Modulating effect of body temperature on the toxic response produced by the pesticide chlordimeform in rats.
Previous studies from this laboratory have demonstrated significant deficits in cardiovascular function in rats exposed to the pesticide chlordimeform (CDM) when body core temperature (TCO) was maintained at 37 degrees C. To investigate the role of TCO on CDM toxicity, similar experiments were conducted over a range of TCO values. Adult rats (n = 30) were anesthetized with sodium pentobarbital (35 mg/kg) and randomly assigned to one of six equal groups. Groups were paired and TCO was maintained in the rats in each of the respective group pairs at one of three levels (37, 35, or 33 degrees C). Rats in one group at each temperature level (groups T37, T35, and T33) were injected intraperitoneally with 60 mg/kg of CDM. Animals in the corresponding temperature-matched groups (groups C37, C35, and C33, respectively) received volume-matched injections of normal saline vehicle and served as time-paired controls. The electrocardiogram and heart rate (HR) were monitored throughout the experimental procedure. There was a significant decrease in HR in all CDM-treated groups when compared to the control group animals. The magnitude of the observed cardiac effect was attenuated in the T35 group when compared to that of the other treated groups. Similarly, lethality rates (number of deaths/total) for the T37, T35, and T33 groups were 2/5, 0/5, and 3/5, respectively; there were no deaths among the control-group animals. From these and previous data from this laboratory, we conclude there may be a beneficial effect of moderate hypothermia in rats exposed to toxic agents while more severe hypothermia appears to offer no advantage and may actually exacerbate the toxic effect.
Watkinson
W P
WP
Environmental Toxicology Division, Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Highfill
J W
JW
Gordon
C J
CJ
D000578:Amidines / Q000633:toxicity*; D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D002319:Cardiovascular System / Q000187:drug effects*; D002742:Chlorphenamidine / Q000633:toxicity*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
D000578:Amidines; D002742:Chlorphenamidine