Experimental Intracranial Hypertension Research Articles

Critical closing pressure during experimental intracranial hypertension: comparison of three calculation methods

ABSTRACT Objectives: The critical closing pressure (CrCP) defines arterial blood pressure below which cerebral arteries collapse. It represents a clinically relevant parameter for the estimation of cerebrovascular tone. Although there are few methods to assess CrCP, there is no consensus which of them estimates this parameter most accurately. The aim of present retrospective, experimental study was to compare three methods of CrCP estimation: conventional Aaslid’s formula and methods based on the cerebrovascular impedance: the established continuous flow forward (CFF) and a new pulsatile flow forward (PFF) model. Methods: The effects of the following physiological manoeuvres on the CrCP were studied in New Zealand white rabbits: lumbar infusion of Hartmann’s solution to induce mild intracranial hypertension, sympathetic blockade to induce arterial hypotension, and modulation of respiratory tidal volume to induce hypocapnia or hypercapnia. Results: During intracranial hypertension, all CrCP estimates were significantly higher than at baseline, decreased with decreasing ABP and increased with gradual hypocapnia. During hypercapnia, all CrCP estimates were significantly decreased but only in the case of CrCPA the negative, non-physiological values were observed (16% of the cases). The Bland–Altman analysis revealed that a good agreement between each impedance method and Aaslid’s method deteriorated significantly in the low range of the average numerical value of the estimates. Discussion: Our results confirm the limited usage of Aaslid’s formula for the calculation of CrCP. Although both impedance methods seem to be equivalent, the fact that PFF model better describes cerebrovascular hemodynamic allows the recommendation of this model for the calculation of CrCP.

Validation of Pressure Reactivity and Pulse Amplitude Indices against the Lower Limit of Autoregulation, Part I: Experimental Intracranial Hypertension.

The purpose of this study was to provide validation of intracranial pressure (ICP) derived continuous indices of cerebrovascular reactivity against the lower limit of autoregulation (LLA). Utilizing an intracranial hypertension model within white New Zealand rabbits, ICP, transcranial Doppler (TCD), laser Doppler flowmetry (LDF), and arterial blood pressure were recorded. Data were retrospectively analyzed in a cohort of 12 rabbits with adequate signals for interrogating the LLA. We derived continuous indices of cerebrovascular reactivity: PRx (correlation between ICP and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and Lx (correlation between LDF-based cerebral blood flow [CBF] and cerebral perfusion pressure [CPP]). LLA was derived via piecewise linear regression of CPP versus LDF or CPP versus systolic flow velocity (FVs) plots. We then produced error bar plots for PRx, PAx, and Lx against 2.5 mm Hg bins of CPP, to display the relationship between these indices and the LLA. We compared the CPP values at clinically relevant thresholds of PRx and PAx, to the CPP defined at the LLA. Receiver operating curve (ROC) analysis was performed for each index across the LLA using 2.5 mm Hg bins for CPP. The mean LLA was 51.5 ± 8.2 mm Hg. PRx and PAx error bar plots demonstrate that each index correlates with the LLA, becoming progressively more positive below the LLA. Similarly, CPP values at clinically relevant thresholds of PRx and PAx were not statistically different from the CPP derived at the LLA. Finally, ROC analysis indicated that PRx and PAx predicted the LAA, with areas under the curve (AUCs) of 0.795 (95% confidence interval [CI]: 0.731-0.857, p < 0.0001) and 0.703 (95% CI: 0.631-0.775, p < 0.0001), respectively. Both PRx and PAx generally agree with LLA within this experimental model of intracranial hypertension. Further analysis of clinically used indices of autoregulation across the LLA within pure arterial hypotension models is required.

Increased ICP and Its Cerebral Haemodynamic Sequelae.

