point excited in the abdomen along special nerve trunks to the cardio-inhibitory centre in the medulla, and that this centre manifested its irritation by impulses which passed centrifugally along the pneumogastric trunk to the heart; that is to say, the heart was slowed or stopped reflexly. From such evidence as this the so-called cardioinhibitory fibres of the vagus have come to be regarded as heart-regulating fibres. Their activity, as we know, is not directly essential to the beat of the heart; they are simply the channels through which the heart is made aware of the ever-varying demands which the changing necessities of the whole body make upon its activity.

As was hinted in the beginning of this paper, the experiments performed upon the isolated heart are of peculiar value in this connection, inasmuch as they go to show that variations in the blood pressure, the maintenance of which is the whole object of the heart's work, have, when applied to the heart alone, no essential effect upon its rate of beat. Bearing these facts in mind, it is superfluous to urge the importance of understanding the physiological conditions whose variation can modify the action of the extrinsic heart-regulating apparatus, and of ascertaining the nature of that modification. In the course of the last year there appeared from a foreign laboratory an account of experiments made upon the frog, which suggested to the authors of the present paper some very interesting problems.

In the research referred to this important fact was brought out, viz. that increase of intra-cardiac pressure weakened or annihilated the cardio-inhibitory power of the vagus. If, for instance, by using a certain strength of stimulation of the vagus with normal intracardiac pressure the heart-beat be slowed one-half, by an increase of the intra-cardiac pressure the same strength of stimulus causes a slowing of only one-third in the rate of beat, or may indeed completely subvert the cardio-inhibitory function of the vagus, which, however, again becomes apparent after lowering the pressure.

It is clear that intra-cardiac pressure may be altered in two quite different ways. If we clamp the aorta or constrict its bore the ventricle must pump harder during its systole in order to overcome the added resistance to the outflow from it. Here we have increased the arterial insistence, and the only effect upon the blood pressure within. the heart is to cause an increased tension during the systole of the ventricle; the semilunar valves preventing the pressure within the aorta from exerting any influence upon the heart during the diastole of the latter.

The intra-cardiac diastolic pressure of the ventricle is increased when there is insufficiency of the semilunar valves; and finally, the intra-cardiac diastolic pressure of the whole heart is increased whenever the blood flows into the venous side of the heart under an increase of pressure. But the heart, in its systole and in its diastole, is in two very different physiological conditions, and it seems highly probable that like conditions should have unlike effects upon the activity of the heart according as they are applied during the period of contraction or relaxation.

Such were the ideas in our mind when, enlightened by the experience of Professor Martin, of this University, with similar problems, we undertook to test, first, the main proposition-whether variations of intra-cardiac pressure did affect the cardio-inhibitory function of the vagus; secondly, to discover whether this peculiar effect exerted by increase of intra-cardiac pressure was limited to any particular phase of the heart's action; thirdly, whether this influence of pressure was confined to any one chamber of the heart; and finally, we hoped to throw some light upon the nature of this action which caused such a marked influence on the efficiency of the vagus; whether, for instance, the action was a mechanical one, due to an overstraining of the heart's fibres, or whether the increased pressure so increased the nutrition of the heart that it continued to beat in spite of vagus excitement.

Our method of experimenting is briefly as follows:

The animals chiefly employed were the frog and the terrapin. In these creatures the heart consists of four separate chambers, viz. a single thick-walled ventricle, two auricles, and a venous sinus, formed by the confluence of the great cardiac veins, which receives the venous blood and communicates with the right auricle. The left auricle has no connection with the sinus, and receives blood from the pulmonary vein. The animal was beheaded and pithed, one cannula inserted into the inferior cava, and one into the innominate artery or one of its larger branches, and all the other vessels leading to and from the heart were tied.

A mixture of one volume of whipped calf's blood to two of 75 per cent. of salt solution was used to nourish the heart. The blood flowed from a Mariotte's bottle into the venous cannula under a constant pressure, which could be varied at will by raising or lowering the flask. The arterial cannula was connected with a T tube, one limb of which communicated with a manometer; the other limb was con

out of the heart.

nected with an open rubber tube, through which the blood passed Arterial pressure could be varied by raising or lowering this tube. Both vagi were so prepared that either could be put upon the stimulating electrodes.

Results of experiments:

I. Effect of Variation of Venous Pressure, Arterial Pressure remaining Constant.-In confirmation of the result obtained by a previous observer, it was found that a slight increase of the pressure by which the heart was filled from the flask diminished the inhibitory power of the vagus, when the strength of the stimulating current and the arterial pressure remained constant. Even so slight an increase of venous pressure as was obtained by raising the supply flask onehalf inch so showed itself in the diminished power of the vagus. When the venous pressure was raised to six or eight inches, the vagus usually becomes powerless to stop the heart when excited by weak stimuli; that is, variations of venous pressure (with constant arterial pressure) within what are probably physiological limits, diminish the effectiveness of the cardio-inhibitory fibres of the vagus. The following is an extract from an experiment on a terrapin:

Venous Pressure.

