Quantitative analysis of the effect of ATP-MgCl2 and adenosine-MgCl2 on the extent of necrosis in rat liver after ischemia.

The effect of the administration of ATP-MgCl2 and adenosine-MgCl2 on the volume density of necrosis occurring 24 hr following 60 min of ischemia in rat liver has been studied. The extent of necrosis in the lobes submitted to ischemia has been assayed by morphometric analysis of fresh liver slices incubated in tetranitro BT. The administration of ATP-MgCl2 (1.25 mumole of each solved in 0.5 ml 0.9% NaCl) reduced the volume density of necrotic areas in the liver of a fasted rat from about 15% to almost zero, provided that the compounds are given as a continuous infusion spread over a period of 15 min and the administration is started before the circulatory flow is restored following ischemia. However, the extent of necrosis was not reduced by ATP-MgCl2 administration when ischemia was induced in the liver of a fed rat which showed a more massive necrosis (about 30%). Increasing concentrations of ATP-MgCl2 to 5 mumole did not result in any improvement. Adenosine-MgCl2 reduced the extent of necrosis after ischemia in a fasted rat in the same way as ATP-MgCl2. The conclusion is drawn that ATP as a direct source of energy and adenosine as a substrate for ATP-synthesis can protect the liver against ischemic damage, whereas MgCl2 plays a supporting role.