地高辛对新生大鼠和成年大鼠的心脏毒性。

Cardiac toxicity of digoxin in newborn and adult rats.

作者信息

Weinhouse E, Kaplanski J, Warszawski D, Danon A, Gorodischer R

出版信息

Pediatr Pharmacol (New York). 1980;1(2):97-103.

Abstract

We investigated the age-specific arrhythmogenic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. The arrhythmogenic dose 50 (AD50) and lethal dose 50 under anesthesia (LD50) were determined using the method of Litchfield and Wilcoxon. AD50 in adults was 13.0 +/- 1.0 mg/kg (X +/- SD) compared with 2.9 +/- 0.3 mg/kg in the newborns (P less than 0.01), and LD50 in adults was 30.0 +/- 1.9 mg/kg compared with 5.0 +/- 0.2 mg/kg in the newborns (P less than 0.01). Arrhythmias appeared earlier in adults (54 +/- 11.5 minutes after digoxin, X +/- SEM) than in newborns (132.2 +/- 11.0 minutes, P less than 0.01). Paroxysmal atrial tachycardia was the predominant arrhythmia in adults (73%), while transient sinus bradycardia appeared in only 9%. In contrast, all newborns with arrhythmias had severe sinus bradycardia and 69% had profound first degree heart block as well. In conclusion, the newborn rat is more sensitive to digoxin toxicity and develops lethal arrhythmias much more readily than the adult.

摘要

我们研究了地高辛对大鼠不同年龄段的致心律失常作用。成年雌性大鼠（n = 26）和1日龄新生大鼠（n = 20）用戊巴比妥麻醉，皮下注射不同剂量的地高辛。地高辛给药后连续监测心电图4.5小时。采用利奇菲尔德和威尔科克森方法确定致心律失常剂量50（AD50）和麻醉下致死剂量50（LD50）。成年大鼠的AD50为13.0 +/- 1.0 mg/kg（X +/- SD），而新生大鼠为2.9 +/- 0.3 mg/kg（P < 0.01）；成年大鼠的LD50为30.0 +/- 1.9 mg/kg，新生大鼠为5.0 +/- 0.2 mg/kg（P < 0.01）。心律失常在成年大鼠中出现得更早（地高辛给药后54 +/- 11.5分钟，X +/- SEM），而在新生大鼠中出现较晚（132.2 +/- 11.0分钟，P < 0.01）。阵发性房性心动过速是成年大鼠中主要的心律失常（73%），而短暂性窦性心动过缓仅占9%。相比之下，所有出现心律失常的新生大鼠均有严重窦性心动过缓，69%还伴有严重一度房室传导阻滞。总之，新生大鼠对地高辛毒性更敏感，比成年大鼠更容易发生致死性心律失常。