Studies on the pathogenesis of ischemic cell injury. XI. P/O ratio and acceptor control.

Acceptor control index, P/O ratio and inner membrane permeability were examined in isolated mitochondria following periods of renal ischemia for 15, 30, 60, 120, and 240 min. It was noted that the P/O ratio remained unchanged until 1-2 h after the onset of ischemia. A similar change was noted in the contraction rate of isolated ischemic mitochondria after swelling in KCl and addition of ATP+Mg2+. Both changes are probably indications of a basic membrane alteration which correlates with the occurrence of irreversibility of cell injury. In contrast, the swelling rate in KCl and the acceptor control index are altered almost simultaneously with the onset of ischemia. Therefore, acceptor control index and the rate of swelling are affected prior to the point of irreversible cell injury. They are not, therefore, good as indicators of irreversible changes in the inner membrane of mitochondria leading to the "point-of-no-return."