Water and Electrolytes 13 



velop hepatic necrosis, which appears rather suddenly at about 

 seventeen days. McLean prepared slices from the livers of these 

 animals a few days before necrosis appeared and compared their 

 behaviour with normal liver slices. He found that as expected both 

 types of liver slice lost potassium and accumulated sodium and 

 water when placed in cold saline. When transferred to oxygenated 

 Ringer solution at 37°, the normal liver slice reaccumulated potas- 

 sium against a concentration gradient. However, the pre-necrotic 

 liver slices from rats fed a deficient diet failed to do so as early as 

 three days after commencing the diet. Inability to reaccumulate 

 potassium precedes any demonstrable decline in oxygen uptake 

 by at least ten minutes. The addition of phenergan (promethazine 

 HC1, a compound active in permeability phenomena) to the 

 medium restores the ability of pre-necrotic liver slices to reaccumu- 

 late potassium and to extrude sodium and water and prevents 

 the decline in oxygen uptake. The potassium content of livers from 

 dietetically deficient rats is not obviously lowered until necrosis 

 supervenes. Thus these results suggest that the earliest changes in 

 one type of liver injury, namely dietary deficiency, are a failure to 

 maintain electrolyte gradients in adverse circumstances, possibly 

 followed by a similar failure in normal circumstances. The results 

 suggest also that as in the strophanthin experiments, disturbances 

 in water and electrolyte balance may in fact precede abnormalities 

 in energy-yielding metabolic activity and may even precipitate such 

 abnormalities. 



Other results obtained by McLean show that liver cells from rats 

 deficient in vitamin E exhibit a particular readiness to lose potassi- 

 um and to gain sodium in vitro. This behaviour, too, is reversed by 

 the addition of phenergan and related compounds, all of which are 

 anti-oxidants, as is vitamin E itself. These experiments suggest a 

 possible mechanism, other than general metabolic disturbance, for 

 the characteristic changes in electrolyte movement following in- 

 jury. It may be that specific ion-binding groupings on molecules 

 such as phospholipids are especially susceptible to auto-oxidation 

 with or without the intervention of free radicles such as Fe + + . 

 Vitamin E might act as a natural anti-oxidant to prevent this re- 



