue slices from adult mammalian hearts as a model for pharmacological drug testing.

Bussek, A, Wettwer, E, Christ, T, Lohmann, H, Camelliti, P and Ravens, U (2009) Tissue slices from adult mammalian hearts as a model for pharmacological drug testing. Cell Physiol Biochem, 24 (5-6). pp. 527-536.

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AIM: Isolated papillary muscles and enzymatically dissociated myocytes of guinea-pig hearts are routinely used for experimental cardiac research. The aim of our study is to investigate adult mammalian ventricular slices as an alternative preparation. METHOD: Vibratome cut ventricular slices (350 microm thick) were examined histologically and with 2-photon microscopy for fibre orientation. Intracellular action potentials were recorded with conventional glass microelectrodes, extracellular potentials were measured with tungsten platinum electrodes and multi-electrode arrays (MEA). RESULTS: Dominant direction of fibre orientation was absent in vertical and horizontal transmural slices, but was longitudinal in tangential slices. Control action potential duration (APD(90), 169.9 +/- 4 ms) and drug effects on this parameter were similar to papillary muscles. The L-type Ca-channel blocker nifedipine shortened APD(90) with a half maximal effective concentration (EC(50)) of 4.5 microM. The I(Kr) blocker E4031 and neuroleptic drug risperidone prolonged APD(90) with EC(50) values of 31 nM and 0.67 microM, respectively. Mapping field potentials on multi-electrode arrays showed uniform spread of excitation with a mean conduction velocity of 0.47 m s(-1). CONCLUSION: Slices from adult mammalian hearts could become a useful routine model for electrophysiological and pharmacological research.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Bussek, A
Wettwer, E
Christ, T
Lohmann, H
Ravens, U
Date : 2009
DOI : 10.1159/000257528
Uncontrolled Keywords : Action Potentials, Animals, Antipsychotic Agents, Calcium Channel Blockers, Calcium Channels, L-Type, Drug Evaluation, Preclinical, Electrophysiological Phenomena, Guinea Pigs, Heart, Humans, In Vitro Techniques, Male, Microelectrodes, Nifedipine, Papillary Muscles, Rats, Rats, Wistar, Risperidone
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:00
Last Modified : 24 Jan 2020 18:14

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