Abstract
The finding of Lundsgaard 1 that monoiodoacetic acid injection into frogs inhibited the production of lactic acid by skeletal muscles on stimulation, without abolishing contraction, has revolutionized theories of the chemical mechanism of muscular contraction. Accordingly, it seemed valuable to prepare for the extension of this work to mammals by determination of the dosage required for the various symptoms, and for death.
Solutions of monoiodoacetic acid, brought to pH 7.2 by addition of sodium hydroxide, were injected intraperitoneally into unanesthetized female albino rats of 130 to 250 gm. weight, the dosage range being from 30 to 400 mg. per kg. body weight. A group of 5 animals received each dose. The rats had been starved for a period of 48 hours previous to injection.
In all animals receiving 120 or more mg. per kg. death occurred within 20 minutes. The time of onset of symptoms varied from 2 minutes with the largest dose to 8 minutes with 120 mg. per kg. The first alteration of behavior was the appearance of marked general hypoactivity, interrupted by sudden attacks of hyperactivity—running, climbing or biting, in which the movements soon became definitely ataxic. Circus movements appeared in a number of cases. Distinct hyperpnea next appeared, which often progressed to a definite inspiratory dyspnea. The hind legs became paralyzed, being dragged in an abducted posture. The animal soon became prostrate, lying on the side and making no righting movements if placed on the back. Occasionally tremors or mild clonic convulsions occurred. During various of the above stages the animals squeaked loudly, if touched or convulsed, in a manner suggesting hypersensitivity. Finally there appeared a violent tonic convulsion involving the whole body, lasting only about 10 seconds, but leaving the animal in extreme rigor in the posture given to it by the convulsion; mouth open, marked opisthotonus, elbows and wrists flexed; digits of fore feet flexed and adducted; hip, knee and ankle extended; digits of hind feet extended and abducted.
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