DOSAGE OF THE MAMMALIAN HEART BY CHLOROFORM 83 
How little, if at all, the cardiac rhythm is affected by CHC1, is shown well it 
the heart beats in groups. The amplitude of the individual beats is chiefly determined 
by the length of the preceding diastole.* If that be short the following beat is less 
ample, if long more ample. Under CHC1 ; the group-form persists practically 
unchanged (cf. Fig. 13). In some cases, however, CHC1, sets aside a pre-existing 
irregularity manifest as group beats. 
The Dosage for the Heart 
It is the concentration of the CHC1, in the perfused solution which seems to 
practically alone decide the depth of the depression of activity produced. Mere con- 
tinuance of administration of fresh quantities of the drug does not, if the fresh 
quantities do not involve greater concentrations than those already employed, 
aggravate the paralysant action further. In our experiments such high strengths of 
chloroform as 1 50 mgrms. per litre diluting fluid ('Oi 5 per cent. CHC1,) have perfused 
the whole coronary system uninterruptedly for twenty minutes at a time without, in 
all that time, producing the slightest aggravation of the cardiac depression established 
initially in the first ninety seconds. The gradation of the action of the drug seems 
therefore a function of its tension in the solvent. The results of our dosage experi- 
ments suggest that the cardiac tissue exposed to a fluid of a certain CHC1 3 pressure 
takes up almost at once a certain quantity, and that further continued exhibition of 
the drug under the same tension does not lead to further relative absorption of it by 
the tissue. 
In recent years Dr. Waller has demonstrated, more especially by galvano- 
metric records of the action-currents in isolated frog's nerve, the arithmetic grading 
of the depth of chloroform narcosis obtainable by definite grading of the admixtures of 
CHC1 5 with the air of the moist chamber containing the nerve. His presidential ad4r ess 
to the Section of Physiology at the Montreal Meeting of the British Medical Association, 
1897 {Brit. Med. Journal, November 20, 1897), was largely devoted to this theme. In 
it he pointed out the close analogy between frog's heart and frog's nerve in their reaction 
to various anaesthetics. Our results on CHC1 3 dosage in fluid supplied to the 
coronary circulation of the mammalian heart reveal just such a gradation as that found 
by Dr. Waller in nerve treated by chloroform vapour. The possibility of such 
grading of depression by dosage is one on which Dr. Waller 9 has often insisted as 
of practical importance. We are able to confirm it for the dosage of the isolated 
mammalian heart. 
A form of expressing the CHC1 3 dosage, less instructive than that of giving 
its solution concentration, but nevertheless usefully showing its power upon the heart, 
is to give the weight of CHC1 3 , which reduces the heart beat by a definite amount, 
* Cf. R. S. Woodworth, Amer. Jnl. of Physiology, 1902 
