92 The Chemistry of the Injured Cell 



because the flavine co-factor required for the first step in fatty-acid 

 catabolism cannot be reoxidised under anaerobic conditions. Hence 

 energy production is seriously curtailed. But in diabetes mellitus, 

 myocardial efficiency is not diminished because the devices for 

 energy production are probably not so severely disturbed and alter- 

 native metabolic pathways are preserved, even though carbo- 

 hydrate, fat and protein metabolism are impaired. In Beri Beri, 

 deficiency of thiamine leads to depletion of tissue co-carboxylase 

 and a block may intervene between pyruvate and acetyl co-enzyme 

 A, thus preventing completion of carbohydrate metabolism through 

 the citric acid cycle. Here blood concentrations of pyruvate and 

 lactate increase and myocardial failure follows because interference 

 with energy production is severe. 



RESPONSE OF THE MYOCARDIAL CELL TO ISCHAEMIA 



We are largely dependent upon animal experiments for our 

 knowledge of what happens to the heart soon after its arterial supply 

 is greatly diminished. Within one hour of such restriction the 

 muscle fibre glycogen is greatly reduced, and a substance that stains 

 with the P.A.S. method (and therefore presumably containing 

 polysaccharide aldehyde groups) appears in the cells (Yokoyama 

 et al, 1955) . Oxygen consumption declines rapidly, but returns to 

 normal levels if coronary flow is restored zvithin 2 hours of the 

 initial obstruction. After ischaemia for four to five hours the myo- 

 cardium completely loses its ability to extract oxygen from the 

 available supply of blood. It can still extract glucose but pyruvate 

 extraction falls off rapidly and lactate and glucose production 

 greatly increase. These findings suggest that aerobic pathways of 

 metabolism are now failing and that anaerobic mechanisms are in- 

 tervening. 



However, enzyme activity still remains unimpaired. At 

 two hours after coronary occlusion DPN is considerably diminished, 

 but there is no change in co-carboxylase, nor is the succinic acid 

 dehydrogenase or cytochrome-cytochrome oxidase system affected. 

 Lactic and pyruvic dehydrogenases are also conserved for some 

 time. But ionic disturbances set in rapidly and the resting mem- 

 brane potential can no longer be maintained because of failure of 



