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An enzymatic-radioisotopic assay was used to measure free choline in unextracted tissue. The lowest concentration of free choline in any tissue studied was present in human cerebrospinal fluid (mean, 5.7 microM; range, 1.8 + 31.2 microM). A postmortem increase in concentration of free choline occurred in blood (0.2 nmol/min.ml), kidney (13 nmol/min.g) and liver (22 nmol/min.g) of mice. The concentration of free choline in these tissues was estimated by extrapolation to be 5, 77, and 29 nmol/g (or ml), respectively. Several treatments were found to increase the concentration of free choline. For example, intraperitoneal administration of choline or 2-amino-2-methyl-propanol (a choline oxidase inhibitor) induced an increase in the level of choline i blood, kidneys, liver, and brain of mice, and administration of 2-dimethylaminoethanol (deanol) caused an increase in kidney and liver choline. The level of choline in blood was increased when rats were treated orally with either antibiotics or esters of choline such as phosphorylcholine, glycerylphosphorylcholine, laroylcholine, or propionylcholine. The results show that the concentration of free choline may be regulated by intestinal metabolism, availability of esterified precursors, and activity of enzymes that metabolize choline.

The literature on exercise physiology in the horse with special reference to swimming is briefly reviewed. The use of a pool for swimming horses is described and a technique discussed for the collection of haematologic and haemodynamic data using this form of exercise.

Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Treatment with deanol also caused an increase in the concentration of choline in kidneys, and markedly inhibited the rates of oxidation and phosphorylation of intravenously administered [3H-methyl]choline. In the liver, deanol inhibited the rate of phosphorylation of [3H-methyl]choline, but did not inhibit its rate of oxidation or cause an increase in the level of free choline. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.

Most of the work on transmitter replacement therapy by means of precursor loading has been directed toward manipulation of neurotransmitters synthesized from aromatic amino acids (47). However, beginning in the mid 1970’s, clinical investigators became interested in the use of choline (Ch) to treat disorders in which too little acetylcholine (ACh) was formed in the brain, or in which the formation of an excess of the neurotransmitter was believed to be desirable. This interest in Ch as a therapeutic agent was triggered by basic research showing that the administration of Ch to laboratory animals could cause an increase in the level of ACh in the brain, a phenomenon first described in 1972 by Kuntscherova (32). Although the beneficial effects of Ch in some disorders such as tardive dyskinesia (see 2) may reside in other properties of the molecule (e.g. a direct postsynaptic muscarinic action of Ch has been demonstrated (9,20,31)), there is evidence that part of the effect of Ch is elicited through stimulation of ACh synthesis and release. This evidence is reviewed in the first part of this report.

The cardiorespiratory and metabolic responses to various levels of tethered-swimming were evaluated in 5 sedentary horses. Cardiac output (QQ}) and heart rate (HR) correlated highly (r=0.89 and 0.94 respectively) with work effort (WE) expressed as kg pulled·kg body wt−1·10−2. While swimming, stroke volume (SV) was reduced at the lowest workloads, but increased with increasing WE so that at the highest workloads it had returned to the on-land standing SV. Pressures in the pulmonic as well as on both sides of the systemic circulation were considerably elevated by this form of exercise, although only mean carotid artery pressure (CAP) correlated highly (r=0.83) with WE. During tethered-swimming plasma lactic acid (LA) rose exponentially from 1 to 10 mmol·1−1 with increasing HR over the range 150–200 beats·min−1. Oxygen uptake (\(\dot VO_2 \)) increased linearly (r=0.95) from 25–112 ml·kg−1·min−1. over the WE range of 3.0–7.8 kg pulled·kg body wt−1·10−2. The aerobic capacity of the equine species would appear to be twice that of man. The greater increase in\(\dot VO_2 \) in the exercising horse cannot be explained solely on the basis of increases inQQ}. Therefore alterations in hematocrit, hemoglobin and oxygen extraction appear to play a more important role in the horse during exercise than they do in man.

Varying concentrations of ethyl alcohol were injected either into the left main coronary artery or intravenously in anesthetized intact dogs. Effects of alcohol on intracardiac conduction (by His bundle electrogram) were examined at spontaneous and paced (atrial) heart rates. Alcohol by the intracoronary route prolonged atrioventricular node and intraventricular conduction times by approximately 5 to 15%. These changes preceded a depression of left ventricular systolic pressure and of the rate of rise of left ventricular pressure and an elevation of left ventricular end-diastolic pressure. Intracoronary injections of contrast medium (sodium diatriozoate) or iso-osmolar solutions of sucrose and injections of similar amounts of alcohol in the ascending or descending aorta did not affect intracardiac conduction. Increasing atrial pacing rates resulted in prolongation of atrioventricular nodal conduction intervals, but did not influence intraventricular conduction time. At each pacing rate, alcohol depressed both atrioventricular nodal and intraventricular conduction. The data suggest that alcohol has a direct depressant effect on intracardiac conduction.