Response of internal carotid artery blood flow velocity to fluid challenge under general anesthesia in pediatric patients with moyamoya disease: A prospective observational study.

BACKGROUND: Maintaining cerebral blood flow is important in intraoperative management of moyamoya disease patients. AIMS: To access changes in the carotid artery blood flow velocity in response to fluid challenge, blood pressure, and cardiac output under general anesthesia in pediatric patients with moyamoya disease. METHODS: This observational study included pediatric patients with moyamoya disease undergoing general anesthesia for encephaloduroarteriosynangiosis. Each patient underwent an ultrasound assessment thrice as follows: after anesthetic induction (T1), after fluid challenge (10 ml/kg, T2), and at the end of surgery (T3). The primary outcome was the change in the internal carotid artery blood flow velocity after fluid challenge and was assessed using a paired t-test. The secondary outcomes comprised changes in the internal, external, and common carotid artery blood flow peak velocities after fluid challenge and the factors influencing these changes. RESULTS: We enrolled and analyzed 30 patients with a mean age of 7.2 years. After fluid challenge, the systolic (p = .003) and mean blood pressure (p = .017), stroke volume index (p = .008), and cardiac index (p = .140) were higher than those at T1. However, both internal carotid artery blood flow velocities did not change after fluid challenge (p = .798, mean difference and 95% confidence interval [CI], -1.1 and -10.3 to 8.0 for right, p = .164, mean difference and 95% CI, -5.2 and -12.7 to 2.2 for left). The internal carotid artery blood flow velocity was correlated with the cardiac index, stroke volume index, and mean and diastolic blood pressure, with low significance. CONCLUSIONS: The internal carotid artery blood flow velocity did not increase in pediatric patients with moyamoya disease under general anesthesia, despite fluid challenge and corresponding changes in the blood pressure and cardiac output. Intraoperative hemodynamic management to improve the cerebral blood flow in these patients requires further investigation.

The regional effect of serum hormone levels on cerebral blood flow in healthy nonpregnant women.

Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on the cerebrovascular system in humans remains largely unknown. To address this, we used a multi-modal magnetic resonance imaging (MRI) approach to investigate the link between serum hormones in the follicular phase and luteal phase of the menstrual cycle (MC) with measures of cerebrovascular function (cerebral blood flow [CBF]) and structure (intracranial artery diameter). Fourteen naturally cycling women were recruited and assessed at two-time points of their MC. CBF was derived from pseudo-continuous arterial spin labeling while diameters of the internal carotid and basilar artery was assessed using time of flight magnetic resonance angiography, blood samples were performed after the MRI. Results show that PROG and EST had opposing and spatially distinct effects on CBF: PROG correlated negatively with CBF in anterior brain regions (r = -.86, p < .01), while EST correlations were positive, yet weak and most prominent in posterior areas (r = .78, p < .01). No significant correlations between either hormone or intracranial artery diameter were observed. These results show that EST and PROG have opposing and regionally distinct effects on CBF and that this relationship is likely not due to interactions with large intracranial arteries. Considering that CBF in healthy women appears tightly linked to their current hormonal state, future studies should consider assessing MC-related hormone fluctuations in the design of functional MRI studies in this population.

High-but not moderate-intensity exercise acutely attenuates hypercapnia-induced vasodilation of the internal carotid artery in young men.

