Progressive impairment of brain oxidative metabolism reversed by reperfusion following middle cerebral artery occlusion in anaesthetized baboons.

ABSTRACT

A better understanding of the temporospatial evolution of ischaemic brain tissue towards necrosis would be of crucial value to establish and validate therapeutic strategies for stroke in man. By means of sequential positron emission tomographic (PET) studies performed through the acute to the chronic stages of infarction, we addressed the question of the effect of 6 h temporary occlusion of the middle cerebral artery (MCAO) on the evolution of the volume of severely hypometabolic tissue in anaesthetized baboons and compared it to that reported previously in permanently occluded baboons. Thirteen anaesthetized baboons underwent serial PET (15O steady-state technique) examinations before and 1, 4, 7, 24-48 h and 15-62 days following transorbital MCAO. Reperfusion, at 6 h post-occlusion, was assessed by Doppler sonography and cerebral blood flow (CBF) values after clip removal. In each baboon, the infarct volume was calculated by standard histological procedures 20-91 days after MCAO. The severely hypometabolic tissue volume, as defined by a threshold of oxidative metabolism, showed a progressive increase for up to 24-48 h in a not dissimilar manner to that found in baboons with permanent occlusion. However, these hypometabolic volumes regressed in the chronic stage (p < 0.05). Permanent and temporary occluded baboons, when taken together, showed a highly significant relationship between histological and chronic hypometabolic volumes (r = 0.84; p < 0.001). Moreover, the final hypometabolic volume where cerebral metabolic rate of oxygen (CMRO2) was below 40% of contralateral metabolism corresponded well to that of histological infarction volume. We conclude that, in anaesthetized baboons, restoration of blood flow will reverse (even if not immediately) the progressive derangement of metabolism after MCAO and markedly limit the final volume of consolidated infarction.)