PROCEEDI NGS. OF THE PHYSIOLOGICAL May 2,3, 1925.

Transcription

1 PROCEEDI NGS OF THE PHYSIOLOGICAL May 2,3, SOCIETY, Insulin and sodium aceto-acetate. By J. H. BURN. The appearance of acetone bodies in the blood is usually supposed to be due to their abnormal formation when fat metabolism is deranged. Their presence has been recorded in diabetes, in starvation and in subjects on a carbohydrate-free diet. Marks(l) has recently carried out experiments which suggest that the secretion of the pancreatic hormone is not continuous, but is dependent on a rise of blood sugar above the fasting value. Consequently in starvation, and in subjects on a carbohydrate-free diet, as well as in diabetes, there may be an absence of insulin from the circulating blood. It seemed possible that the occurrence of acetone bodies in these three conditions might be due, not to an abnormal formation, but to the accumulation of normal metabolic products which did not accumulate when insulin was present in the circulation. I have carried out experiments in which sodium aceto-acetate, prepared by Hurtley's method(2), has been injected into the veins of decapitated cats, and have made observations on the effect of insulin on the rate of disappearance of the sodium aceto-acetate from the blood. The following are the details of such an experiment: Cat, 3-1 kgm. Decapitation under ether anesthesia, after which the animal was respired with air. Kidney vessels were tied on each side, and kidneys removed. Blood-pressure recorded from one carotid artery, and the other carotid prepared so that samples of blood could be drawn off. Injection of 30 c.c. of sodium aceto-acetate solution (in all 2-4 gm. ph 7.5) into ext. jug. vein. Samples of 2'0 c.c. blood were withdrawn at intervals and the total acetone bodies determined by the method of van Slyke. and Fitz (3). Total acetone bodies 25 minutes after injection of Na aceto-acetate 54-5 mgms. per 100 c.c. 20,, later ,, units insulin injected (i. v.) 30 minutes later ,,,, ,,,, 250,

2 PROCEEDINGS OF THE PHYS. SOC., MA Y 23, Determination of the blood sugar, before and after the injection of insulin showed that the usual fall of blood sugar was produced by the injection. In the above experiment, as in three others, no effect of insulin on the rate of decline of the total acetone bodies in circulation was observed. The disappearance recorded was closely similar at all stages to the disappearance in control experiments in which no insulin was injected. (1) Marks. Unpublished communication to the Physiological Society. (2) Hurtley. Quart. Journ. Med (3) Van S lyke and Fi t z. Joum. Biol. Chem xvii Vascular reflexes, chiefly in the ear of the rabbit. (Preliminary communication.) By J. N. LANGLEY. The fall of blood-pressure in the rabbit caused by stimulating the depressor nerve is not in any part due to dilatation of the vessels of the ear, for the fall of pressure, though it is sometimes unaccompanied by any visible change in the ear, is usually accompanied by easily visible contraction of the arteries. The contraction is not wholly a passive effect, for it is greater in parts of the ear the sympathetic nerve fibres to which are intact than in those to which the sympathetic nerve fibres have been cut. Similarly the fall of blood-pressure caused by stimulating the central end of the vagus in the cat is usually accompanied by pallor of the nostrils and lips and the pallor is greater on the side with intact sympathetic than in that on which the cervical sympathetic has been cut. The stimulation may also cause pallor of the penis and of the pads of the feet. The results suggest that there are certain afferent fibres proceeding from the viscera which inhibit the part of the vaso-constrictor centre connected with the viscera and excite the part connected with the skin. Whether the excitation is an indirect effect, set up peripherally or centrally by fall of blood-pressure, remains to be determined. The fact that excision of the abdominal viscera does not essentially alter the results, is fairly good evidence that these afferent fibres cause dilatation of the arteries of the muscles. Dr Jarisch is investigating this question and so far he finds that in the rabbit the depressor causes increase of volume of the gastrocnemius muscle. The vagus in the rabbit, as is known, commonly causes a rise of bloodpressure. The effect on the ear varies with the depth of anaesthesia and the strength of the stimulus. At the beginning of an experiment there is b