PURPOSE: Exercise-induced increases in shear rate (SR) across different exercise intensities may differentially affect hypercapnia-induced vasodilation of the internal carotid artery (ICA), a potential index of cerebrovascular function. We aimed to elucidate the effects of exercise intensity on ICA SR during exercise and post-exercise hypercapnia-induced vasodilation of the ICA in young men. METHODS: Twelve healthy men completed 30 min of cycling at moderate [MIE; 65 ± 5% of age-predicted maximal heart rate (HRmax)] and high (HIE; 85 ± 5% HRmax) intensities. Hypercapnia-induced vasodilation was induced by 3 min of hypercapnia (target end-tidal partial pressure of CO2 + 10 mmHg) and was assessed at pre-exercise, 5 min and 60 min after exercise. Doppler ultrasound was used to measure ICA diameter and blood velocity during exercise and hypercapnia tests. RESULTS: SR was not altered during either exercise (interaction and main effects of time; both P > 0.05). ICA conductance decreased during HIE from resting values (5.1 ± 1.3 to 3.2 ± 1.0 mL·min-1·mmHg-1; P < 0.01) but not during MIE (5.0 ± 1.3 to 4.0 ± 0.8 mL·min-1·mmHg-1; P = 0.11). Consequently, hypercapnia-induced vasodilation declined immediately after HIE (6.9 ± 1.7% to 4.0 ± 1.4%; P < 0.01), but not after MIE (7.2 ± 2.1% to 7.3 ± 1.8%; P > 0.05). Sixty minutes after exercise, hypercapnia-induced vasodilation returned to baseline values in both trials (MIE 8.0 ± 3.1%; HIE 6.4 ± 2.9%; both P > 0.05). CONCLUSION: The present study showed blunted hypercapnia-induced vasodilation of the ICA immediately after high-intensity exercise, but not a moderate-intensity exercise in young men. Given that the acute response is partly linked to the adaptive response in the peripheral endothelial function, the effects of aerobic training on cerebrovascular health may vary depending on exercise intensity.

Parasympathetic brainstem origin sites of triggered external and internal carotid vasodilation are not distributed topographically in the rat.

Cranial parasympathetic activation produces vasodilation in the head and neck region, but little is known about its central and peripheral mechanisms. This study was conducted to examine whether external and internal carotid-vasodilation origin sites triggered by chemical stimulation are distributed topographically in the parasympathetic brainstems of anesthetized rats, and to examine the effects of peripheral receptors on vasodilation. Microinjection of the neuromodulator candidate l-cysteine revealed that external and internal carotid vasodilation-triggering sites were distributed non-topographically along the full extent of the parasympathetic parvocellular reticular formation (PcRt). Intravenous injection of a muscarinic blocker and a nitric oxide synthase inhibitor abolished external carotid vasodilation, suggesting the peripheral involvement of muscarinic and nitric oxide receptors. Further work is needed to fully understand the PcRt mechanisms underlying timely and appropriate vasodilation to support various cranial functions.

Baseline ASPECTS and hypoperfusion intensity ratio influence the impact of first pass reperfusion on functional outcomes.

BACKGROUND: First pass reperfusion (FPR) has been established as a key performance metric in mechanical thrombectomy (MT). The impact of FPR may be more relevant in fast progressors. We aim to study the impact of baseline Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast CT and hypoperfusion intensity ratio (HIR) on CT perfusion on clinical outcomes after FPR. METHODS: A prospective MT database was reviewed for patients with isolated occlusion of the intracranial internal carotid artery and/or middle cerebral artery M1 segment who underwent MT with complete reperfusion (modified Thrombolyis in Cerebral Infarction score 2c-3) from January 2012 to May 2019. The overall population was divided into ASPECTS >7 versus ≤7 and the subgroup of patients with baseline CT perfusion was divided into HIR <0.3 versus ≥0.3. Univariable and multivariable analyses were performed to establish the predictors of 90-day functional independence (modified Rankin Scale (mRS) ≤2) in each subgroup. RESULTS: A total of 436 patients were included in the analyses. FPR was achieved in 254 (58.3%) patients. ASPECTS modified the effect of FPR on clinical outcomes, with FPR predicting good outcomes in patients with ASPECTS ≤7 (46% vs 29%, adjusted OR 3.748; 95% CI 1.590 to 8.838, p=0.003) while no significant effect was detected in those with ASPECTS >7 (62.3% vs 53.1%, adjusted OR 1.372; 95% CI 0.798 to 2.358, p=0.25). Similarly, FPR predicted good outcomes in patients with HIR ≥0.3 (54.8% vs 41.9%, adjusted OR 2.204; 95% CI 1.148 to 4.233, p=0.01) but not in those with HIR <0.3 (62.9% vs 52.8%, adjusted OR 1.524; 95% CI 0.592 to 3.920, p=0.38). CONCLUSIONS: The impact of FPR on functional outcomes is highly dependent on baseline imaging characteristics, with a more prominent influence in patients presenting with lower ASPECTS and/or higher HIR.

Effects of menstrual cycle and menopause on internal carotid artery shear-mediated dilation in women.

