Cisapride於成長心臟造成直接電生理特性之改變
Date Issued
2002
Date
2002
Author(s)
吳美環
DOI
902314B002161
Abstract
Cisapride is widely used to treat the
gastrointestinal motility disorders. However, it has been associated with QT prolongation, torsades de pointes, and cardiac arrest. Only in children, has atrioventrciular block after cisapride also been described. This study uses Langendorff- perfusion to define the direct effects of cisapride (0.03, 0.1, 0.3 and 1 M) on conduction properties of neonatal (< 7 days) and adult (> 3 months) rabbit hearts. At a clinically relevant dose (0.03 M), cisapride slowed the recovery of the His-Purkinje system. At 0.1 M, the refractoriness of His-Purkinje system and the conduction through this system were prolonged. Corrected QT intervals and ventricular refractory period were also lengthened. These parameters were significantly more prolonged in the neonate than in the adult. The level of atrioventricular block at rapid atrial pacing shifted from the AV node to the His-Purkinje system, with an ED50 of 0.06 and 0.52 M in the neonate and the adult, respectively. In the neonate, cisapride even resulted in infranodal atrioventricular block rhythm (ED50 = 0.12 M), but not in the adult. Polymorphic ventricular tachycardia after cisapride was induced in one of seven adults (14%, 0.03 M) and one of seven neonates (14%, 0.1 M). In conclusion, cisapride may affect the refractoriness of cardiac tissue and the His-Purkinje system appears to be the most sensitive. In neonatal hearts, this modification may progress to infranodal atrioventricular block. Such susceptibility to cisapride indicates that the therapeutic safety range used in the young heart should be narrower.
gastrointestinal motility disorders. However, it has been associated with QT prolongation, torsades de pointes, and cardiac arrest. Only in children, has atrioventrciular block after cisapride also been described. This study uses Langendorff- perfusion to define the direct effects of cisapride (0.03, 0.1, 0.3 and 1 M) on conduction properties of neonatal (< 7 days) and adult (> 3 months) rabbit hearts. At a clinically relevant dose (0.03 M), cisapride slowed the recovery of the His-Purkinje system. At 0.1 M, the refractoriness of His-Purkinje system and the conduction through this system were prolonged. Corrected QT intervals and ventricular refractory period were also lengthened. These parameters were significantly more prolonged in the neonate than in the adult. The level of atrioventricular block at rapid atrial pacing shifted from the AV node to the His-Purkinje system, with an ED50 of 0.06 and 0.52 M in the neonate and the adult, respectively. In the neonate, cisapride even resulted in infranodal atrioventricular block rhythm (ED50 = 0.12 M), but not in the adult. Polymorphic ventricular tachycardia after cisapride was induced in one of seven adults (14%, 0.03 M) and one of seven neonates (14%, 0.1 M). In conclusion, cisapride may affect the refractoriness of cardiac tissue and the His-Purkinje system appears to be the most sensitive. In neonatal hearts, this modification may progress to infranodal atrioventricular block. Such susceptibility to cisapride indicates that the therapeutic safety range used in the young heart should be narrower.
Subjects
Cisapride
cardiac conduction system
torsades depointes
QTprolongation
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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