CELLULAR AND TISSUE FUNCTION 213 



satche and Prouvost-Danon, 1957), although respiration of the lung slices 

 is depressed fairly strongly. It would appear that malonate interferes with 

 the anaphylactic release of histamine by a mechanism other than a direct 

 effect on the formation or release of histamine. It may be noted that suc- 

 cinate accelerates the oxygen uptake but has no effect on the release of 

 histamine. 



Cardiac Membrane Potentials and Function 



The physiological disturbances produced by malonate have been most 

 thoroughly studied in the heart. Although the effects are often very slight, 

 despite the evident importance of the cycle in the myocardium, under cer- 

 tain conditions the responses to malonate are very interesting. The earliest 

 investigation was made by Forssman and Lindsten (1946) at Lund, who 

 noted a marked discrepancy between the effects of malonate in the whole 

 animal and on isolated hearts. Intravenous injections of malonate at doses 

 around 3.7-7.5 millimoles/kg to cats and rabbits lead to an increase in the 

 venous blood pressure and a fall in the arterial blood pressure, indicating 

 cardiac depression. In rabbits the cardiac failure begins about 20 min after 

 the injection whereas in cats the changes are immediate. In rabbits the 

 heart may stop after 40 min but in cats recovery is the rule. At autopsy 

 the heart is found to be dilated. The effects of malonate on the isolated 

 perfused rabbit heart, however, are rather small and inconsistent (see ac- 

 companying tabulation). Moreover, succinate at the same concentrations 



Malonate °''» ^^^^^^ ^^ 



acts similarly. These are the immediate effects of malonate and it is possible 

 that the heart would recover from this depression after several minutes, as 

 do rabbit atria (Webb, 1950). It is doubtful if these effects are related to 

 inhibition of succinate oxidase; they are more likely ionic actions on the 

 membrane. The reduction in the coronary flow may result from a vascular 

 constriction, but is more probably the response to the decreased functional 

 activity. 



Isolated rabbit atria are depressed only by high concentrations of mal- 

 onate, 30-40 mM producing a 30% decrease in contractile amplitude and 

 rate at 2 min; the depression is temporary, complete recovery being ob- 

 served after 8-10 min (Webb, 1950b). Atria can continue to beat normally 