This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21 ± 1 yr), 13 perimenopausal (Peri-M, 49 ± 2 yr), and 10 postmenopausal (Post-M, 65 ± 7 yr) women. Measurements were made twice within the Pre-M group at their early follicular (EF, lower estradiol) and late follicular (LF, higher estradiol) phases. Shear-mediated dilation was induced by 3 min of hypercapnia (target PETCO2 + 10 mmHg from individual baseline) and was calculated as the percent rise in peak diameter relative to baseline diameter. ICA diameter and blood velocity were simultaneously measured by Doppler ultrasound. In Pre-M, shear-mediated dilation was higher during the LF phase than during the EF phase (P < 0.01). Comparing all groups, shear-mediated dilation was reduced across the menopausal transition (P < 0.01), and Pre-M during the LF phase showed the highest value (8.9 ± 1.4%) compared with other groups (Pre-M in EF, 6.4 ± 1.1%; Peri-M, 5.5 ± 1.3%; Post-M, 5.2 ± 1.9%, P < 0.05 for all). Shear-mediated dilation was positively correlated with serum estradiol even after adjustment of age (P < 0.01, r = 0.55, age-adjusted; P = 0.02, r = 0.35). Collectively, these data indicate that controlling the menstrual cycle phase is necessary for the cross-sectional assessments of shear-mediated dilation of the ICA in premenopausal women. Moreover, current findings suggest that a decline in cerebrovascular endothelial function may be partly related to the reduced circulating estrogen levels in peri- and postmenopausal women.NEW & NOTEWORTHY The present study evaluated the effects of the menstrual cycle and menopause stages on the shear-mediated dilation of the ICA, a potential index of cerebrovascular endothelial function, in pre-, peri-, and postmenopausal women. Shear-mediated dilation of the ICA was increased from the low- to high-estradiol phases in naturally cycling premenopausal women and was reduced with advancing menopause stages. Furthermore, lower estradiol was associated with reduced shear-mediated dilation of the ICA, independent of age.

Quantitative Analysis of the Cerebral Vasculature on Magnetic Resonance Angiography.

The arterial connections in the Circle of Willis are a central source of collateral blood flow and play an important role in pathologies such as stroke and mental illness. Analysis of the Circle of Willis and its variants can shed light on optimal methods of diagnosis, treatment planning, surgery, and quantification of outcomes. We developed an automated, standardized, objective, and high-throughput approach for categorizing and quantifying the Circle of Willis vascular anatomy using magnetic resonance angiography images. This automated algorithm for processing of MRA images isolates and automatically identifies key features of the cerebral vasculature such as branching of the internal intracranial internal carotid artery and the basilar artery. Subsequently, physical features of the segments of the anterior cerebral artery were acquired on a sample and intra-patient comparisons were made. We demonstrate the feasibility of using our approach to automatically classify important structures of the Circle of Willis and extract biomarkers from cerebrovasculature. Automated image analysis can provide clinically-relevant vascular features such as aplastic arteries, stenosis, aneurysms, and vessel caliper for endovascular procedures. The developed algorithm could facilitate clinical studies by supporting high-throughput automated analysis of the cerebral vasculature.

Implication of the inferolateral trunk of the cavernous internal CAROTID artery in cranial nerve blood supply: Anatomical study and review of the literature.

The inferolateral trunk (ILT) is one of the two more common branches of the cavernous internal carotid artery (ICA). Its knowledge is important for skull base surgery and endovascular interventional procedures. The ILT is described with superior, anterior and posterior branch, which is the complete form. These branches vascularize the oculomotor, trochlear, trigeminal and abducens nerves into the cavernous sinus and superior orbital fissure (SOF) courses, and through the foramens rotundum and ovale. We performed 21 injected embalmed cadaveric dissections combined with six specimen tomodensitometry. The ILT originates from the horizontal ICA segment and passes above the abducens nerve. Three branches arise from the ILT between the cavernous ICA and the ophthalmic and maxillary nerves initial courses. The main differences with the literature are the number of branches and their cranial nerves' blood supply. The more frequent ILT conformation is the incomplete form with anterior and posterior branch (13/21); the complete form is present in 5/13 sides (38%) and the ILT is in common with the meningohypophyseal trunk in 3/21 (14%) sides. The anterior branch always vascularizes the cranial nerves into the SOF course and most often the maxillary nerve through the foramen rotundum. The posterior branch always vascularizes the mandibular nerve through the foramen ovale course and sometimes the maxillary nerve. This study has demonstrated that there are anastomoses between these branches and arteries arising from the external carotid. This study explains why the sacrifice of a branch of the ILT does not implicate cranial nerve palsy.

