STUDIES UPON THE SITE OF STIMULATION OF SALIVATION BY INTRAVENTRICULARLY INJECTED PILOCARPINE IN DOGS

¹ From the Department of Surgery of the University of California Medical School, San Francisco

If we have properly evaluated this problem, the demonstration of a significant central stimulation by any intraventricularly injected agent must necessarily depend upon evidence of stimulatory effects earlier in onset and greater in degree than can be accounted for by its passage from the ventricles into the blood. This, coupled with a demonstration that the effectiveness of the intraventricularly injected agent was appreciably diminished following the interruption of the nervous pathways from the center to the peripheral effector, would be conclusive evidence for central stimulation as postulated by Cushing.

Such evidence has been sought in the present study and the negative results conclusively demonstrate that, in the dog, salivation is the result of the peripheral stimulatory effect of pilocarpine, probably upon the gland itself, and that any salivation occurring as a result of central stimulation is at least physiologically negligible.

Our observations do not exclude the possibility of other types of central stimulation by pilocarpine. However, when taken in conjunction with evidence such as that reported by Wilson on the denervated sweat glands in man, and by Kwit and Hatcher upon the seat of the emetic action of pilocarpine, they do suggest that the hypothesis of the stimulation of parasympathetic centers by intraventricularly injected pilocarpine must be critically examined and tested step by step before it can be accepted. A high proportion of the experiments with intraventricularly injected pilocarpine and pituitrin seem to us to be inconclusive because inadequately controlled. There remain a number of observations—such as the relatively early vasodilatation and gastrointestinal reaction obtained by Cushing with both pituitrin and pilocarpine in some of his patients, and the flushing response in monkeys obtained with pituitrin by Light and Bysshe—which would appear to be good evidence in support of Cushing's hypothesis. If, however, pituitrin is sufficiently impure to cast doubt upon the validity of the results obtained with it, or if the stimulatory effect of intraventricularly injected pituitrin should prove to be asphyxial in nature, because of local vasoconstriction, the early reactions in human beings obtained by Cushing in his studies with pilocarpine would be the only strong evidence in favor of his concept of central stimulation. Because of the lack of control studies, even this cannot qualify as conclusive evidence according to the criteria postulated above. It is not certain, from the evidence, that the effects produced are not merely irritative, and capable of occurring occasionally in response to large intraventricular injections of various agents, rather than being the result of a physiological stimulation in the proper sense of the word.