Clinical and experimental study of cardiac effects of conventional dosage arsenic trioxide in APL patients / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate cardiac effects of arsenic trioxide (As(2)O(3)) at conventional dosage in acute promyelocytic leukemia (APL) patients.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>