172 GEORGE RALPH MINES. 



(5) through an alteration m the blood pressure (which may affect 



the heart by a local or a central point of attack) due to con- 

 striction or dilatation of arterioles, this being caused either by 

 reflex, central or local action ; 



(6) on the heart muscle itself. 



By an elaborate series of experiments, involving the section of nerves, 

 the use of drugs such as atropine and curare, the enclosure of organs 

 in plethysmographic apparatus ; by taking records of blood pressure 

 and by ventilating the lungs steadily with the aid of a mechanically- 

 driven respiration pump, it would be possible to determine by which of 

 the various possible means the effect of the injected substance on the 

 heart was produced. 



Suppose, now, that by such experiments the point of action of the 

 substance has been traced to the heart muscle itself. (Be it noted that 

 the elucidation of this point has involved the imposition of more and 

 more artificial conditions.) 



The experiment remains of comparatively little value to the physio- 

 logist, who is endeavouring, by the investigation of the effects of 

 substances on the activity of the heart, to learn more about its actual 

 mechanism. For the experiment can only in the vaguest sense be 

 called quantitative. However carefully the dose of the drug is 

 weighed out, the concentration of the substance in the blood reaching 

 the heart cannot be known at all accurately, since the dilution depends 

 not only on the rate at which the injection is made and on the rate of 

 flow in the vein into which the injection is made, but also on the blood 

 flow in all the other veins leading to the heart. Moreover, it is seldom 

 justifiable to assume that the injected substance remains unchanged in 

 the blood. Blood is a highly complex fluid : the carbonates, phosphates, 

 and in particular the proteins present in it, enter into chemical or 

 adsorptive relation with many injected substances. Of course, from 

 a therapeutic standpoint this does not matter. If, for instance, the 

 injection of a particular drug is followed by marked strengthening of 

 the heart-beat, it matters little to the practitioner whether the sub- 

 stance actually presented to the heart as a result of his injection is the 

 same' chemical substance as that which left the hypodermic syringe, or 

 a product of some complex reaction between that substance and the 

 blood or tissue fluids. But when the object is not simply the produc- 

 tion of the effect, but the explanation of how it is produced; when 

 the response of living cells to changes in their chemical environment 

 is being used to throw light on the mechanism and properties of the 

 tissues themselves, it is clearly of the first importance that the change 