Increased intracranial pressure (ICP) is a pathological feature of many neurological diseases; however, the local and systemic sequelae of raised ICP are incompletely understood. Using an experimental paradigm, we aimed to describe the cerebrovascular consequences of acute increases in ICP. We assessed cerebral haemodynamics [mean arterial blood pressure (MAP), ICP, laser Doppler flowmetry (LDF), basilar artery Doppler flow velocity (Fv) and estimated vascular wall tension (WT)] in 27 basilar artery-dependent rabbits during experimental (artificial lumbar CSF infusion) intracranial hypertension. WT was estimated as the difference between critical closing pressure and ICP. From baseline (~9 mmHg) to moderate increases in ICP (~41 mmHg), cortical LDF decreased (from 100 to 39.1%, p < 0.001), while mean global Fv was unchanged (from 47 to 45 cm/s, p = 0.38). In addition, MAP increased (from 88.8 to 94.2 mmHg, p < 0.01 and WT decreased (from 19.3 to 9.8 mmHg, p < 0.001). From moderate to high ICP (~75 mmHg), both global Fv and cortical LDF decreased (Fv, from 45 to 31.3 cm/s, p < 0.001; LDF, from 39.1 to 13.3%, p < 0.001) while MAP increased further (94.2 to 114.5 mmHg, p < 0.001) and estimated WT was unchanged (from 9.7 to 9.6 mmHg, p = 0.35). In this analysis, we demonstrate a cortical vulnerability to increases in ICP and two ICP-dependent cerebro-protective mechanisms: with moderate increases in ICP, WT decreases and MAP increases to buffer cerebral perfusion, while with severe increases of ICP, an increased MAP predominates.

Cerebral haemodynamics during experimental intracranial hypertension

Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline (∼9 mmHg; SE 1.5) to moderate intracranial pressure (∼41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p = 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p < 0.01), whereas laser Doppler flowmetry and wall tension decreased (laser Doppler flowmetry 100 to 39.1% p < 0.001; wall tension 19.3 to 9.8 mmHg, p < 0.001). From moderate to high intracranial pressure (∼75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p < 0.001, laser Doppler flowmetry 39.1 to 13.3%, p < 0.001), arterial blood pressure increased still further (94.2 to 114.5 mmHg; p < 0.001), while wall tension was unchanged (9.7 to 9.6 mmHg; p = 0.35).This animal model of acute intracranial hypertension demonstrated two intracranial pressure-dependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients.

Blood flow velocities during experimental intracranial hypertension in pigs

Objectives: A purely hydraulic mechanism consisting in the pulsatile cuff-compression effect, by the cerebrospinal fluid displacement induced by the arterial pulsation, on the final portion of the bridging veins, has recently been hypothesized. This mechanism is able to maintain the constancy of cerebral blood flow (CBF) within the autoregulatory range, thus implying an exact balance between arterial inflow and venous outflow. In this study, we correlated arterial inflow and venous outflow during an experimentally induced condition of intracranial hypertension in pigs.Methods: Mock cerebrospinal fluid (CSF) was progressively infused until a condition of brain tamponade was reached. Blood flow velocities at middle cerebral artery and sagittal sinus sites were evaluated simultaneously.Results: Mean intracranial arterial blood flow velocity (IABFV), mean sagittal sinus blood flow velocity (SSBFV), and pulsatile-IABFV remained almost constant until cerebral perfusion pressure (CPP) dropped below 60–70 mmHg; then, a progressive decrease in mean IABFV and SSBFV, together with an increase in pulsatile-IABFV, was evident.Conclusion: The strict similarity between mean IABFV and SSBFV patterns suggests that CBF decrement is mainly due to a decrease in the venous outflow, which, in turn, produces an obstacle to the arterial inflow. The correspondent increase in pulsatile-IABFV confirms the presence of a distal outflow obstruction. All these findings point towards a purely hydraulic mechanism underlying the cerebral autoregulation which acts at the level of the so-called Starling resistor.

Initiation of high-frequency oscillatory ventilation and its effects upon cerebral circulation in pigs: an experimental study

Current practice at high-frequency oscillatory ventilation (HFOV) initiation is a stepwise increase of the constant applied airway pressure to achieve lung recruitment. We hypothesized that HFOV would lead to more adverse cerebral haemodynamics than does pressure controlled ventilation (PCV) in the presence of experimental intracranial hypertension (IH) and acute lung injury (ALI) in pigs with similar mean airway pressure settings. In 12 anesthetized pigs (24-27 kg) with IH and ALI, mean airway pressure (P(mean)) was increased (to 20, 25, 30 cm H(2)O every 30 min), either with HFOV or with PCV. The order of the two ventilatory modes (cross-over) was randomized. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) (fluorescent microspheres), cerebral metabolism, transpulmonary pressures (P(T)), and blood gases were determined at each P(mean) setting. Our end-points of interest related to the cerebral circulation were ICP, CPP and CBF. CBF and cerebral metabolism were unaffected but there were no differences between the values for HFOV and PCV. ICP increased slightly (HFOV median +1 mm Hg, P<0.05; PCV median +2 mm Hg, P<0.05). At P(mean) setting of 30 cm H(2)O, CPP decreased during HFOV (median -13 mm Hg, P<0.05) and PCV (median -17 mm Hg, P<0.05) paralleled by a decrease of MAP (HFOV median -11 mm Hg, P<0.05; PCV median -13 mm Hg, P<0.05). P(T) increased (HFOV median +8 cm H(2)O, P<0.05; PCV median +8 cm H(2)O, P<0.05). Oxygenation improved and normocapnia maintained by HFOV and PCV. There were no differences between both ventilatory modes. In animals with elevated ICP and ALI, both ventilatory modes had effects upon cerebral haemodynamics. The effects upon cerebral haemodynamics were dependent of the P(T) level without differences between both ventilatory modes at similar P(mean) settings. HFOV seems to be a possible alternative ventilatory strategy when MAP deterioration can be avoided.

