SIMULTANEOUS P-31 NMR-SPECTROSCOPY AND LASER-DOPPLER FLOWMETRY OF RAT-BRAIN DURING GLOBAL-ISCHEMIA AND REPERFUSION

The relationship between blood flow and metabolism was studied in halothane-anaesthetized, normothermic rats submitted to 30 min global ischemia by four-vessel occlusion. Phosphocreatine (PCr), ATP, intracellular pH and intracellular magnesium (pMg) were measured by P-31 NMR spectroscopy, and blood flow by laser Doppler flowmetry. Prior to ischemia the PCr/ATP ratio of fully relaxed spectra was 2.4 +/- 0.3, intracellular pH was 7.26 +/- 0.15 and pMg was 3.26 +/- 0.13. Vascular occlusion led to complete cessation of blood flow in four out of eight rats, and to incomplete ischaemia (< 10% of control) in the other four animals. During vascular occlusion EEG flattened and energy metabolism broke down in all but one animal with a residual blood flow of 8% of control. pH declined to 6.70 +/- 0.08. The speed of electrophysiological and metabolic recovery after 30 min ischemia varied considerably from animal to animal. Variability depended mainly on the recirculation delay (i.e., the interval from vascular release to normalization of blood flow) but was independent of residual blood flow during ischemia, pre-ischemic glucose, ischemic or post-ischemic acidosis, or the degree of post-ischemic hypoperfusion. After 3 h recirculation PCr and intracellular pH returned to normal but pMg was slightly increased, and ATP was reduced by up to 50% in all animals except the rat with incomplete breakdown of energy metabolism during ischemia. The dissociation between PCr and ATP is attributed to a loss of total adenylate, the severity of which depends on the quality of post-ischemic recirculation. The data refute the hypothesis that the quality of post-ischemic metabolic recovery depends mainly on the severity of tissue acidosis but stress the importance of post-ischemic haemodynamic factors for the speed and quality of brain resuscitation.