Early alterations in cerebral hemodynamics, brain metabolism, and blood- brain barrier permeability in experimental intracerebral hemorrhage

Object. The authors sought to ascertain the nature of the hemodynamic and metabolic derangement underlying acute pathophysiological events that occur after intracerebral hemorrhage (ICH). Methods. Cerebral perfusion pressure (CPP), flow velocity (FV) of the middle cerebral artery, and the arteriovenous contents of oxygen and lactate were investigated in 24 dogs subjected to sham operations (Group A, four animals) or intracerebral injections of 3 ml (Group B, 11 animals) or 5 ml (Group C, nine animals) autologous arterial blood. Twelve additional dogs received intravenous injections of 2% Evans blue or trypan blue dye to evaluate blood-brain barrier (BBB) changes. Within 1 hour, animals with ICH exhibited a rise FV associated with significant reductions (p < 0.05) in CPP and the arteriovenous content difference (AVDO₂). In Group C animals significant increases in lactate concentration were found in arterial and superior sagittal sinus (SSS) samples compared with those in the other two groups (p <: 0.05). Additionally, perihematomal dye extravasation was observed in animals subjected to ICH and trypan blue dye injections, with profound and mild leakages in Group C and Group B animals, respectively, but not in Group A and Evans blue dye-injected animals. During the subsequent 4 hours, the FV and AVDO₂ returned to normal in Group B animals, indicating a balanced cerebral metabolic rate for oxygen (CMRO₂) compared with a deranged CMRO₂ in Group C animals due to their lowered FV and AVDO₂. However, no coupling increase in brain lactate clearance in Group C animals accounted for either the early lactate elevation in SSS or the decrease in CMRO₂. Conclusions. Profound reductions in CPP and brain oxygenation after ICH may rapidly exhaust hemodynamic compensation and, thus, impede cerebral homeostasis; however, these reductions only modestly enhance anaerobic glycolysis. Furthermore, the data suggest that a selective increase in permeability, rather than anatomical disruption, of the BBB is involved in the acute pathophysiological events that occur after ICH, which may provide a possible gateway for systemic arterial lactate entering the SSS.