No. Beats in 10 Seconds without No. Beats in 10 Seconds with
Vagus Stimulation.
Vagus Stimulation.

II. Effect of Variation of Arterial Resistance, Venous Pressure remaining Constant.-Without going into figures, it may be stated that variations of arterial pressure (that is, intra-ventricular pressure at the time of ventricular systole) have no effect on the vagus action. III. Effect of Variation of the Diastolic Ventricular Pressure.The arterial cannula was pushed past the semilunar valves until its end lay within the cavity of the ventricle. Increase of arterial resistance in this manner had no effect upon the vagus until blood had made its way backward through the auriculo-ventricular valves into the auricles, thus raising the pressure within them. This indicates (1) that insufliciency of the semilunar valves, while greatly increasing diastolic intra-ventricular pressure, has no influence on vagus inhibition; (2) though with this increase of pressure within the ventricle at its diastole the resistance to the systole of the auri

cles is augmented, there is evidence that the peculiar effect on vagus action of increase of intra-cardiac pressure can only exert itself during diastole of the heart.

IV. Effect of Variations of Pressure within the Sinus and Auricles together, the Ventricle being Excluded.-The cannula was either passed through the ventricle, whose base was ligatured round it into one auricle, or the ventricle was ligatured and cut away, and the outflow accomplished from the left auricle by a cannula in the pulmonary vein. A slight increase of intra-cardiac pressure was soon shown in the diminished efficiency of the vagus. This effect comes out quite as well when the intact heart is treated as a whole.

V. Effect of Variations of Pressure within the Venous Sinus alone, the rest of the Heart being Excluded.—A ligature was in this case tied between the sinus and the auricular part of the heart. Increase of intra-sinous pressure lessens the efficiency of the vagus in the same general manner as is considered above.

We have never been able to obtain results from the isolated auricles, probably because it is impossible to avoid cutting the vagus fibres in process of ligaturing. As a consequence of the above experiments, we would say that variation of intra-cardiac pressure has a very marked effect in modifying the intensity with which the cardioinhibitory fibres of the vagus act on the heart. It has been shown that increase of systolic pressure in the ventricle is not the cause of this influence on the vagus action. It has been made probable that the result is not due to increase of systolic pressure within the auricle, and therefore that the whole heart is affected in this respect by variation of intra-cardiac pressure only during its diastole. It has been found that increase of pressure within the ventricle at its diastole, such as would follow from semilunar insufficiency, has of itself probably no effect on the vagus action. All the effects which variation of intra-cardiac pressure have upon the efficiency of the vagus can be reproduced on the auricles and sinus together, or upon the

sinus alone.

A large number of experiments of the same kind have been made upon the dog; but, though some decided intimation has been gained that in the mammal's heart also increase of the venous pressure diminishes the cardio-inhibitory efficiency of the vagus, the conditions of the mammalian heart are so difficult to regulate, and the vagus so quickly loses its irritability, that no satisfactory results have as yet been obtained.

INFLUENCE OF DIGITALINE ON THE WORK DONE BY THE HEART OF THE "SLIDER" TERRAPIN

(PSEUDEMYS RUGOSA.-SHAW).

BY H. H. DONALDSON, Fellow of the Johns Hopkins University, and MACTIER WARFIELD, A. B.

Mr. President and Gentlemen :

At the suggestion of Professor Martin, Mr. Warfield and myself made some experiments with digitaline on the isolated heart of the "slider" terrapin (Pseudemys rugosa). Certain results of these experiments, bearing on the work done by the heart, we have the honor to present to you.

The mass of the literature on the physiological action of digitaline has appeared within the last thirty years, and is already abundant. It has been found that plants watered with a solution of digitaline wilt, and that the lower animals, such as snails and worms, are poisoned by it. Its influence on the striped muscles has also been studied, but the most attention has been given to its action on the circulatory apparatus. The investigators on this last point are quite agreed that the same effect is produced on the heart whether that organ be isolated or not. (Dyokowsky and Pelikan, Böhm, Fothergill, etc.)

In mammals with the central nervous system intact there is observed under moderate doses a marked rise in blood pressure, which persists even during the slow pulse. Böhm, Traube, Brinton and Winogradoff could not, however, get this result.

This rise of arterial pressure might be due to an increase of work by the heart solely, or it might be due to a narrowing of the arterioles solely, or it might come from the partial action of both these causes. A number of experiments are recorded where, in a frog with his nervous system intact, narrowing of the arterioles in both web and mesentery has been seen coincident with the slow pulse. (Boldt, Briesemann, Fothergill, etc.)

Brinton and Meyer obtained from a dog under digitaline some kymographic tracings which they interpret as showing a contraction