Cellular changes with graded limb ischemia and reperfusion.

Following distal arterial and venous cannulations in both hind limbs of 10 dogs, left leg arterial pressure was reduced to less than 50 torr (group I) and 50 to 75 torr (group II). Muscle membrane potential difference (PD) measurements, muscle biopsies, and arterial and venous blood samples were taken at baseline, after 3 hours of ischemia, and following 3 hours of reperfusion. Blood gas tensions and blood and muscle metabolites were measured. Muscle creatine phosphate levels fell during the ischemic period, but the adenosine triphosphate concentration remained normal. The PD fell in both groups during ischemia and declined further after reperfusion (p greater than 0.01). The deterioration in cell membrane function occurred in spite of intracellular energy repletion and persisted after reperfusion. The PD appears to be a more sensitive indicator of ischemia-induced cell dysfunction than levels of blood or intracellular metabolites. The cause of the progressive fall in the membrane potential is uncertain, but it may be due to cytotoxicity produced by oxygen free radicals.