ECG features of sodium channel blockade in rodent phenytoin toxicity and effect of hypertonic saline.
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.
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002121:Calcium Channel Blockers / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D010672:Phenytoin / Q000633:toxicity*; D051381:Rats; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D012462:Saline Solution, Hypertonic; D010672:Phenytoin