THE MECHANISM OF TISSUE RESPIRATION 169 
by an accumulation of lactic acid, especially in the liver: also 
those of Araki, who showed that lactic acid appeared in the 
urine of animals poisoned by carbon monoxide, phosphorus, or 
arsenic. 
The writer has obtained further evidence of the incom- 
pleteness of tissue oxidation under abnormal conditions by 
experiments upon excised mammalian kidneys. When these 
organs are perfused with oxygenated Ringer’s solution for ten 
or twelve hours, their vitality gradually diminishes, but the 
processes of tissue oxidation, though gradually becoming feebler 
in magnitude, do not lack completeness, and the respiratory 
quotient remains practically constant at about ‘85. Kidneys 
which previous to perfusion have been heated for half an 
hour to 50° to 60°, or frozen solid and thawed, or been kept 
in a moist chamber for three to nine days after excision, or 
poisoned by hydrocyanic acid, likewise show considerable 
diminution in their gaseous metabolism, but the processes of 
tissue oxidation still remain complete, and the respiratory 
quotient keeps at about ‘85. When, on the other hand, a kidney 
was perfused with oxygenated saline solution containing 
‘06 to 10 per cent. of lactic acid, or ‘005 to ‘025 per cent. of 
free ammonia, its oxygen-absorption power rapidly dimin- 
ished, but its CO.-producing power fell off more rapidly still, 
so that after four to eight hours of perfusion its respiratory 
quotient dropped to -46- 36, z.e. to about half the normal. 
All the experimental evidence available tends to show, there- 
fore, that the processes of tissue oxidation take place in more 
than one stage, and that the earlier stages are more readily 
accomplished than the final stage which leads to the production 
of free CO, How numerous or complex these stages are we 
have no definite means of knowing, but it is by no means 
improbable that they are of a comparatively simple nature. It 
is well known that increased functional activity of muscles or 
other organs, though it may lead to a tenfold increase of oxygen 
absorption and CO, production, has no effect whatever upon their 
nitrogenous metabolism. Hence Verworn supposes that only 
non-nitrogenous groupings or side chains in the ‘biogen 
molecules” of the protoplasm are concerned in the ordinary 
processes of tissue respiration, and he suggests that these side 
chains may be carbohydrate groupings of an aldehyde character. 
Also he supposes that intramolecular oxygen is stored up in the 