Desflurane Increases Intracranial Pressure More and Sevoflurane Less Than Isoflurane in Pigs Subjected to Intracranial Hypertension

Desflurane and sevoflurane may have advantages over isoflurane in neuroanesthesia, but this is still under debate. A porcine model with experimental intracranial hypertension was used for paired comparison of desflurane, sevoflurane, and isoflurane with respect to the effects on cerebral blood flow (CBF), cerebrovascular resistance (CVR), and intracranial pressure (ICP). The agents, given in sequence to each of six pigs, were compared at 0.5 and 1.0 minimal alveolar concentrations (MAC) and three mean arterial blood pressure (MAP) levels (50, 70, and 90 mm Hg) at normocapnia and one MAP level (70 mm Hg) at hypocapnia. MAC for each agent had been previously determined in a standardized manner for comparison reliability. CBF was measured with Xe. MAP was lowered by inflation of a balloon catheter in the inferior caval vein and raised by inflation of a balloon catheter in the descending aorta. ICP was measured intraparenchymally. Two Fogarty catheters positioned extradurally were inflated to a baseline ICP of 20 to 22 mm Hg at 0.2 MAC of each agent. CBF and ICP with the three agents at normocapnia and MAP 70 and 90 mm Hg at both 0.5 and 1.0 MAC were as follows (P < 0.05): desflurane > isoflurane > sevoflurane. None of the agents abolished CO2 reactivity. High-dose desflurane resulted in a higher CBF at hypocapnia than corresponding doses of sevoflurane or isoflurane, but there were no significant differences between the agents in ICP at hypocapnia. The present study showed that desflurane increased ICP more and sevoflurane less than isoflurane during normoventilation, but the differences disappeared with hyperventilation.

Correlation between transcranial Doppler ultrasonography and regional cerebral blood flow in experimental intracranial hypertension.

Transcranial Doppler ultrasonography (TCD) provides useful information on cerebral circulation even under raised intracranial pressure. This study was designed to evaluate the correlation between cerebral blood flow (CBF) and TCD parameters under conditions of boundary intracranial hypertension that can cause brain death. Intracranial pressure was raised by inflation of a supratentorial epidural balloon in cats. Blood flow velocity of the middle cerebral artery was measured transorbitally with microvascular Doppler sonography, and intracranial pressure and CBF were evaluated. In this study, four characteristic flow patterns were observed, appearing in the following order with progressive increases in intracranial pressure: sharp wave, systolic flow, systolic spike, and no flow. These flow patterns showed a significant correlation with flow velocity, CBF, the pulsatility index, and cerebral perfusion pressure. The systolic-spike and no-flow patterns and pulsatility index over 4.0 indicated decreased CBF, under 10% of control values. The critical level of brain circulation can be detected by Doppler sonography, indicating that TCD is available as a tool for the assessment of cerebral circulatory arrest in brain death.

Sumatriptan-induced cerebral vasoconstriction as treatment of experimental intracranial hypertension.

Increased intracranial pressure (ICP) is a major cause of mortality in severe head injuries and pharmacologically induced cerebral vasoconstriction has been suggested as a possible treatment. In the present study a porcine model of increased ICP was utilized to study the changes in cerebral haemodynamics and energy metabolism induced by a selective 5-hydroxytryptamine1 agonist (sumatriptan). ICP was raised by inflation of two balloons covering both parieto-occipital regions extradurally. The animals were randomized into four groups receiving sumatriptan. 0.01 mg.kg-1 (A), 0.03 mg.kg-1 (B), 0.1 mg.kg-1 (C), and 0.5 mg.kg-1 (D) intravenously over 10 min. Measurements of cerebral blood flow (CBF), arterio-venous oxygen content difference (CavO2), and jugular venous pH (vpH) were performed 5, 20, 40, 60, and 75 min after start of the infusion. ICP, mean arterial pressure, and EEG were recorded continuously. Direct effects of sumatriptan were also compared in cortical arteries and veins in vitro. Significant decreases in ICP were obtained in groups A, B, and C while group D exhibited a progressive increase in ICP. Significant reductions in CBF, increase in CavO2, and slowing of EEG were observed in groups B, C, and D. Sumatriptan caused moderate constriction of the arteries and a more pronounced dilatation of veins in vitro. The results indicate that a low dose of sumatriptan has the potential to reduce a raised ICP. High doses of sumatriptan cause a further increase of ICP possibly by dilatation of intracerebral veins.

