[Effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes].
OBJECTIVE
To investigate the effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes.


METHODS
Healthy rabbits (1.6-1.8 kg) were treated with amiodarone (80 mg x kg(-1) x d(-1)) for four weeks. Action potential duration (APD) was recorded under isolated arterially perfused left ventricular wedge preparation, then single myocytes were isolated using enzyme digestion. L-type calcium current recovery (time constant, tau) were determined by fitting data with monoexponential. Tau/APD90 were compared in cells treated with saline, amiodarone and sotalol (3 x 10(-5) mmol/L).


RESULTS
In chronic amiodarone treated myocytes, tau [(164 +/- 8) ms vs. (98 +/- 8) ms, P<0.05], APD90 [(321 +/- 12) ms vs. (220 +/- 10) ms, P<0.05] and tau/APD90 (0.51 +/- 0.03 vs. 0.44 +/- 0.03, P<0.05) were significantly increased than those in control myocytes. Sotalol significantly increased tau [(128 +/- 7) ms vs. (98 +/- 8) ms, P<0.05] and ADP90 [(405 +/- 13) ms vs. (220 +/- 10) ms, P<0.05] while reduced the tau/APD90 (0.32 +/- 0.05 vs. 0.44 +/- 0.03, P<0.05) compared to control myocytes.


CONCLUSIONS
The differential effect of amiodarone and sotalol on ventricular myocytes tau/APD90 ratio might be responsible for the safety profile of these two drugs.
Zhao
Xiao-jing
XJ
Department of Emergency, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. zxj47@yahoo.com.cn
Guo
Dong-lin
DL
Wu
Ying
Y
Liu
Teng-xian
TX
Yan
Gan-xin
GX
D000200:Action Potentials; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D013015:Sotalol; D000638:Amiodarone