Dynamic Cerebrovascular and Intracranial Pressure Reactivity Assessment of Impaired Cerebrovascular Autoregulation in Intracranial Hypertension

Abstract

We previously suggested that the discrepancy between a critical cerebral perfusion pressure (CPP) of 30 mmHg, obtained by increasing intracranial pressure (ICP), and 60 mmHg, obtained by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP [1], and that the determination of the critical CPP by the static cerebral blood flow (CBF) autoregulation curve is not valid with intracranial hypertension. Here, we demonstrated that induced dynamic ICP reactivity (iPRx), and cerebrovascular reactivity (CVRx) tests accurately identify the critical CPP in the hypertensive rat brain, which differs from that obtained by the static autoregulation curve. Step changes in CPP from 70 to 50 and 30 mmHg were made by increasing ICP using an artificial cerebrospinal fluid reservoir connected to the cisterna magna. At each CPP, a transient 10-mmHg increase in arterial pressure was induced by bolus intravenous dopamine. iPRx and iCVRx were calculated as ΔICP/Δ mean arterial pressure (MAP) and as ΔCBF/ΔMAP, respectively. The critical CPP at high ICP, obtained by iPRx and iCVRx, is 50 mmHg, where compromised capillary flow, transition of blood flow to nonnutritive microvascular shunts, tissue hypoxia, and brain-blood barrier leakage begin to occur, which is higher than the 30 mmHg determined by static autoregulation.

Keywords: Blood–brain barrier; CBF autoregulation; Cerebral blood flow; Cerebral perfusion pressure; Induced cerebrovascular reactivity; Induced intracranial pressure reactivity; Intracranial pressure; Microvascular shunt; NADH; Rats.

Figure 1

a) Normalized frequency histograms showing normal microvascular red blood cell flow (RBC) velocity distribution at CPP of 70 mmHg (■) and at CPP of 30 mmHg (■). Decrease of CPP by increasing ICP resulted in redistribution of microvascular flow: capillary flow became very slow while higher flow velocity microvascular shunt flow appeared suggesting a shift from capillaries to higher flow velocity and larger MVS. The vertical dashed line demarcates a velocity of 1.0mm/sec. b) Changes in microvascular shunt/capillary flow (MVS/CAP) ratio showing that decrease of CPP by increasing ICP resulted in the transition to MVS flow. c) Graph shows progression of tissue hypoxia reflected by NADH autofluorescence increase during reduction of CPP by ICP elevation. Data a presented as ΔF/Fo, where Fo is NADH at CPP = 70 mmHg. d) Graph illustrates the average of tetramethylrhodamine fluorescence in brain tissue (extravasation) reflecting progression of BBB degradation during reduction of CPP by ICP elevation. Data a presented as ΔF/Fo, where Fo is fluorescence at CPP = 70 mmHg. All data are presented as Mean±SEM, n=10,*=p<0.05, **=p<0.01, ***=p<0.01.

Figure 2

a) Static autoregulation curve of cortical Doppler flux show preserved autoregulation with an increase of ICP at CPP 70 and 50 mmHg and impaired autoregulation at 30 mmHg. b) Negative values of induced cerebrovascular reactivity (iCVRx) at physiological CPP of 70 mmHg indicated normal cerebrovascular reactivity. After ICP elevation, a rise in iCVRx indicated impairment of cerebrovascular reactivity at CPP of 50 mmHg. c) At normal CPP of 70 mmHg, induced intracranial pressure reactivity (iPRx) has zero or negative values, indicating preserved intracranial pressure reactivity. In contrast, when CPP was decreased by ICP increase, an increase in PRx indicated impaired intracranial pressure reactivity at CPP of 50 mmHg. All data are presented as Mean±SEM, n=10,*=p<0.05, **=p<0.01.