| Abstract: | The effect of energy substrate depletion and of high lactic acid (LA) load on the development of irreversible cell injury was evaluated in the lateral gastrocnemius muscle of rabbits subjected to 4 hr of tourniquet hindlimb ischemia. Three groups of animals were studied. Group I, high ATP-ischemia, these animals were subjected to 4 hr of ischemia; group II, low ATP--low LA ischemia, in this group the gastrocnemius muscle was electrically stimulated for 5 min during ischemic conditions to reduce the glycogen store, a short reperfusion period was allowed after the stimulation in order to wash out the built up LA, and the muscle was then subjected to 4 hr of ischemia; group III, low ATP--high LA ischemia, in this group glycogen was depleted as in group II, but no reperfusion period was allowed before the 4 hr period of ischemia. In group I, ATP levels were well preserved during the ischemic period, whereas in the substrate-deprived groups (II and III) a rapid depletion of ATP and phosphocreatine (CP) occurred. The LA was twice as high in the "high LA" group (III) as in the "low LA" group (II) during the ischemic period. The extent of injury was evaluated after 24 hr of reperfusion by measuring ATP and CP content, and contractile force and by light microscopy. No or minor cell damage was found in group I. In group III--high LA--no recovery was obtained in any of the variables used for evaluation. In group II--Low LA--there was a certain recovery. ATP and CP increased to about 35% and contractile force to 25% of control. Morphologically about 20% of the muscle cells appeared to be unaffected by the ischemic insult. It is concluded that reduction of the glycogen available for ATP resynthesis during the ischemic period drastically reduces the ability of skeletal muscle to withstand prolonged ischemia. A high LA load seems to amplify the deleterious effects of a low initial substrate level. |
