THE EFFECT OF IH POTHF.RMIA ON THE ISOLATED 

 PERFlSi:!) RAT LIVER* 



KAlJ'll W. liRALl'R 



The Ijcilance of processes essential to maintenance of life in a honieotherm de- 

 pends upon a complex interplay of chemical and ])hysical factors. Cooling the 

 tissues of such organisms would he expected to lead to a multi})]e dislocation of 

 components of this balance and should he compatihle with survival only under 

 rather special circumstances. .As an example of a highly polyfunctional tissue with 

 a relatively simple i)hysical framework the hA-er should lend itself particularly well 

 to the exploration of these relations. Development of techniques which allow main- 

 taining the isolated rat liver outside the hody as a functioning organ for well over 

 a day' allows us to study the effects of hypothermia on this mammalian organ in 

 the ahsence of the circulatory and regulatory complications likely to ensue when 

 chilling a whole animal. I should like to report here on results obtained to date in 

 this field, and to discuss their jjearing upon problems of the physiology of the hypo- 

 thermic animal. 



Of the physical parameters which determine liver function, the hemodynamics 

 of this organ are the most readily accessible. Elsewhere- we have shown that the 

 flow pressure diagram of the isolated rat liver perfused through the portal vein can 

 be thought of as consisting of three parts : a region in which perfusion pressures 

 determine the number of open channels (opening pressure region), a region in 

 which limited dilation of otherwise open channels determines the flow pressure 

 diagram, and finally at pressures slightly above the physiological range a region 

 where flow is directly proportional to pressure and the liver vasculature behaves as 

 a rigid system of conduits. Lowering the perfusion temperature results in increased 

 resistance to blood flow through the liver. However,_if the flow coordinate is scaled 

 so as to superpose the curves in the region of direct proportionality, the remainder 

 of the flow pressure diagrams also are found to superpose upon each other at 

 perfusion temperatures between 17 and 38° C. at least. This I take to imply that 

 neither the opening pressures nor the dilatation of the vessels of the isolated liver 

 are afTected by cooling ; the flow pressure relations would appear to reflect a change 

 in perfusate viscosity exclusively. Thus, for any given pressure in the rigid conduit 

 region, liver blood flow changes with temperature in the fashion shown in figure L 

 The results yield a straight line on Arrhem'us coordinates between 17 and 38° C. 

 and from the slope of this line an activation energy of 6570 cal. can be calculated 

 for this process. Plotting in the same manner the fluidity of blood (the inverse of 

 viscosity) as measured in an Ostwald viscometer" a similar line is obtained, the 

 molar activation energy this time being about 6400 cal. — substantiallv identical with 

 the above value for the isolated liver. 



I do not yet have any data on the second major group of physical varialjles 

 affecting liver function, those having to do with subdivision of the organ into dif- 



* The opinions or assertions contained herein are those of the writer and are not to be con- 

 strued as official or reflecting the views of the Navy Department or the Naval Establishment at 

 large. 



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