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.