[Clinical and experimental study of cardiac effects of conventional dosage arsenic trioxide in APL patients].
OBJECTIVE
To investigate cardiac effects of arsenic trioxide (As(2)O(3)) at conventional dosage in acute promyelocytic leukemia (APL) patients.


METHODS
The basical heart rate, electrocardiograph, plasma As(2)O(3) concentration of APL patients were dynamically monitored. The action potential duration and current of I(Ca-L) in guinea pig cardiac ventricular myocytes were assayed by patch clamp technique, and the elevated cytosolic [Ca(2+)]i of guinea pig ventricular myocytes induced by As(2)O(3) by laser confocal microscopy.


RESULTS
Approximately 52.5% - 35% of 40 APL patients manifested poor cardiac effects of different degree when As(2)O(3) intravenous infused at conventional doses in the initial 1 or 2 weeks with fast heart rate or prolonged QT interval. As(2)O(3) at concentration of 1, 2, 5 micro mol/L prolonged action potential duration from (563.0 +/- 55.8) ms to (737.7 +/- 131.7), (842.4 +/- 115.6) and (1103.2 +/- 96.3) ms respectively (P < 0.05, P < 0.01, P < 0.01), and increased I(Ca-L) of guinea pig cardiac ventricular myocytes as well as the respectively cytosolic [Ca(2+)]i. Calcium channel blocking agent can cut-out the effect.


CONCLUSIONS
As(2)O(3) intravenous infusion at conventional doses can cause tachycardia and prolong QT interval. The probable mechanism might be that As(2)O(3) affects the ion channels and cytosolic calcium.
The First Clinical Medical College of Harbin Medical University, Harbin 150001, China.
Jin
J
Zhou
Ran
R
Meng
Ying
Y
Liu
Wei
W
Wang
Bao-xin
BX
Li
Bao-feng
BF
Yang
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects* / Q000097:blood; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects; D006224:Cricetinae; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D010087:Oxides / Q000009:adverse effects* / Q000097:blood
D000970:Antineoplastic Agents; D001152:Arsenicals; D020746:Calcium Channels, L-Type; D010087:Oxides; D000077237:Arsenic Trioxide; D002118:Calcium