Since the lower two-thirds of the ventricle or apex, as it is usually termed, contains no nerves, it forms a convenient object for ascertaining the action of drugs upon the muscular substance of the heart itself, and has been much used for this purpose.

Fig. 100.   Perfusion cannula, with the anterior part removed so as to show the septum.

Fig. 100. - Perfusion cannula, with the anterior part removed so as to show the septum.

The apparatus usually employed (Fig. 100) consists of a small cannula introduced into the ventricle, which is attached to it by a ligature tightly tied round it at the junction of its upper third with its lower two-thirds. The interior of the cannula is divided into two by a septum which runs longitudinally, and the one half is connected with a flask containing the nutritive fluid with which it is to be supplied, and the other with a small mercurial manometer provided with a float to register its oscillations upon a revolving cylinder.

At first the nutritive fluid is supplied pure to the apex, and after a normal tracing has been obtained the substance to be investigated is added to it.

When saline solution, a .65 per cent. solution of NaCl, is employed, the apex usually stops in diastole for a period varying from a few minutes to an hour and a half. It then begins to pulsate (Fig. 101, a), getting gradually weaker and weaker (Fig. 101, b and c), and finally stops in diastole. When the heart is in this condition its pulsations may be restored by the addition to the chloride of sodium solution of 1 to 10 per cent. of blood, or of serum, or of a solution of the ashes of serum.

1 Separat-Abdk. a. d. Verhandl. d. physiol. Gesellsch. zu Berlin, Jan. 12, 1883.

Minute quantities of several poisons such as delphinine or quinine, or a mixture of atropine and muscarine, also restore the rhythmical pulsations after they have ceased in a heart-apex supplied with NaCl solution. A minute quantity of Na2CO3 or .005 per cent. of NaHO restores or increases the beats for a time1; afterwards the pulsations become again weaker and the heart stops a second time, but it stops in systole and not in diastole.

a

a

b

b

c

c

Fig. 101. - After Ringer. Tracings showing the effect of simple NaCl solution in weakening the pulsations of the apex of the frog's heart. The tracing a was taken soon after the blood was replaced by NaCl solution; b, after a longer period; and c after a still longer time.

Ringer has made the remarkable discovery that when the saline solution is made with ordinary tap-water the beats become prolonged, but the addition of a trace of potash causes them at once to assume their normal character, and a frog's heart may be kept beating for hours together with saline solution made in this way and containing a trace of potash, although the saline solution never does this when made with distilled water. The addition of a minute trace of calcium salt to distilled water produces the same effect as tap-water - the contractions become larger and longer (Fig. 102). When potash is then added, the length of the contractions becomes diminished to the normal without their strength becoming affected, and thus a pure saline solution made with distilled water and with the addition of minute traces of calcium and potassium will keep the heart beating perfectly for hours together.

Fig. 102.   After Ringer. Shows the effect produced upon the beat of the frog's heart fed with Nad solution by the addition of a trace of calcium chloride.

Fig. 102. - After Ringer. Shows the effect produced upon the beat of the frog's heart fed with Nad solution by the addition of a trace of calcium chloride. The beats in this case are induced by an induction shock.

Dilute alkalies added to the saline solution have been shown by Gaskell to cause a tonic contraction of the muscular fibre of the apex, so that it may gradually cease to beat. This contraction may occur whether the apex is pulsating or not. If it remains at rest, a manometer connected with it simply shows a gradual rise in the mercury until the contraction of the apex is complete. If it is beating, the duration of full contraction at each systole becomes longer, and relaxation during diastole less complete, until no diastolic relaxation occurs and the ventricle remains perfectly still in a condition of complete contraction.

1 Gaule, Archiv f. Anat. u. Phys., 1878, p. 295.

Dilute acids have an opposite action to dilute alkalies, and when very dilute acid, e.g. lactic acid, is mixed with the saline solution, it produces a condition of complete relaxation.

Instead of increasing the duration of the systole like alkalies, acids first shorten it and then render it less and less powerful, until contractions cease altogether and the ventricle remains at rest in diastole.

Dilute acids and alkalies counteract each other's effects on the heart, so that after the beats have been very much lowered in force by acids, an alkali will first restore it to its original condition, and then produce its own characteristic effect. The subsequent application of an acid will undo the effect of the alkali, again weakening the beats and again producing dilatation instead of contraction.1

The three alkalies, potash, soda, and ammonia, have all a somewhat similar tendency to increase the tonic contraction of the ventricle. When large doses are given they tend to paralyse the muscle, so that it again dilates after a period of tonic contraction. The paralysing action of potash is much more powerful, and manifests itself much sooner than that of the other two.

The excitability of the muscular fibre is also altered by alkalies. Soda and ammonia increase it, so that a faradaic stimulus applied to the ventricle has much more effect after the application of soda and ammonia than before. Potash has a different effect and diminishes the excitability of the ventricle, although sometimes the diminution may be preceded by a stage of increased excitability.2

A number of poisons act on the muscular fibre of the ventricle like alkalies, others act like acids.

Antiarine, digitalin, helleborin, veratrine, physostigmine, barium, and probably all the substances belonging to the digitalin group, act like alkalies.

Muscarine 3 acts like an acid, and so apparently do also pilocarpine,4 saponine,5 and apomorphine.

Neutral double salts of copper, chloral, iodal, and other members of the chloral group,6 are probably to be classed along with salts of potassium, first exciting and then paralysing the cardiac muscle.

1 Gaskell, Journ. of Physiol., vol. iii. p. 48.

2 Ringer, Ibid., vol. iii. p. 193.

3 Gaskell, Journ. of Physiol., vol. iii. p. 61.

4 Ibid., op. cit.

5 Schmiedeberg, Ludwig's Festgabe, p. 127.

6 Harnack, Archiv f. exp. Path. u. Pharm., Bel. xvii. p. 185.

In classifying cardiac poisons, when we say that some act like acids and others like alkalies, it must be borne in mind that the action though similar is not identical. Although the actions may be generally like one another, they may vary very considerably even in kind, and they certainly vary enormously in degree. Thus the action of barium and veratrine may be very similar, but veratrine is much the more powerful. We find a similar condition in other structures. Thus iodide of ammonium and curarine both paralyse the ends of motor nerves, but an enormously larger amount of the former is required to produce the effect.

That there is considerable similarity in kind, however, between the action of the vegetable alkaloids and inorganic salts is shown by the fact that the action of veratrine may be neutralised by potassium chloride.1

The irritability of the heart is preserved for very different lengths of time in different gases. Thus Castell2 found that the frog's heart continued to beat in oxygen for 12 hours, in nitrogen for 1 hour, in hydrogen for 1 1/4 hour, in carbonic acid for 10 minutes, in nitrous oxide for 5 or 6 minutes, in carbonic oxide for 40 minutes, and in chlorine for 2 minutes.