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Effect of cerebral perfusion pressure on cerebral cortical microvascular shunting at high intracranial pressure in rats.

ABSTRACT: Recently, we showed that decreasing cerebral perfusion pressure (CPP) from 70 mm Hg to 50 mm Hg and 30 mm Hg by increasing intracranial pressure (ICP) with a fluid reservoir induces a transition from capillary (CAP) to microvascular shunt (MVS) flow in the uninjured rat brain. This transition was associated with tissue hypoxia, increased blood-brain barrier (BBB) permeability, and brain edema. Our aim was to determine whether an increase in CPP would attenuate the transition to MVS flow at high ICP.Rats were subjected to progressive, step-wise increases in ICP of up to 60 mm Hg by an artificial cerebrospinal fluid reservoir connected to the cisterna magna. CPP was maintained at 50, 60, 70, or 80 mm Hg by intravenous dopamine infusion. Microvascular red blood cell flow velocity, BBB integrity (fluorescein dye extravasation), and tissue oxygenation (nicotinamide adenine dinucleotide) were measured by in vivo 2-photon laser scanning microscopy. Doppler cortical flux, rectal and cranial temperatures, ICP, arterial blood pressure, and gases were monitored.The CAP/MVS ratio increased (P<0.05) at higher ICP as CPP was increased from 50 to 80 mm Hg. At an ICP of 30 mm Hg and CPP of 50 mm Hg, the CAP/MVS ratio was 0.6±0.1. At CPP of 60, 70, and 80 mm Hg, the ratio increased to 0.9±0.1, 1.4±0.1, and 1.9±0.1, respectively (mean±SEM; P<0.05). BBB opening and increase of reduced form of nicotinamide adenine dinucleotide occurred at higher ICP as CPP was increased.Increasing CPP at high ICP attenuates the transition from CAP to MVS flow, development of tissue hypoxia, and increased BBB permeability.

SUBMITTER: Bragin DE

PROVIDER: S-EPMC3586667 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Effect of cerebral perfusion pressure on cerebral cortical microvascular shunting at high intracranial pressure in rats.

Bragin Denis E DE Bush Rachel C RC Nemoto Edwin M EM

Stroke 20121129 1

<h4>Background and purpose</h4>Recently, we showed that decreasing cerebral perfusion pressure (CPP) from 70 mm Hg to 50 mm Hg and 30 mm Hg by increasing intracranial pressure (ICP) with a fluid reservoir induces a transition from capillary (CAP) to microvascular shunt (MVS) flow in the uninjured rat brain. This transition was associated with tissue hypoxia, increased blood-brain barrier (BBB) permeability, and brain edema. Our aim was to determine whether an increase in CPP would attenuate the ...[more]

PMID: 23204051

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Project description:OBJECTIVES:The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity. DESIGN:Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy. SETTING:University laboratory. SUBJECTS:Male Sprague-Dawley rats. INTERVENTIONS:At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (? intracranial pressure/? mean arterial pressure) and induced cerebrovascular reactivity (? cerebral blood flow/? mean arterial pressure). MEASUREMENTS AND MAIN RESULTS:At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on intracranial pressure or cerebral blood flow (induced intracranial pressure reactivity = -0.03 ± 0.07 and induced cerebrovascular reactivity = -0.02 ± 0.09), reflecting intact autoregulation. Decreasing cerebral perfusion pressure to 50 mm Hg by increasing intracranial pressure increased induced intracranial pressure reactivity and induced cerebrovascular reactivity to 0.24 ± 0.09 and 0.31 ± 0.13, respectively, reflecting impaired autoregulation (p < 0.05). By static cerebral blood flow, the first significant decrease in cerebral blood flow occurred at a cerebral perfusion pressure of 30 mm Hg (0.71 ± 0.08, p < 0.05). CONCLUSIONS:Critical cerebral perfusion pressure of 50 mm Hg was accurately determined by induced intracranial pressure reactivity and induced cerebrovascular reactivity, whereas the static method failed.

Project description:Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH). Methods: Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression. Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11-0.63 (p = 0.002); OR = 0.18, 0.04-0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15-0.63 (p = 0.001); OR 0.30, 95% CI 0.11-0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01). Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.

Project description:IntroductionElevated intracranial pressure (ICP) and blood components are the main trigger factors starting the complex pathophysiological cascade following subarachnoid hemorrhage (SAH). It is not clear whether they independently contribute to tissue damage or whether their impact cannot be differentiated from each other. We here aimed to establish a rat intracranial hypertension model that allows distinguishing the effects of these two factors and investigating the relationship between elevated ICP and hypoperfusion very early after SAH.MethodsBlood or four different types of fluids [gelofusine, silicone oil, artificial cerebrospinal fluid (aCSF), aCSF plus xanthan (CX)] were injected into the cisterna magna in anesthetized rats, respectively. Arterial blood pressure, ICP and cerebral blood flow (CBF) were continuously measured up to 6 h after injection. Enzyme-linked immunosorbent assays were performed to measure the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in brain cortex and peripheral blood.ResultsSilicone oil injection caused deaths of almost all animals. Compared to blood, gelofusine resulted in lower peak ICP and lower plateau phase. Artificial CSF reached a comparable ICP peak value but failed to reach the ICP plateau of blood injection. Injection of CX with comparable viscosity as blood reproduced the ICP course of the blood injection group. Compared with the CBF course after blood injection, CX induced a comparable early global ischemia within the first minutes which was followed by a prompt return to baseline level with no further hypoperfusion despite an equal ICP course. The inflammatory response within the tissue did not differ between blood or blood-substitute injection. The systemic inflammation was significantly more pronounced in the CX injection group compared with the other fluids including blood.DiscussionBy cisterna magna injection of blood substitution fluids, we established a subarachnoid space occupying rat model that exactly mimicked the course of ICP in the first 6 h following blood injection. Fluids lacking blood components did not induce the typical prolonged hypoperfusion occurring after blood-injection in this very early phase. Our study strongly suggests that blood components rather than elevated ICP play an important role for early hypoperfusion events in SAH.

