Effects of Chlordimeform on Cardiovascular Functional Parameters. Part 1. Lethality and Arrhythmogenicity in the Geriatric Rat

摘要

Chlordimeform (CDM), a formamidine pesticide, had a profound effect on the cardiovascular function of geriatric rats. Two-year-old pentobarbital-anesthetized Sprague-Dawley rats (n=8) received sequential intravenous CDM injections of 5, 10, 30, and 60 mg/kg. A control group of rats (n=8) received multiple injections of normal saline vehicle over a similar time period, followed by a single CDM injection of 60 mg/kg. Heart rate (HR), arterial blood pressure (BP), and electrocardiogram (ECG) were monitored for all animals. CDM produced abrupt decreases in HR and BP at all doses. In addition, striking changes in ECG waveforms and intervals and various conduction-related arrhythmias were observed. These acute effects triggered a reflex-mediated overshoot in HR and BP above preinjection levels, followed by a delayed, persistent depression of these parameters. Three animals from the CDM-treated group died after injection of the 30-mg/kg dose, while 60 mg/kg was lethal in the remaining animals. In the majority of cases, death appeared to be due to cardiac arrest.