Respiratory Variation of Internal Carotid Artery Blood Flow Peak Velocity Measured by Transfontanelle Ultrasound to Predict Fluid Responsiveness in Infants: A Prospective Observational Study.

BACKGROUND: Cranial sonography is a widely used point-of-care modality in infants. The authors evaluated that the respiratory variation of the internal carotid artery blood flow peak velocity as measured using transfontanelle ultrasound can predict fluid responsiveness in infants. METHODS: This prospective observational study included 30 infants undergoing cardiac surgery. Following closure of the sternum, before and after the administration of 10ml · kg crystalloid, the respiratory variation of the aorta blood flow peak velocity, pulse pressure variation, and central venous pressure were obtained. The respiratory variation of the internal carotid artery blood flow peak velocity was measured using transfontanelle ultrasound. Response to fluid administration was defined as an increase in stroke volume index, as measured with transesophageal echocardiography, greater than 15% of baseline. RESULTS: Seventeen subjects (57%) were responders to volume expansion. Before fluid loading, the respiratory variation of the internal carotid artery and the aorta blood flow peak velocity (means ± SD) of the responders were 12.6 ± 3.3% and 16.0 ± 3.8%, and those of the nonresponders were 8.2 ± 3.2% and 10.9 ± 3.5%, respectively. Receiver operating characteristic curve analysis showed that the respiratory variation of the internal carotid artery and the aorta blood flow peak velocity could predict fluid responsiveness; the area under the curve was 0.828 (P < 0.0001; 95% CI, 0.647 to 0.940) and 0.86 (P = 0.0001; 95% CI, 0.684 to 0.959), respectively. The cutoff values of the respiratory variation of the internal carotid artery and the aorta blood flow peak velocity were 7.8% (sensitivity, 94%; specificity, 69%) and 13% (sensitivity, 77%; specificity, 92%), respectively. CONCLUSIONS: The respiratory variation of the internal carotid artery blood flow peak velocity as measured using transfontanelle ultrasound predicted an increase in stroke volume in response to fluid. Further research is required to establish any wider generalizability of the results.

Cerebrovascular and ventilatory responses to acute normobaric hypoxia in girls and women.

Physiological responses to hypoxia in children are incompletely understood. We aimed to characterize cerebrovascular and ventilatory responses to normobaric hypoxia in girls and women. Ten healthy girls (9.9 ± 1.7 years; mean ± SD; Tanner stage 1 and 2) and their mothers (43.9 ± 3.5 years) participated. Internal carotid (ICA) and vertebral artery (VA) velocity, diameter and flow (Duplex ultrasound) was recorded pre- and post-1 h of hypoxic exposure (FIO2 = 0.126;~4000 m) in a normobaric chamber. Ventilation (V˙E) and respiratory drive (VT/TI) expressed as delta change from baseline (∆%), and end-tidal carbon-dioxide (PETCO2) were collected at baseline (BL) and 5, 30 and 60 min of hypoxia (5/30/60 HYP). Heart rate (HR) and oxygen saturation (SpO2) were also collected at these time-points. SpO2 declined similarly in girls (BL-97%; 60HYP-80%, P < 0.05) and women (BL-97%; 60HYP-83%, P < 0.05). Global cerebral blood flow (gCBF) increased in both girls (BL-687; 60HYP-912 mL·min-1, P < 0.05) and women (BL-472; 60HYP-651 mL·min-1, P < 0.01), though the ratio of ICA:VA (%) contribution to gCBF differed significantly (girls, 75:25%; women, 61:39%). The relative increase in V˙E peaked at 30HYP in both girls (27%, P < 0.05) and women (19%, P < 0.05), as did ∆%VT/TI (girls, 41%; women, 27%, P's < 0.05). Tidal volume (VT) increased in both girls and women at 5HYP, remaining elevated above baseline in girls at 30 and 60 HYP, but declined back toward baseline in women. Girls elicit similar increases in gCBF and ventilatory parameters in response to acute hypoxia as women, though the pattern and contributions mediating these responses appear developmentally divergent.

