Mitochondrial redox responses to cerebral ischaemia produced by four-vessel occlusion in the rat

Changes in reduction/oxidation (redox) ratios of the initial and terminal members of the mitochondrial respiratory chain (nicotine adenine dinucleotide and cytochrome a,a3) were measured by fluorometry and reflection spectrophotometry in rat cerebral cortex. Three patterns of responses were observed during the transition to global ischaemia produced by electrocoagulation of the vertebral arteries and carotid artery ligation. Most often, arterial occlusion was accompanied by shifts towards reduction of the mitochondrial components followed by partial reoxidation and then further reduction. Less frequently, ischaemia produced reductive shifts of the respiratory chain reactants that rapidly reached maximal values. In some rats, however, arterial, occlusion produced mitochondrial reduction followed by partial or complete reoxidation. ECoG remained suppressed, despite mitochondrial reoxidation, in approximately 1/3 of the latter animals. This study demonstrates that responses to 4-vessel occlusion can vary greatly among animals and suggests that monitoring of signals of ischaemic insult, such as mitochondrial redox status, may offer advantages for assessment of the consequences of ischaemic insult.