Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model

INTRODUCTION Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. METHODS An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between -13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived. RESULTS Strong correlations were observed between posture and: mean carotid/femoral arterial (r = - 0.97, r = - 0.87), intracranial, intrathecal (r = - 0.98, r = 0.94), jugular (r = - 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = - 0.83, r = 0.84, r = - 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of - 15.9 ± 6.0 dB/decade. CONCLUSIONS Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces

Venous dynamics in anesthetized sheep govern postural-induced changes in cerebrospinal fluid pressure comparable to those in humans

Sheep are popular large animals in which to model human disorders and to study physiological processes such as cerebrospinal fluid dynamics. However, little is known about vascular compensatory mechanisms affecting cerebrospinal fluid pressures during acute postural changes in sheep. Six female white Alpine sheep were anesthetized to investigate the interactions of the vascular and cerebrospinal fluid system by acquiring measurements of intracranial pressure and central and jugular venous pressure during passive postural changes induced by a tilt table. The cross-sectional area of the common jugular vein and venous blood flow velocity was recorded. Anesthetized sheep showed bi-phasic effects of postural changes on intracranial pressure during tilting. A marked collapse of the jugular vein was observed during head-over-body tilting; this is in accordance with findings in humans. Active regulatory effects of the arterial system on maintaining cerebral perfusion pressure were observed independent of tilting direction. Conclusion: Anesthetized sheep show venous dynamics in response to posture-induced changes in intracranial pressure that are comparable with those in humans

The Sheep as a Comprehensive Animal Model to Investigate Interdependent Physiological Pressure Propagation and Multiparameter Influence on Cerebrospinal Fluid Dynamics

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model

A Soft Robotic Actuator System for in vivo Modeling of Normal Pressure Hydrocephalus

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: In vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus

Insights of posture dependent pressure characteristics in five rats

Current shunt treatments of hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid (CSF) and intracranial pressure (ICP) fluctuations, suffer malfunctions caused by changes in patient’s posture. Research toward a quantitative model describing posture dependent dynamics of CSF related pressures such as ICP and blood pressure (BP) shall provide rele vant information that can lead to a better understanding of CSF dynamics and thus, improved treatment outcomes. In this pilot study, ICP and femoral blood pressure (FBP) were measured concurrently in anaesthetized as well as awake and freely moving rats using radio telemetry. It was shown that despite the inherent challenges of limited space for sensor implants and rapid movements leading to strong artefacts, influences on CSF related pressure fluctuations due to posture changes can be observed in individual rats.ISSN:2364-550

First insights of posture related pressure dynamics in awake and freely moving rats

Introduction: To improve outcomes of current shunt treatments for hydrocephalus, a better understanding of cerebrospinal fluid (CSF) physiology is needed. Because malfunctions arise from posture changes, measurements of intracranial pressure (ICP) fluctuations and their relation to blood pressure during these changes shall provide valuable insights. Methods: ICP and femoral blood pressure (FBP) of five healthy rats were continuously measured in a chronic trial via radio telemetry implants and sampled at 1 kHz. While being awake and moving freely in an observation box, the rats were monitored with a camera system at 30 fps. Means and correlation coefficients of ICP and FBP during ten natural rear ups per rat were analyzed with t-tests. Results: Rear ups lasted on average 2.13 s. During these, FBP assessed as mean±SD (106.5 ± 17.4 mmHg) and ICP (1.4 ± 3.8 mmHg) were on average lower than FBP (118.9 ± 11.9 mmHg) and ICP (1.6 ± 4.0 mmHg) before rear ups. Changes of FBP were significant (p < 0.05) in all rats, whereas changes in ICP were significant (p < 0.05) in only two rats. In one of these two rats, correlation coefficients were significant (p < 0.01). ICP and FBP during these rear ups were on average moderately positively correlated (r = 0.24). Conclusion: Concurrent measurements of CSF related pressures in rats are inherently challenging due to the limited space for sensor implants and rapid movements leading to strong artefacts. However, statistically significant CSF dynamics due to posture changes could be observed using high resolution pressure and video recordings.ISSN:2045-811

Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model

Introduction Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. Methods An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between –13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived. Results Strong correlations were observed between posture and: mean carotid/femoral arterial (r = − 0.97, r = − 0.87), intracranial, intrathecal (r = −0.98, r = 0.94), jugular (r = − 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = − 0.83, r = 0.84, r = − 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of − 15.9 ± 6.0 dB/decade. Conclusions Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.ISSN:2045-811

Venous dynamics in anesthetized sheep govern postural‐induced changes in cerebrospinal fluid pressure comparable to those in humans

Abstract Sheep are popular large animals in which to model human disorders and to study physiological processes such as cerebrospinal fluid dynamics. However, little is known about vascular compensatory mechanisms affecting cerebrospinal fluid pressures during acute postural changes in sheep. Six female white Alpine sheep were anesthetized to investigate the interactions of the vascular and cerebrospinal fluid system by acquiring measurements of intracranial pressure and central and jugular venous pressure during passive postural changes induced by a tilt table. The cross‐sectional area of the common jugular vein and venous blood flow velocity was recorded. Anesthetized sheep showed bi‐phasic effects of postural changes on intracranial pressure during tilting. A marked collapse of the jugular vein was observed during head‐over‐body tilting; this is in accordance with findings in humans. Active regulatory effects of the arterial system on maintaining cerebral perfusion pressure were observed independent of tilting direction. Conclusion: Anesthetized sheep show venous dynamics in response to posture‐induced changes in intracranial pressure that are comparable with those in humans

The Sheep as a Comprehensive Animal Model to Investigate Interdependent Physiological Pressure Propagation and Multiparameter Influence on Cerebrospinal Fluid Dynamics

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model.ISSN:1662-453XISSN:1662-454

Venous dynamics in anesthetized sheep govern postural‐induced changes in cerebrospinal fluid pressure comparable to those in humans

Sheep are popular large animals in which to model human disorders and to study physiological processes such as cerebrospinal fluid dynamics. However, little is known about vascular compensatory mechanisms affecting cerebrospinal fluid pressures during acute postural changes in sheep. Six female white Alpine sheep were anesthetized to investigate the interactions of the vascular and cerebrospinal fluid system by acquiring measurements of intracranial pressure and central and jugular venous pressure during passive postural changes induced by a tilt table. The cross-sectional area of the common jugular vein and venous blood flow velocity was recorded. Anesthetized sheep showed bi-phasic effects of postural changes on intracranial pressure during tilting. A marked collapse of the jugular vein was observed during head-over-body tilting; this is in accordance with findings in humans. Active regulatory effects of the arterial system on maintaining cerebral perfusion pressure were observed independent of tilting direction. Conclusion: Anesthetized sheep show venous dynamics in response to posture-induced changes in intracranial pressure that are comparable with those in humans.ISSN:2051-817