The Acute Phase of Experimental Subarachnoid Hemorrhage: Intracranial Pressure Dynamics and Their Effect on Cerebral Blood Flow and Autoregulation

Abstract

Clinical presentation and neurological outcome in subarachnoid hemorrhage (SAH) is highly variable. Aneurysmal SAH (aSAH) is hallmarked by sudden increase of intracranial pressure (ICP) and acute hypoperfusion contributing to early brain injury (EBI) and worse outcome, while milder or non-aneurysmal SAH with comparable amount of blood are associated with better neurological outcome, possibly due to less dramatic changes in ICP. Acute pressure dynamics may therefore be an important pathophysiological aspect determining neurological complications and outcome. We investigated the influence of ICP variability on acute changes after SAH by modulating injection velocity and composition in an experimental model of SAH. Five hundred microliters of arterial blood (AB) or normal saline (NS) were injected intracisternally over 1 (AB₁, NS₁), 10 (AB_10, NS₁₀), or 30 min (AB₃₀) with monitoring for 6 h (n = 68). Rapid blood injection resulted in highest ICP peaks (AB₁ median 142.7 mmHg [1.Q 116.7-3.Q 230.6], AB₃₀ 33.42 mmHg [18.8-38.3], p < 0.001) and most severe hypoperfusion (AB₁ 16.6% [11.3-30.6], AB₃₀ 44.2% [34.8-59.8]; p < 0.05). However, after 30 min, all blood groups showed comparable ICP elevation and prolonged hypoperfusion. Cerebral autoregulation was disrupted initially due to the immediate ICP increase in all groups except NS₁₀; only AB₁, however, resulted in sustained impairment of autoregulation, as well as early neuronal cell loss. Rapidity and composition of hemorrhage resulted in characteristic hyperacute hemodynamic changes, with comparable hypoperfusion despite different ICP ranges. Only rapid ICP increase was associated with pronounced and early, but sustained disruption of cerebral autoregulation, possibly contributing to EBI.

Keywords: Acute phase; Cerebral autoregulation; Cerebral hypoperfusion; Early brain injury (EBI); Experimental subarachnoid hemorrhage; Intracranial pressure (ICP).