Quantitative assessment of the central versus peripheral effect of intravenous clonidine using baroreflex equilibrium diagrams

Clonidine is a first-generation central antihypertensive that reduces sympathetic nerve activity (SNA). Although clonidine also exerts peripheral vasoconstriction, the extent to which this vasoconstriction offsets the centrally mediated arterial pressure (AP)-lowering effect remains unknown. In anesthetized rats (n = 8), we examined SNA and AP responses to stepwise changes in carotid sinus pressure under control conditions and after intravenous low-dose (2 μg/kg) and high-dose clonidine (5 μg/kg). In the baroreflex equilibrium diagram analysis, the operating-point AP under the control condition was 115.2 (108.5–127.7) mmHg [median (25th–75th percentile range)]. While the operating-point AP after low-dose clonidine was not significantly different with or without the peripheral effect, the operating-point AP after high-dose clonidine was higher with the peripheral effect than without [81.3 (76.2–98.2) mmHg vs. 70.7 (57.7–96.9), P < 0.05]. The vasoconstrictive effect of clonidine partly offset the centrally mediated AP-lowering effect after high-dose administration.

Post-traumatic temporal bone pneumatocele presenting after aggressive Valsalva

We report a case of a temporal bone pneumatocele with full-thickness erosion of the cranium associated with aggressive nose blowing. This condition presented 9 years after traumatic fracture of the temporal bone. There are 17 reported cases of mastoid sinus hyperpneumatisation in the literature. Eleven of the 17 are associated with Valsalva manoeuvres or elevated middle ear pressure. However, no other cases of full-thickness erosion at the site of a former fracture have been reported. We propose that the fracture, in combination with elevated mastoid sinus pressure from aggressive nose blowing, led to escape and trapping of pressurised air in the epidural and subcutaneous spaces, which resulted in bone erosion.

The relationship between cerebral blood flow and venous sinus pressure: can hyperemia induce idiopathic intracranial hypertension?

Background It has been shown that idiopathic intracranial hypertension (IIH) in children is associated with cerebral hyperemia, which induces an increase in cerebral venous pressure. The current literature suggests venous pressure scales with blood flow in a linear fashion, however, a linear relationship would not raise the pressure high enough to induce IIH. There is, however, some evidence to suggest that this relationship could be quadratic in nature. The purpose of this paper is to characterize the relationship between cerebral blood flow and the pressure drop across the cerebral venous system. Methods 10 CT venogram data sets were collected for this study, with 5 useable geometries created. Computational fluid dynamics (CFD) models were generated using these geometries, with 10 simulations conducted per patient. The flow rates tested ranged from 200 mL/min to 2000 mL/min. 3D pressure and velocity streamline distributions were created and analyzed for each CFD model, with pressure drops across the cerebral venous system determined. The effective and hydraulic diameters were determined at the superior sagittal sinus, transverse sinus and both proximal and distal sigmoid sinuses. Results A quadratic relationship between blood flow and sinus pressure was found, with correlations of 0.99 or above in all five patients. The presence of vortical blood flow was found to explain this trend, with fluid curl and pressure drop correlations being above 0.97. This suggests that the presence of high blood flow should be considered in the diagnostic workup of IIH. Conclusions The cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops.

The incidence of obesity, venous sinus stenosis and cerebral hyperaemia in children referred for MRI to rule out idiopathic intracranial hypertension at a tertiary referral hospital: a 10 year review

