Cisapride於成長心臟造成直接電生理特性之改變

Cisapride 是相當有效的胃腸蠕動促 進劑，但cisapride 的使用有可能導致QT 間距延長及torsade de pointes 心室頻脈。而 在兒童也有AV block 的個案報告。本研究 利用Langendorff 灌流之兔子心臟模型探討 cisapride 對心臟傳道系統的影響，並進而 測定是否有年齡性之差異。我們發現在臨 床之劑量濃度（0.03μM），cisapride 可延 緩His-Purkinje 系統之恢復。在0.1μM 時， His-Purkinje 系統的不反應期與傳導時間皆 變長，QT 間距與心室不反應期也延長。在 新生兔這些變化顯著比在成兔來的多。此 外，新生兔甚至加入cisapride 後會變成 infranodal AV block 。因此我們推論， cisapride 對心臟傳導系統， 尤其是 His-Purkinje 系統有抑制其興奮性的作用。 未成熟之心臟對cisapride 之敏感度可能更 高，因此在幼兒使用cisapride 應採用較窄 之治療範圍濃度。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 ( 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