Clinical and experimental study of cardiac effects of conventional dosage arsenic trioxide in APL patients.
- Author:
Jin ZHOU
1
;
Ran MENG
;
Ying LIU
;
Wei WANG
;
Bao-xin LI
;
Bao-feng YANG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Animals; Antineoplastic Agents; adverse effects; Arsenicals; adverse effects; blood; Calcium; metabolism; Calcium Channels, L-Type; drug effects; Cricetinae; Electrocardiography; drug effects; Female; Heart; drug effects; Humans; Leukemia, Promyelocytic, Acute; drug therapy; Male; Oxides; adverse effects; blood
- From: Chinese Journal of Hematology 2004;25(1):31-34
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate cardiac effects of arsenic trioxide (As(2)O(3)) at conventional dosage in acute promyelocytic leukemia (APL) patients.
METHODSThe 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.
RESULTSApproximately 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.
CONCLUSIONAs(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.
