Cave Grant, Sleigh J W
Waikato Clinical School and Hospital, University of Auckland, Hospital Road, Hamilton, New Zealand.
Vet Hum Toxicol. 2003 Oct;45(5):254-5.
Phenytoin remains a commonly used anticonvulsant agent with sodium channel blocking effects. Much of the cardiotoxicity of phenytoin has been attributed to the propylene glycol vehicle, however there is reason to postulate a contribution from sodium channel blockade. The purpose of this paper is to establish whether, in a rodent model, ECG effects of phenytoin toxicity are consistent with sodium channel blockade and whether these effects and mortality can be lessened by pretreatment with hypertonic saline. Forty rats were given the described LD 50 for phenytoin. Animals were pretreated with either hypertonic saline or gelofusine. The ECG was periodically sampled and mortality assessed. The QRS duration increased with phenytoin administration (p<0.001), without any effect from hypertonic saline on this prolongation. The increase in RR Interval (p<0.001) was diminished by hypertonic saline (p<0.01). Mortality was not different between groups. Phenytoin toxicity has ECG effects consistent with its mechanism as a sodium channel blocker. Pretreatment with hypertonic saline protected against bradycardia, but not mortality nor QRS duration prolongation. Further study is warranted to establish whether hypertonic saline has a role in treating phenytoin's toxic cardiac effects.
苯妥英仍然是一种常用的具有钠通道阻滞作用的抗惊厥药物。苯妥英的许多心脏毒性都归因于丙二醇载体，然而，有理由推测钠通道阻滞也有一定作用。本文的目的是确定在啮齿动物模型中，苯妥英毒性对心电图的影响是否与钠通道阻滞一致，以及高渗盐水预处理是否可以减轻这些影响和降低死亡率。给40只大鼠注射了所描述的苯妥英半数致死量。动物分别用高渗盐水或贺斯进行预处理。定期采集心电图并评估死亡率。随着苯妥英的给药，QRS波时限增加（p<0.001），高渗盐水对这种延长没有任何影响。高渗盐水可减轻RR间期的增加（p<0.001）（p<0.01）。各组之间的死亡率没有差异。苯妥英毒性对心电图的影响与其作为钠通道阻滞剂的机制一致。高渗盐水预处理可预防心动过缓，但不能降低死亡率，也不能缩短QRS波时限。有必要进一步研究以确定高渗盐水在治疗苯妥英的心脏毒性作用方面是否有作用。
