ISCHEMIA-INDUCED CHANGES IN CEREBRAL MITOCHONDRIAL FREE FATTY-ACIDS, PHOSPHOLIPIDS, AND RESPIRATION IN THE RAT

Changes in the free fatty acid pool size and fatty acyl chain composit ion of mitochondrial membrane phospholipids and their relation to disr uption of mitochondrial function were examined in rat brains after 30 min of cerebral ischemia (Pulsinelli-Brierley model) and 60 min of nor moxic reoxygenation. During ischemia, significant hydrolysis of polyun saturated molecular species from diacyl phosphatidylcholine, particula rly fatty acyl 20:4 (arachidonic acid; 20% decrease) and 22:6 (docosah exaenoic acid; 15% decrease), was observed. Thirty minutes of ischemia caused a 16% loss of 18:2 (linoleic acid) from phosphatidylethanolami ne. Recirculation for 60 min did not return the polyunsaturated fatty acid content of phospholipids to normal. Total content of free fatty a cids increased during ischemia, particularly 18:2 and 22:6, which exhi bited the most dramatic rise. The free fatty acid pool size continued to increase during 60 min of recirculation. The respiratory control ra tio decreased significantly during 30 min of ischemia with no apparent recovery following 60 min of reoxygenation. The degree of free radica l-mediated lipid peroxidation in mitochondria was significantly increa sed during ischemia and reperfusion. It was concluded that (a) 30 min of cerebral ischemia caused differential degradation in each of the ph ospholipid classes and preferential hydrolysis of the polyunsaturated molecular species and (b) 60 min of normoxic reperfusion failed to pro mote reacylation of the mitochondrial phospholipids and restoration of normal respiration.