Effects of dihydroergotamine on cerebral circulation during experimental intracranial hypertension.

Different cerebral vasoconstrictors have recently been suggested for the treatment of raised intracranial pressure (ICP), in patients with severe traumatic brain lesions. Such treatment may be associated with severe side effects. A porcine model simulating an intracranial mass lesion was utilized to examine the haemodynamic cerebral effects of dihydroergotamine (DHE), a recently introduced pharmacological treatment for raised intracranial pressure. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering the parieto-occipital region bilaterally. The animals were randomized into one group with six animals receiving 1.0 mg of DHE i.v. followed by a continuous infusion of 0.2 mg/h (high dose) and another group of six animals receiving 0.15 mg i.v. followed by 0.03 mg/h (low dose). Measurements of cerebral blood flow (CBF) and arterio-venous difference in oxygen content (CaVO2) were performed by 5, 20 and 60 min after the DHE infusion. Intracranial pressure (ICP), mean arterial blood pressure (MAP) and cerebral electrical activity (EEG) were recorded continuously. In both groups infusion of DHE caused a lasting decrease in ICP probably achieved mainly by a decrease in cerebral blood volume due to constriction of both arterial and venous capacitance vessels. In the group treated with high-dose DHE, but not in that given low-dose DHE, a progressive increase in CaVO2, a fall in jugular venous pH and an increase in EEG delta activity were observed indicating cerebral hypoxia. The study supports the view that DHE may be a valuable tool in the pharmacological treatment of increased ICP in traumatic brain lesions but underscores the importance of a proper dosage.

Measurements of Regional Cerebral Blood Flow and Blood Flow Velocity in Experimental Intracranial Hypertension: Infusion via the Cisterna Magna in Rabbits

Measurements of Regional Cerebral Blood Flow and Blood Flow Velocity in Experimental Intracranial Hypertension: Infusion via the Cisterna Magna in Rabbits

Measurements of regional cerebral blood flow and blood flow velocity in experimental intracranial hypertension

Cerebral blood flow velocity, as measured in the intracranial segment of the internal carotid artery by transcranial Doppler sonography via the transorbital route, and regional cerebral blood flow and volume in corresponding cortical areas, as measured by the hydrogen clearance technique, were recorded for eight New Zealand White rabbits subjected to infusion via the cisterna magna to elevate intracranial pressure. In the lower range of autoregulation, that is, at perfusion pressures between 80 and 40 mm Hg and even lower, the changes in cerebral blood flow velocity and cerebral blood flow showed a strong correlation (0.86) under conditions of standard pCO2 (PaCO2 = 35 +/- 2 mm Hg). Autoregulation was exhausted at 40 mm Hg, and the cerebrovascular resistance was minimal. Below this perfusion pressure, the cerebral blood flow and volume dropped sharply, whereas the cerebrovascular resistance gradually increased, indicating that, despite the maximally dilated resistance vessels, intracranial hypertension causes vascular resistance to increase, possibly via blocking of the venous outflow. Our results confirmed that noninvasive and easily (even at bedside) applicable measurements of changes in cerebral blood flow velocity could be a substitute for the cumbersome and expensive isotope measurements of cerebral blood flow in patients with intracranial hypertension.

Experimental intracranial hypertension following cisternal injection of various blood components.

Intracranial pressure (ICP) was recorded in 30 dogs which underwent cisternal injection of blood, serum, red blood cells (RBC). RBC ghosts, oxyhemoglobin or bilirubin. The amount of injection was 8-10 ml of blood or an equivalent volume of blood components. Blood or RBC showed a sustained ICP of 15 to 25 mmHg, and RBC ghosts caused a slight transient rise of ICP. In contrast, oxyhemoglobin or bilirubin induced marked intracranial hypertension up to 60-80 mmHg which was associated with frequent pressure waves. Histological examination disclosed aseptic meningitis at the base of the brain and inflammatory changes in the floor of the fourth ventricle after the injection of oxyhemoglobin or bilirubin. It is suggested that the breakdown products of RBC might be causative factors of the intracranial hypertension following subarachnoid hemorrhage.