Effect of Cervical Siphon of External and Internal Carotid Arteries.

Variant courses, configuration, and branching pattern of the external and internal carotid arteries, especially when curved in S-shape, are important for hemodynamic changes and clinical implications. Therefore, the aim of the study is to report abnormal cervical siphons observed in external and internal carotid arteries to explore clinical significance by review of literature and hemodynamic changes theoretically.The right common carotid artery bifurcated into external and internal carotid arteries at the level of the upper border of thyroid cartilage in a 70-year-old female cadaver. After bifurcation, the external carotid artery underwent severe tortuosity coursing through 5 bends at points A, B, C, D, and E from its origin to termination and 2 bends at A' and B' in internal carotid artery in the cervical region. The angles between inflow and out flow of the blood at the bends were measured and the change in velocity at each bend was computed for both arteries. Hemodynamic changes were calculated, compared and relevant clinical complications were theoretically correlated.The angles of 20°, 30°, 51°, 52°, 60°, and 28°, 48° were formed by 5 bends of external and 2 bends of internal carotid arteries, respectively. The curved courses of these arteries caused reduction in velocity/stasis, turbulence, and low shear stress. Such kinks might cause stroke, ischemia and mistaken for tumors and abscess in imagery leading to or otherwise producing iatrogenic repercussions. This study will be useful for anatomists, clinicians, and radiologists.

Vascular territorial segmentation and volumetric blood flow measurement using dynamic contrast enhanced magnetic resonance angiography of the brain.

This study proposes a method for territorial segmentation and volumetric flow rate (VFR) distribution measurement of cerebral territories based on time-resolved contrast enhanced magnetic-resonance-angiography (MRA). The method uses an iterative region-growing algorithm based on bolus-arrival-time with increased temporal resolution. Eight territories were segmented: (1) right and (2) left internal carotid arteries, including the middle cerebral artery (ICA+MCA), excluding the anterior cerebral arteries (ACA); (3) right and left ACA (R+L-ACA); (4) right and (5) left external carotid arteries (ECA); (6) right and (7) left posterior cerebral arteries (PCA); and (8) vertebrobasilar territory. VFR percentage, relative to the entire brain (rVFR), was measured based on territorial volume as a function of time. Mean rVFR values of fifteen healthy subjects were: ICA+MCA = 23 ± 2%, R + L-ACA = 17 ± 3%, ECA = 4 ± 2%, PCA = 12 ± 2%, and vertebrobasilar territory = 31 ± 4%. Excluding the ECA-rVFR, which is underestimated, these values are comparable to previously reported values. Six subjects were scanned twice, demonstrating comparable and even higher reproducibility than previously reported using phase-contrast, yet with faster scan time (∼1 min). This method was implemented in one patient with MCA occlusion and one with Moyamoya syndrome scanned before and after bypass surgery, demonstrating its clinical potential for quantitative assessment of the degree of occlusion and the effect of surgery.

Identification of hemodynamically compromised regions by means of cerebral blood volume mapping utilizing computed tomography perfusion imaging.

The aim of the study was to evaluate the potential role of computed tomography perfusion (CTP) imaging in identifying hemodynamically compromised regions in patients with occlusive cerebrovascular disease. Twelve patients diagnosed with either occlusion or severe stenosis of the internal carotid artery or the M1 portion of the middle cerebral artery underwent CTP imaging. The data was analyzed by an automated ROI-determining software. Patients were classified into two subgroups: an asymptomatic group consisting of three patients in whom perfusion pressure distal to the site of occlusion/stenosis (PPdis) could be maintained in spite of the arterial occlusion/stenosis, and a symptomatic group consisting of nine patients in whom PPdis could not be maintained enough to avoid watershed infarction. Four CTP-related parameters were independently compared between the two groups. Significant differences were determined using a two-sample t-test. When statistically significant differences were identified, cut-off points were calculated using ROC curves. Analysis revealed statistically significant differences between the asymptomatic and symptomatic subgroups only in the measure of relCBV (p=0.028). Higher relCBV values were observed in the symptomatic subgroup. ROC curve analysis revealed 1.059 to be the optimal relCBV cut-off value for distinguishing between the asymptomatic and symptomatic subgroups. The data revealed that, in patients whose PPdis is maintained, relCBV remains around 1.00. Conversely, in patients whose PPdis decreased, relCBV increased. From these findings, we conclude that elevation of relCBV as observed using CTP imaging accurately reflects the extent of compensatory vasodilatation involvement and can identify hemodynamically compromised regions.