Background Children referred to a tertiary hospital for the indication, “rule out idiopathic intracranial hypertension (IIH)” may have an increased risk of raised venous sinus pressure. An increase in sinus pressure could be due to obesity, venous outflow stenosis or cerebral hyperemia. The purpose of this paper is to define the incidence of each of these variables in these children. Methods Following a data base review, 42 children between the ages of 3 and 15 years were found to have been referred over a 10 year period. The body mass index was assessed. The cross sectional areas and circumferences of the venous sinuses were measured at 4 levels to calculate the hydraulic and effective diameters. The arterial inflow, sagittal and straight sinus outflows were measured. Automatic cerebral volumetry allowed the brain volume and cerebral blood flow (CBF) to be calculated. The optic nerve sheath diameter was used as a surrogate marker of raised intracranial pressure (ICP). The sagittal sinus percentage venous return was used as a surrogate marker of elevated venous pressure. Age and sex matched control groups were used for comparison. Results Compared to controls, the obesity rates were not significantly different in this cohort. Compared to controls, those at risk for IIH had a 17% reduction in transverse sinus and 14% reduction in sigmoid sinus effective cross sectional area (p = 0.005 and 0.0009). Compared to controls, the patients at risk for IIH had an arterial inflow increased by 34% (p < 0.0001) with a 9% larger brain volume (p = 0.02) giving an increase in CBF of 22% (p = 0.005). The sagittal and straight sinus venous return were reduced by 11% and 4% respectively (p < 0.0001 and 0.0009) suggesting raised venous sinus pressure. Forty five percent of the patients were classified as hyperemic and these had optic nerve sheath diameters 17% larger than controls (p < 0.0002) suggesting raised ICP. Conclusion In children with the chronic headache/ IIH spectrum, the highest associations were with cerebral hyperemia and mild venous sinus stenosis. Obesity was not significantly different in this cohort. There is evidence to suggest hyperemia increases the venous sinus pressure and ICP.

A murine model of increased coronary sinus pressure induces myocardial edema with cardiac lymphatic dilation and fibrosis

Myocardial edema is a consequence of many cardiovascular stressors, including myocardial infarction, cardiac bypass surgery, and hypertension. The aim of this study was to establish a murine model of myocardial edema and elucidate the response of cardiac lymphatics and the myocardium. Myocardial edema without infarction was induced in mice by cauterizing the coronary sinus, increasing pressure in the coronary venous system, and inducing myocardial edema. In male mice, there was rapid development of edema 3 h following coronary sinus cauterization (CSC), with associated dilation of cardiac lymphatics. By 24 h, males displayed significant cardiovascular contractile dysfunction. In contrast, female mice exhibited a temporal delay in the formation of myocardial edema, with onset of cardiovascular dysfunction by 24 h. Furthermore, myocardial edema induced a ring of fibrosis around the epicardial surface of the left ventricle in both sexes that included fibroblasts, immune cells, and increased lymphatics. Interestingly, the pattern of fibrosis and the cells that make up the fibrotic epicardial ring differ between sexes. We conclude that a novel surgical model of myocardial edema without infarct was established in mice. Cardiac lymphatics compensated by exhibiting both an acute dilatory and chronic growth response. Transient myocardial edema was sufficient to induce a robust epicardial fibrotic and inflammatory response, with distinct sex differences, which underscores the sex-dependent differences that exist in cardiac vascular physiology. NEW & NOTEWORTHY Myocardial edema is a consequence of many cardiovascular stressors, including myocardial infarction, cardiac bypass surgery, and high blood pressure. Cardiac lymphatics regulate interstitial fluid balance and, in a myocardial infarction model, have been shown to be therapeutically targetable by increasing heart function. Cardiac lymphatics have only rarely been studied in a noninfarct setting in the heart, and so we characterized the first murine model of increased coronary sinus pressure to induce myocardial edema, demonstrating distinct sex differences in the response to myocardial edema. The temporal pattern of myocardial edema induction and resolution is different between males and females, underscoring sex-dependent differences in the response to myocardial edema. This model provides an important platform for future research in cardiovascular and lymphatic fields with the potential to develop therapeutic interventions for many common cardiovascular diseases.

Changes in mean arterial pressure and end-tidal carbon dioxide content affect venous sinus pressures in patients with idiopathic intracranial hypertension: a randomized study