3 xviii PROCEEDINGS OF THE PHYSIOLOGICAL usually contraction of the ear vessels. Deep ansesthesia and a strong current favour dilatation-and this may be nearly maximal. The dilatation is largely due to a venous state of the blood, caused by cessation of respiration, but, though lessened, it occurs during artificial respiration. In this case also, it appears that the visceral and the cut'aneous circulation may react in opposite ways. The experiments were made on aniesthetised animals; the stimuli were at the rate of 35 to 40 interruptions a second of the primary current. Both vagi were cut. A note on the melanophore dilator action of the pituitary. By H. H. KNAUS, N. B. DREYER and A. J. CLARK. The writers compared the activity of a water soluble pituitary powder, kindly supplied by Messrs Parke Davis, with that of fresh gland extract made by the method of Burn and Dal-. The water soluble powder was stated to have seven times the oxytocic activity of fresh gland, and this figure was confirmed on the isolated uterus of the guinea-pig. Experiments made on pithed cats, with the precautions described by Hogb en, Schlapp and Macdonald(l) showed that 0-2 mgm. of the powder produced the same rise of blood-pressure as did 1-6 mgm. of fresh gland, that is, a ratio of 1 to 8. The powder, however, had a much feebler relative action on the melanophores of the frog. Dose of pituitary in mgfm. per 25 grm. frog Reactions (Black produced by J Very dark fresh gland ] Dark - 3 a INo visible darkening Reactions XBlack produced by J Very dark dry powder Dark 3 2 1,No visible darkening Observations were made on 44 frogs, and the responses were divided into four classes according to their intensity. The frogs were kept exposed to bright daylight, on a white background, in dry glass jars. The results are shown in the table, and indicate that the dried pituitary powder has more than twice and less than three times as strong an action as fresh gland. In another shorter series of experiments another preparation of fresh gland was found to have only one-tenth the oxytocic action of the dried powder, but to have at least half as much melanophore dilator action.

4 SOCIETY, MA Y 23, XiX x We consider that these results provide strong additional evidence for the view that the melanophore dilator principle is distinct from the oxytocic and pressor principles. (1) Hogben, Schlapp and Macdonald. Quart. Journ. of Exp. Phys xiv , The expenses of this research were defrayed in part by a grant from the Government Grant Committee of the Royal Society. The temperature coefficient of muscle viscosity. By J. F. FULTON.. Attention has previously been directed to the fact1 that when recorded with a myograph of high natural frequency the isometric twitch of intact skeletal muscle is characterised by a flat plateau which terminates abruptly (the "angle"). This sudden discontinuity together with the concave shape of the curve of relaxation suggests that the "angle" denotes the point of cessation of contractile activity and that the curve of relaxation represents the viscous return of the muscle to its resting shape. The effect of temperature on the rate of relaxation also favours this inference. In a large number of experiments in which the responses of the same preparation (intact gastrocnemius) have been taken at 10 and 200 the averaged Q1o of the interval between the beginning of the electrical response and the "angle" has been found to lie between 2 00 and 2 10, while the interval from the "angle" to half-relaxation has a Q10 between 1x3 and 1-4. Records from a typical experiment are plotted in Fig s/r 45 0t / (icr) (2o0) Fig. 1. Two twitches from the intact gastrocnemius of a decerebrate frog at 10 and 200 are plotted on the same coordinates in such a way that their respective "angles" fall at the same point. The tension developed in the two was the same so that the only variable component of their I Proc. Roy. Soc. 97 B, b2

