Isolated rat cardiomyocytes as an experimental model for studying acute cardiotoxicity of cyclosporin A.
The acute cardiotoxicity of cyclosporin A was studied in isolated cardiac myocytes from adult rats. In an initial series of 7 animals, myocytes were incubated with concentrations of cyclosporin A ranging from 1 microgram/ml to 50 micrograms/ml. Shape changes of untreated cells, cells treated with cyclosporin A and cells treated with the solvent of cyclosporin A, Tween 80/ethanol, were evaluated. After 8 hours and 16 hours, respectively, of incubation 92 +/- 4.3% and 72 +/- 8.7% of the non-treated control cells were still rod-shaped. Cyclosporin A, however, in a concentration of 5 micrograms/ml decreased the number of rod-shaped cells (79 +/- 3.2% at 8 hours and 51 +/- 3.5% at 16 hours) in comparison to the solvent (94 +/- 3.5% at 8 hours and 76 +/- 5.8% at 16 hours, P less than 0.02). This effect became more pronounced with higher concentrations of cyclosporin A. On the other hand, Tween 80/ethanol alone in higher concentrations also led to a reduced number of rod-shaped cells. In a second series of 7 animals using Tween 80/ethanol and methanol as drug vehicles, myocytes were incubated for 16 hours with 15 micrograms/ml of cyclosporin A in a calcium containing medium (1 mM) or a calcium free medium (10(-4) M ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid). The number of remaining rod-shaped cells was higher in the calcium free medium as opposed to the medium containing calcium when the cells were exposed to cyclosporin A. It is concluded that in the applied model cyclosporin A at high concentrations has an acute cardiotoxic effect which in part appears to be calcium related.
Olbrich
H G
HG
Abteilung für Kardiologie, Universität Frankfurt, F.R.G.
Dols
S
S
Ver Donck
L
L
Kober
G
G
Kaltenbach
M
M
Mutschler
E
E
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003524:Cyclosporins / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D002118:Calcium