Reduction of Experimental Intracranial Hypertension by Lidocaine

Previous animal studies in our laboratory revealed that acute cerebral ischemia induced by air embolism is accompanied by a sharp and pronounced rise in both systemic blood pressure and intracranial pressure. To investigate possible approaches to the treatment of severe intracranial hypertension, we produced cerebral air embolism in anesthetized, ventilated cats by the infusion of air into the vertebral artery. Untreated animals consistently experienced severe acute intracranial hypertension. Pretreating the animals with lidocaine greatly attenuated the intracranial hypertension caused by air embolism. Lidocaine given after the injury was also effective in reducing intracranial pressure. Our results suggest that lidocaine may be a useful agent for reducing intracranial hypertension associated with ischemic or traumatic injuries to the brain.

Reduction of experimental intracranial hypertension by lidocaine

Reduction of experimental intracranial hypertension by lidocaine

Reduction of experimental intracranial hypertension by lidocaine.

Previous animal studies in our laboratory revealed that acute cerebral ischemia induced by air embolism is accompanied by a sharp and pronounced rise in both systemic blood pressure and intracranial pressure. To investigate possible approaches to the treatment of severe intracranial hypertension, we produced cerebral air embolism in anesthetized, ventilated cats by the infusion of air into the vertebral artery. Untreated animals consistently experienced severe acute intracranial hypertension. Pretreating the animals with lidocaine greatly attenuated the intracranial hypertension caused by air embolism. Lidocaine given after the injury was also effective in reducing intracranial pressure. Our results suggest that lidocaine may be a useful agent for reducing intracranial hypertension associated with ischemic or traumatic injuries to the brain.

Experimental study of intracranial hypertension.

The present investigation was made in rabbits and cats with perfusing mock cerebrospinal fluid into fourth ventriculus to produce experimental diffusion intracranial hypertension. Under normoxia and acute hypoxia conditions, the changes in cerebral blood flow, spontaneous electrocortical activity, direct cortical response, electrocardiogram, blood pressure and cerebral perfusion pressure were measured as intracranial hypertension caused by step elevation and abrupt elevation; at the same time, the relationship mentioned above was also investigated. The experimental results are very important to clinic treatment and to the patients suffering from anoxia with intracranial hypertension.

Furosemide and Mannitol in the Treatment of Acute Experimental Intracranial Hypertension

Intracranial hypertension was induced in dogs and a small number of baboons by the inflation of epidural balloons. The resulting increased intracranial pressure (ICP) was treated with standard clinical doses of furosemide (0.7 mg/kg), "mini" doses of mannitol (0.75 g/kg), or both agents in combination. Mannitol consistently and rapidly reduced ICP in all animals. When results were averaged, furosemide used alone caused a slow reduction in ICP, but the results were variable in individual animals--with ICP actually increased in some. When furosemide and mannitol were given together, the ICP fell rapidly and remained low for considerably longer than after either agent alone.

Furosemide and mannitol in the treatment of acute experimental intracranial hypertension

Furosemide and mannitol in the treatment of acute experimental intracranial hypertension

Barbiturate effects on acute experimental intracranial hypertension.

Acute intracranial hypertension was induced in cats by progressive inflation of an epidural balloon. Changes in intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), heart rate (HR), electroencephalogram (EEG), and pupil size were studied in untreated animals and in animals that had received barbiturates at different stages during the experiment. In animals pretreated with barbiturates, the increase in ICP during balloon expansion was significantly less than in untreated animals (p less than 0.001). The CPP, initially higher in untreated animals, was not significantly different (P less than 0.05) as the mass lesion pressure-volume curve exceeded the inflection point. In the postdeflation period, the untreated animals developed a significant increase in ICP, whereas, in the barbiturate-pretreated group, the ICP returned to preinflation values, suggesting a protective effect of barbiturates against postcompression brain swelling. Barbiturates affected ICP and CPP differently in animals with intracranial hypertension due to the presence of an epidural balloon that was maintained inflated compared to those with postdeflation brain swelling. In the latter group, pentobarbital reduced ICP (p less than 0.05) without significantly decreasing the CPP, whereas, in the mass lesion group, barbiturates failed to reduce the ICP and caused a deterioration in CPP (p less than 0.025). Brain gross pathological changes were significantly less in the pretreated animals as compared with all other groups. The results suggest that if barbiturate treatment is to have therapeutic value, the timing of the therapy and the criteria for its initiation should be determined.