Project description:ObjectivesTargets for treatment of raised intracranial pressure or decreased cerebral perfusion pressure in pediatric neurocritical care are not well defined. Current pediatric guidelines, based on traumatic brain injury, suggest an intracranial pressure target of less than 20 mm Hg and cerebral perfusion pressure minimum of 40-50 mm Hg, with possible age dependence of cerebral perfusion pressure. We sought to define intracranial pressure and cerebral perfusion pressure thresholds associated with inhospital mortality across a large single-center pediatric neurocritical care cohort.DesignRetrospective chart review.SettingPICU, single quaternary-care center.PatientsIndividuals receiving intracranial pressure monitoring from January 2012 to December 2016.InterventionsNone.Measurements and main resultsIntracranial pressure and cerebral perfusion pressure measurements from 262 neurocritical care patients (87 traumatic brain injury and 175 nontraumatic brain injury; 63% male; 8.3 ± 5.8 yr; mortality 11.1%). Mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.75 and 0.64, respectively, for association of inhospital mortality. Cerebral perfusion pressure cut points increased with age (< 2 yr = 47, 2 to < 8 yr = 58 mm Hg, ≥ 8 yr = 73 mm Hg). In the traumatic brain injury subset, mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.70 and 0.78, respectively, for association of inhospital mortality. Traumatic brain injury cerebral perfusion pressure cut points increased with age (< 2 yr = 45, 2 to < 8 yr = 57, ≥ 8 yr = 68 mm Hg). Mean intracranial pressure greater than 15 mm Hg, male sex, and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 14.23 [5.55-36.46], 2.77 [1.04-7.39], and 2.57 [1.03-6.38], respectively; all p < 0.05). Mean cerebral perfusion pressure less than 67 mm Hg and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 5.16 [2.05-12.98] and 3.71 [1.55-8.91], respectively; both p < 0.01). In the nontraumatic brain injury subset, mean intracranial pressure had an area under the receiver operating characteristic curve 0.77 with an intracranial pressure cut point of 15 mm Hg, whereas mean cerebral perfusion pressure was not predictive of inhospital mortality.ConclusionsWe identified mean intracranial pressure thresholds, utilizing receiver operating characteristic and regression analyses, associated with inhospital mortality that is below current guidelines-based treatment targets in both traumatic brain injury and nontraumatic brain injury patients, and age-dependent cerebral perfusion pressure thresholds associated with inhospital mortality that were above current guidelines-based targets in traumatic brain injury patients. Further study is warranted to identify data-driven intracranial pressure and cerebral perfusion pressure targets in children undergoing intracranial pressure monitoring, whether for traumatic brain injury or other indications.

Project description:ObjectivesElevated intracranial pressure and inadequate cerebral perfusion pressure may contribute to poor outcomes in hypertensive intraventricular hemorrhage. We characterized the occurrence of elevated intracranial pressure and low cerebral perfusion pressure in obstructive intraventricular hemorrhage requiring extraventricular drainage.DesignProspective observational cohort.SettingICUs of 73 academic hospitals.PatientsFour hundred ninety-nine patients enrolled in the CLEAR III trial, a multicenter, randomized study to determine if extraventricular drainage plus intraventricular alteplase improved outcome versus extraventricular drainage plus saline.InterventionsIntracranial pressure and cerebral perfusion pressure were recorded every 4 hours, analyzed over a range of thresholds, as single readings or spans (≥ 2) of readings after adjustment for intracerebral hemorrhage severity. Impact on 30- and 180-days modified Rankin Scale scores was assessed, and receiver operating curves were analyzed to identify optimal thresholds.Measurements and main resultsOf 21,954 intracranial pressure readings, median interquartile range 12 mm Hg (8-16), 9.7% were greater than 20 mm Hg and 1.8% were greater than 30 mm Hg. Proportion of intracranial pressure readings from greater than 18 to greater than 30 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 70 mm Hg were associated with day-30 mortality and partially mitigated by intraventricular alteplase. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and intracranial pressure greater than 20 mm Hg in spans were associated with both 30-day mortality and 180-day mortality. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 60 mm Hg were associated with poor day-30 modified Rankin Scale, whereas cerebral perfusion pressure less than 65 and less than 75 mm Hg were associated with poor day-180 modified Rankin Scale.ConclusionsElevated intracranial pressure and inadequate cerebral perfusion pressure are not infrequent during extraventricular drainage for severe intraventricular hemorrhage, and level and duration predict higher short-term mortality and long-term mortality. Burden of low cerebral perfusion pressure was also associated with poor short- and long-term outcomes and may be more significant than intracranial pressure. Adverse consequences of intracranial pressure-time burden and cerebral perfusion pressure-time burden should be tested prospectively as potential thresholds for therapeutic intervention.

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Effect of cerebral perfusion pressure on cerebral cortical microvascular shunting at high intracranial pressure in rats.

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Effect of cerebral perfusion pressure on cerebral cortical microvascular shunting at high intracranial pressure in rats.

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