Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded.

Pressure within the microvascular bed of the frog mesentery has been recorded continuously with micropressure transducers which have tip diameters ranging between 0.5–5 µ. The mean values of pressure are in the range of those previously reported. The waveform of the pressure pulses in arterioles and metarterioles closely resembles that in the larger arteries. This observation signifies that the vascular walls are considerably stiffer than is generally believed. The stiffness is probably attributable to the constricted vascular smooth muscle.

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Anion conductance and permeability sequences were obtained for frog skeletal muscle membranes from the changes in characteristic resistance and transmembrane potential after the replacement of one anion by another in the bathing solution. Permeability and conductance sequences are the same. The conductance sequence at pH = 7.4 is C1-> Br-> NO > I-> trichloroacetate > benzoate > valerate >butyrate > proprionate > formate > acetate > lactate > benzenesulfonate > isethionate > methylsulfonate > glutamate > cysteate. The anions are divided into two classes: (a) Chloride-like anions (Cl-through trichloroacetate) have membrane conductances that decrease as pH decreases. The last six members of the complete sequence are also chloride like. (b) Benzoate-like anions (benzoate through acetate) have conductances that increase as pH decreases. At pH = 6.7 zinc ions block C1-and benzoate conductances with inhibitory dissociation constants of 0.12 and 0.16 mM, respectively. Chloride-like and benzoate-like anions probably use the same channels. The minimum size of the channel aperture is estimated as 5.5 X 6.5 A from the dimensions of the largest permeating anions. A simple model of the channel qualitatively explains chloridelike and benzoate-like conductance sequences and their dependence on pH.