Abstract 22: Increased Cerebral Perfusion Pressure Delays the Microvascular Shunting and Tissue Hypoxia in the Rat Brain at High ICP in a Time Dependent Manner

Abstract

Background: We reported earlier that high intracranial pressure (ICP) in rats is associated with tissue hypoxia and brain edema due to a transition from capillary (CAP) to thoroughfare channel (TFC) non-nutritive shunt flow. Recently we showed that increasing cerebral perfusion pressure (CPP) shifts the transition threshold to a higher ICP. Here we studied the time dependence of the transition to TFC shunt flow at high ICP to determine how long the increased CPP could delay the transition from CAP to TFC shunting Methods: ICP was increased and maintained at 20, 40 or 60 mmHg for three hours by raising an artificial cerebrospinal fluid reservoir connected to a catheter in the cisterna magna while MAP was elevated by i.v. dopamine infusion to keep CPP at 60 or 80 mmHg. Using in vivo 2-photon laser scanning microscopy through a cranial window over the rat parietal cortex, we measured microvascular red blood cells flow velocity (by fluorescein dye) and tissue oxygenation (NADH fluorescence). CAP flow = microvessel flow velocities < 1.0 and TFC shunt flow = microvessel flow velocities >1.0 mm/sec. Doppler flow, rectal and cranial temperatures, ICP, arterial blood pressure and arterial blood gases were monitored. Results: Maintenance of CPP at 60 mmHg even at a moderate ICP of 20 mmHg did not prevent a gradual increase in microvascular shunting and tissue hypoxia over 3 hours. However, a CPP of 80 mmHg prevented the transition from CAP to TFC shunting at an ICP of 20 mmHg ( Fig. 1 , p<0.05). At ICP of 40 and 60 mmHg and CPP of 60 and 80 mmHg there was a gradual decrease in the CAP/TFC ratio (increased microvascular TFC shunting) and rise in NADH with time. However at a CPP of 80 mmHg, the gradual increase occurred at later time points and was less detrimental than at CPP of 60 mmHg ( Fig. 1 , p<0.05). Conclusions: Increasing CPP with raised ICP could prevent the transition from CAP to TFC shunt flow and tissue hypoxia for a duration that depends upon the level of CPP. Thus, the transition to shunt flow at a given raised ICP and sustained CPP is time dependent. Our data suggest that increasing CPP above the clinical guideline of 50 to 60 mmHg may be beneficial at high ICP.