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


METHODS
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).


CONCLUSIONS
Slices from adult mammalian hearts could become a useful routine model for electrophysiological and pharmacological research.
Bussek
Alexandra
A
Department of Pharmacology and Toxicology, University of Technology, Dresden, Germany.
Wettwer
Erich
E
Christ
Torsten
T
Lohmann
Horst
H
Camelliti
Patrizia
P
Ravens
Ursula
U
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology
D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine; D018967:Risperidone