5 xx PROCEEDINGS OF THE PHYSIOLOGIGCAL respective phases was duration. It will be seen that the duration of the interval between the electrical response and the "angle" falls from 86 to 43cr with a rise of 10, while the duration of relaxation falls only from 15 to Ila. The total interval between the action current and the beginning of shortening' (phases 3 and 4 of the latent period) is shortened from 10 to 6cr by a rise of 10. Correlations between growth, differentiation and metabolic rate in the chicken embryo. By HENRY A. MURRAY, Jnr. The present results were obtained during the course of a general investigation of physiological ontogeny, in which correlations were made during the embryological period of the chicken between changes in certain physiological phenomena, such as growth and metabolic rates, and in the chemical constitution of the tissues. The period under investigation extended from the 5th to the 19th day of incubation. The phenomena primarily examined were: (1) growth, (2) gross form development, (3) concentration of solids, and (4) chemical differentiation. It was found that there were significant phase differences, i.e. differences in the period when changes were rapid or the reverse. The rates of the first two functions (growth and form) changed rapidly in the beginning, whereas the latter (concentration and differentiation) changed mostly during the last half of incubation. There were then two type rate curves which were almost opposite in form. They showed skew symmetry around a central point. This phase difference was the basis for distinguishing between primary, or gross, integration (growth) which occurred synchronously with primary, or gross, differentiation of form, and secondary, or internal, integration (concentration of solids) which was concomitant with internal differentiation of chemical form. These two groups are comparable to S p e n c e r' s division of the evolutionary process into primary and secondary redistributions. In this report it is being pointed out that they occur at rates which change at different periods in the life span. A distinction on the basis of rate change differences was discovered between the extent of growth and the latent period of growth in culture experiments with tissues from embryos of different ages. Finally, it was found that the katabolic rate as judged by figures for CO2 production was closely correlated with chemical composition. It was found to decrease as the percentage of water diminished, and the concentration of dry substance increased. 1 Journ. Physiol. 59; Proc. Physiol. Soc. xlvi-xlviii

6 SOCIETY, MAY 23, A special form of polarimeter tube. By L. B. WINTER. Identification of phenyl-osazones is much facilitated by determining the specific rotation and observing the mutarotation. When pyridinealcohol mixture is used as the solvent, it is very difficult to make the latter determinations in an ordinary polarimeter tube with small quantities of material; the solution rapidly turns dark in colour by coming in contact with the metal cap; even the most accurately made tube seems to permit enough leakage for this darkening to take place, which was not prevented by fitting asbestos in place of rubber washers. A glass tube approximately 1 dm. in length was fitted at each end with a stopper into which a circle of polished glass had been cemented. A side tube with ordinary stopper is used for filling. It has been found that if the joints are carefully ground leakage is so slight that readings may be taken more than one day after the tube is first filled, and no darkening of the solution takes place. 3 c.c. are required to fill the tube. As it is difficult to determine the length by measurement, the tube is calibrated with a known sugar solution. XXi A correlation of the size of the action current of skeletal muscle with length, tension and initial heat production. By J. F. FULTON. In a previous communication it was pointed out1 that the size of the successive action currents of the intact gastrocnemius and sartorius muscles of the frog varied with the tension developed. Since then the relation between tension and length has been investigated further. In sartorius diminution in size of the action-currents during a short tetanus can be prevented by placing the muscle under high initial stretch and arranging that the response shall be perfectly "isometric." In a completely "isometric" response of gastrocnemius, on the other hand, it is impossible to prevent successive diminution in size of the actioncurrents at any initial tension. This is interpreted as being due to the unpreventable shortening of the fibres in gastrocnemius owing to their diagonal disposition. Since the degree of diminution in size of the actioncurrents increases with increasing "isometric" shortening', and since the tension developed diminishes correspondingly, it is clear that under these circumstances (but cf. 1, p. 414) the size of the action-current as well as the tension developed diminish with the length of the fire. If a muscle is forcibly lengthened during a tetanus the successive action-currents

7 xxii PROCEEDINGS OF THE PHYS. SOC., MAY 23, have been shown to increase in magnitude. Moreover, at maximal shortening of the completely unloaded muscle the size of the successive electrical responses during a tetanus is 50 to 60 p.c. less than when recording an "isometric" response at approximately its resting length. It is evident from this that the size of the electrical responses vary qualitatively, and possibly even quantitatively with the initial heat production of muscle at various lengths as recently described by A. V. Hill. This clearly favours the view of contraction put forward by Hartree and Hill2 (p. 140) in which they assume that a stimulus causes a momentary rise in permeability which is "manifested by the electric change," and, as already pointed out1, it suggests that the size of the action-current is a measure of the initial process of breakdown. 1 Proc. Roy. Soc. 97 B, Journ. Physiol