Testing for circadian differences in lethality for intravenous ouabain in male mice.
Using a randomized, balanced design and double-blind methodology, ouabain octahydrate was administered intravenously to male mice at six clock times. Eight runs were conducted using six constant dosage levels. All the dose-response curves at the clock times of 02:30, 06:30, 10:30, 14:30, 18:30 and 22:30 were parallel and no significant differences were noted between the respective LD50 determinations using nomograph methods. Independent chi-square analysis of all lethality data indicated no significant variation in response between clock times and between runs but a very highly significant difference between doses. Using regression methods, onset time for death was shown to vary inversely with log-dosage, but those periods of possible increased susceptibility could not be correlated with a shortened time to death. These findings are consistent with a random variation in lethality in regard to clock time rather than a true circadian pattern. The pooled (N = 576) intravenous LD50 for ouabain octahydrate was 3.75 mg/kg with 95% confidence limits of 3.60-3.90 mg/kg or, when calculated as anhydrous ouabain, 3.01 (2.89-3.13) mg/kg.
Forrest
A B
AB
Department of Physiology and Pharmacology, School of Pharmacy, University of the Pacific, Stockton, CA 95211.
Hawley
J C
JC
Malone
M H
MH
D000818:Animals; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D004311:Double-Blind Method; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010042:Ouabain / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation
D010042:Ouabain