Internal carotid artery blood flow in healthy awake subjects is reduced by simulated hypovolemia and noninvasive mechanical ventilation.

Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe cerebral damage. This study was designed to assess internal carotid artery blood flow (ICA-BF) during simulated hypovolemia and noninvasive positive pressure ventilation (PPV) in young healthy humans. Beat-by-beat blood velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia and simulated hypovolemia (lower body negative pressure), with or without PPV in 15 awake subjects. Heart rate, plethysmographic finger arterial pressure, respiratory frequency, and end-tidal CO2 (ETCO2) were also recorded. Cardiac index (CI) and ICA-BF were calculated beat-by-beat. Medians and 95% confidence intervals and Wilcoxon signed rank test for paired samples were used to test the difference between conditions. Effects on ICA-BF were modeled by linear mixed-effects regression analysis. During spontaneous breathing, ICA-BF was reduced from normovolemia (247, 202-284 mL/min) to hypovolemia (218, 194-271 mL/min). During combined PPV and hypovolemia, ICA-BF decreased by 15% (200, 152-231 mL/min, P = 0.001). Regression analysis attributed this fall to concurrent reductions in CI (ß: 43.2, SE: 17.1, P = 0.013) and ETCO2 (ß: 32.8, SE: 9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to ICA-BF variance. In healthy awake subjects, ICA-BF was significantly reduced during simulated hypovolemia combined with noninvasive PPV Reductions in CI and ETCO2 had additive effects on ICA-BF reduction. In hypovolemic patients, even low-pressure noninvasive ventilation may cause clinically relevant reductions in CBF, despite maintained arterial blood pressure.

Vascular geometry of the extracranial carotid arteries: an analysis of length, diameter, and tortuosity.

BACKGROUND: Stable access is essential for successful intracranial interventions. Quantifying variations in extracranial carotid arteries may help in the selection and development of access catheters. This study describes the vascular dimensions from the aortic arch to the skull base. METHODS: CT angiography analysis was performed on 100 patients. The lengths, diameters, and tortuosity of the common carotid artery (CCA) and internal carotid artery (ICA) were measured from the aortic arch to the skull base. RESULTS: The mean±SD length of the carotid artery from the aortic arch to the skull base was 22.2±2.2 cm for the right side and 20.8±1.9 cm for the left side (p<0.0001). The length of the right CCA was 13.6±1.2 cm and the length of the left CCA was 12.4±1.4 cm (p<0.0001). The length of the right ICA was 8.6±1.4 cm compared with 8.4±1.4 cm for the left ICA (p=0.3). The ICA length in men and women was 8.9±1.3 cm and 8.2±1.3 cm, respectively (p=0.0001), and the CCA length in men and women was 13.6±1.5 cm and 12.3±1.6 cm, respectively (p<0.0001). The lengths of the CCA and ICA in patients aged ≥60 years were 13.3±1.7 cm and 8.9±1.5 cm, respectively compared with 12.8±1.7 cm and 8.2±1.1 cm, respectively, for patients aged <60 years (p=0.04 for CCA, p=0.0002 for ICA). Tortuosity of the CCA and ICA was 1.2±0.2 and 1.3±0.1, respectively, in patients aged ≥60 years compared with 1.1±0.1 for both the ICA and CCA in patients aged <60 years (p<0.0001 for both). There was a consistent ratio of CCA/ICA length of 1.6±0.3 on the right and 1.5±0.3 on the left (p<0.0001). The arterial diameters did not show any significant difference. CONCLUSIONS: The distance from the aortic arch to the skull base is longer on the right than on the left side. Both the CCA and ICA are longer in men and in patients aged ≥60 years. The tortuosity of both segments significantly increases with age.

Hemodynamic characteristics of large unruptured internal carotid artery aneurysms prior to rupture: a case control study.