IntroductionLittle is known about how changes in physiologic parameters affect venous sinus pressure measurements, waveforms, or gradients associated with sinus stenosis.ObjectiveTo evaluate the effect of changes in cardiovascular and respiratory physiologic parameters on venous sinus pressure and caliber measurements in patients with idiopathic intracranial hypertension (IIH) undergoing venous sinus stenting.MethodsIn a prospective, randomized pilot study, eight patients with IIH undergoing venous sinus stenting were randomized to one of two groups. Under general anesthesia, patients underwent venous manometry and waveform recordings twice in succession based on assigned physiologic groups immediately before stenting. The mean arterial pressure (MAP) group maintained normocapnia but modified MAPs in two arms to control for temporal confounding: group A1 (MAP 60-80 mm Hg then 100–110 mm Hg) and group A2 (MAP 100-110 mm Hg then 60–80 mm Hg). The end-tidal carbon dioxide (EtCO2) group maintained a high-normal MAP similar to standard neuroanesthesia goals and modified EtCO2: group B1 (EtCO2 24–26 mm Hg then 38–40 mm Hg) and B2 (EtCO2 28–40 mm Hg then 24–26 mm Hg).ResultsIn group A, superior sagittal sinus (SSS) pressures (ranging from 8 to 76 mm Hg) and trans-stenotic pressure gradients (TSPGs) (ranging from 2 to 67 mm Hg) were seen at MAP of 100–110 mm Hg compared with SSS pressures (4–38 mm Hg) and TSPGs (3–31 mm Hg) at 60–80 mm Hg. In group B, SSS pressures and TSPGs were considerably higher at EtCO2 levels of 38–40 mm Hg (15–57 mm Hg and 3–44 mm Hg, respectively) than at 24–26 mm Hg (8–26 mm Hg and 1–8 mm Hg, respectively).ConclusionsDespite the small sample size, this pilot study demonstrates a dramatic effect of both MAP and EtCO2 on venous sinus pressures obtained during venography. These findings underscore the importance of maintaining normal physiologic cardiovascular and respiratory parameters during venous sinus manometry.

Coupling of CSF and sagittal sinus pressure in adult patients with pseudotumour cerebri

Objective Pseudotumour cerebri syndrome (PTCS including idiopathic intracranial hypertension) is characterised by the symptoms and signs of raised cerebrospinal fluid pressure (CSFp) in the absence of ventricular dilatation or an intracranial mass lesion. Its aetiology is unknown in the majority of cases but there is much evidence for impaired CSF absorption. Traditionally, sagittal sinus pressure has been considered to be independent of CSF pressure in adults. However, the discovery of stenoses of intracranial venous sinuses and introduction of venous sinus stenting has highlighted the importance of the venous drainage in PTCS. In this study, we have explored the relationship between CSFp and SSp before and during a CSF infusion test and during CSF drainage. Materials and methods Ten patients (9 females:1 male) with PTCS underwent infusion studies in parallel with direct retrograde cerebral venography. Both SSp and CSFp were recorded at a baseline and during CSFp elevation in a course of a CSF infusion test. The drainage of CSF after the CSF infusion was performed in 7 patients. In 5 cases, jugular venous pressure was also measured. Results CSFp and SSp including their amplitudes correlated significantly and strongly both at baseline (R = 0.96; p = 0.001) and during infusion (R = 0.92; p = 0.0026). During drainage, this correlation was maintained until SSp reached a stable value, whereas CSFp continued to decrease. Conclusions In this series of ten patients with PTCS, CSFp and SSp were coupled, both at baseline and during infusion. The implications of such coupling for the calculation of CSF outflow resistance are discussed.

Contrasting open-loop dynamic characteristics of sympathetic and vagal systems during baroreflex-mediated heart rate control in rats

Although heart rate (HR) is governed by the sympathetic and parasympathetic nervous systems, a head-to-head comparison of the open-loop dynamic characteristics of the total arc from a baroreceptor pressure input to the HR response has yet to be performed. We estimated the transfer function from carotid sinus pressure input to the HR response ( HCSP→HR) before and after bilateral vagotomy ( n = 7) as well as before and after the administration of a β-blocker propranolol ( n = 8) in anesthetized male Wistar-Kyoto rats. The carotid sinus pressure was perturbed according to a Gaussian white noise signal so that the input power spectra were relatively flat between 0.01 and 1 Hz. The gain plot of HCSP→HR was V-shaped. Vagotomy reduced the dynamic gain at 1 Hz (0.0598 ± 0.0065 to 0.0025 ± 0.0004 beats·min−1·mmHg−1, P < 0.001) but not at 0.01 or 0.1 Hz. β-Blockade reduced the dynamic gain at 0.01 Hz (0.247 ± 0.069 to 0.077 ± 0.017 beats·min−1·mmHg−1, P = 0.020) but not at 0.1 or 1 Hz. We also estimated the efferent limb transfer function from electrical vagal efferent stimulation to the HR response ( HVN→HR) under β-blockade conditions. We associated the model parameters of HVN→HR with the mean HR and the standard deviation of HR so that HVN→HR could be estimated based only on the HR data. We finally estimated the neural arc transfer function from a pressure input to efferent vagal nerve activity by dividing HCSP→HR by HVN→HR. The mathematically determined vagal neural arc showed derivative characteristics with its phase near zero radians at the lowest frequency.