OBJECTIVE: Post-ruptured intracranial aneurysm geometry models have been widely used in computational fluid dynamic studies to assess hemodynamic parameters associated with aneurysm rupture. However, their results may not be valid due to the morphological changes of the aneurysm after rupture. Our aim was to identify the hemodynamic features of aneurysms prior to rupture in comparison with unruptured aneurysms. MATERIALS AND METHODS: We retrospectively identified three large unruptured internal carotid artery (ICA) aneurysms (pre-ruptured group) with adequate image quality just before rupture. Matched with the same location and similar size, eight unruptured aneurysms (unruptured group) were selected as controls during the same time period. Flow simulations for these aneurysms were performed to compare differences in hemodynamics. RESULTS: Compared with unruptured aneurysms, pre-ruptured aneurysms had a significantly more irregular aneurysm shape, a higher aspect ratio, and lower aneurysm averaged wall shear stress (WSS) (p=0.024, p=0.048, and p=0.048, respectively). Although pre-ruptured aneurysms had a lower low WSS area and higher Oscillatory Shear Index, these were not statistically significant. CONCLUSIONS: For large unruptured ICA aneurysms, low WSS, higher aspect ratio, and irregular shape were indicators of fatal rupture. Early treatment for such lesions with flow diverter and coils may be the best therapeutic option.

Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17ß-estradiol on isolated canine basilar and internal carotid arteries.

Progesterone and 17ß-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17ß-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17ß-estradiol on KCl- and/or PGF2α-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl2 was also determined. In both arteries progesterone (5.6-180 µM) and 17ß-estradiol (1.8-180 µM): (1) produced concentration-dependent relaxations of KCl- or PGF2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 µM), cycloheximide (10 µM), SQ 22,536 (100 µM) or ODQ (30 µM), potassium channel blockers and ICI 182,780 (only for 17ß-estradiol). In the basilar artery the vasorelaxation induced by 17ß-estradiol was slightly blocked by tetraethylammonium (10mM) and glibenclamide (KATP; 10 µM). In both arteries, progesterone (10-100 µM), 17ß-estradiol (3.1-31 µM) and nifedipine (0.01-1 µM) produced a concentration-dependent blockade of the contraction to CaCl2 (10 µM-10mM). These results suggest that progesterone and 17ß-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca(2+) channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17ß-estradiol in the internal carotid artery; meanwhile KATP channels play a minor role on the effect of 17ß-estradiol in the basilar artery.

MMP-9 gene ablation mitigates hyperhomocystenemia-induced cognition and hearing dysfunction.

Hyperhomocysteinemia (HHcy) is associated with cognitive decline and hearing loss due to vascular dysfunction. Although we have shown that HHcy-induced increased expression of matrix metalloproteinase-9 (MMP-9) is associated with cochlear pathology in cystathionine-ß-synthase heterozygous (CBS(+/-)) mice, it is still unclear whether MMP-9 contributes to functional deficit in cognition and hearing. Therefore, we hypothesize that HHcy-induced MMP-9 activation causes vascular, cerebral and cochlear remodeling resulting in diminished cognition and hearing. Wildtype (WT), CBS(+/-), MMP-9(-/-) and CBS(+/-)/MMP-9(-/-) double knock-out (DKO) mice were genotyped and used. Doppler flowmetry of internal carotid artery (ICA) was performed for peak systolic velocity [PSV], pulsatility index [PI] and resistive index [RI]. Cognitive functions were assessed by Novel Object Recognition Test (NORT) and for cochlear function Auditory brainstem response (ABR) was elicited. Peak systolic velocity, pulsatility and resistive indices of ICA were decreased in CBS(+/-) mice, indicating reduced perfusion. ABR threshold was increased and maximum ABR amplitude and NORT indices (recognition, discrimination) were decreased in CBS(+/-) mice compared to WT and MMP-9(-/-). All these parameters were attenuated in DKO mice suggesting a significant role of MMP-9 in HHcy-induced vascular, neural and cochlear pathophysiology. Regression analysis of PSV with ABR and cognitive parameters revealed significant correlation (0.44-0.58). For the first time, MMP-9 has been correlated directly to functional deficits of brain and cochlea, and found to have a significant role. Our data suggests a dual pathology of HHcy occurring due to a decrease in blood supply (vasculo-neural and vasculo-cochlear) and direct tissue remodeling.