Changes in intrathoracic pressure, not arterial pulsations, exert the greatest effect on tracer influx in the spinal cord

Abstract

Background Cerebrospinal fluid (CSF) circulation in the brain has garnered considerable attention in recent times. In contrast, there have been fewer studies focused on the spine, despite the expected importance of CSF circulation in disorders specific to the spine, including syringomyelia. The driving forces that regulate spinal CSF flow are not well defined and are likely to be different to the brain given the anatomical differences and proximity to the heart and lungs. The aims of this study were to determine the effects of heart rate, blood pressure and respiration on the distribution of CSF tracers in the spinal subarachnoid space, as well as into the spinal cord interstitium. Methods In Sprague Dawley rats, physiological parameters were manipulated such that the effects of spontaneous breathing (generating alternating positive and negative intrathoracic pressures), mechanical ventilation (positive intrathoracic pressure only), tachy/bradycardia, as well as hyper/hypotension were separately studied. To investigate spinal CSF hydrodynamics, in vivo near-infrared imaging of intracisternally infused indocyanine green was performed. CSF tracer transport was further characterised with in vivo two-photon intravital imaging. Tracer influx at a microscopic level was quantitatively characterised by ex vivo epifluorescence imaging of fluorescent ovalbumin. Results Compared to mechanically ventilated controls, spontaneous breathing animals had significantly greater movement of tracer in the subarachnoid space. There was also greater influx into the spinal cord interstitium. Hypertension and tachycardia had no significant effect on spinal subarachnoid spinal CSF tracer flux and exerted less effect than respiration on tracer influx into the spinal cord. Conclusions Intrathoracic pressure changes that occur over the respiratory cycle, particularly decreased intrathoracic pressures generated during inspiration, have a profound effect on tracer movement after injection into spinal CSF and increase cord parenchymal tracer influx. Arterial pulsations likely drive fluid transport from perivascular spaces into the surrounding interstitium, but their overall impact is less than that of the respiratory cycle on net tracer influx.

Characterising spinal cerebrospinal fluid flow in the pig with phase-contrast magnetic resonance imaging

“…Mean arterial pressure is thought to in uence CSF ow in the cerebral perivascular spaces (48); however, its effect on pulsating spinal CSF ow in the SAS is understudied. In one rat study there was no effect of mean arterial pressure on spinal SAS CSF ow (40). In the current study, the animal that received a propofol bolus during the scan (P014; T11/T12 and L1/L2 scanned prior to bolus, and T8/T9 and C2/C3 after bolus) had abnormally higher peak systolic ow at T11/T12 and L1/L2 dorsally, T8/T9 and L1/L2 ventrally and peak diastolic ow at T8/T9 dorsally.…”

“…Although the relative contribution of respiratory and cardiac cycles to CSF dynamics is unclear, it is evident that physiological variations of both can alter CSF ow (40)(41)(42)(43). It is commonly thought that CSF travels cranially with inhalation, and caudally with exhalation, due to changes in intrathoracic pressure with spontaneous breathing (16,17,41,42).…”

“…Positive intrathoracic pressure throughout the respiratory cycle may contribute to lower CSF ow. Mechanically ventilated rats had less movement of uorescent tracer in the spinal SAS in the caudal direction compared to spontaneously breathing animals (40). This suggests that respiratory conditions need to be carefully considered in CSF ow study comparisons.…”

“…It is apparent that reduced arterial pulse pressure decreases CSF ow in the spinal perivascular spaces (45,46), but its effect on CSF pulsations in the SAS is unknown. There is limited and con icting evidence that heart rate in uences CSF ow: increasing heart rate resulted in increased bidirectional CSF ow velocities in a three dimensional computational uid dynamics model of the SAS (43), while a study in rats showed that increased heart rate had little in uence on CSF ow (40). The heart rate range in this study (71-174 bpm) is larger than in the other animal studies (canines, 70 − 110 bpm; NHP, 92-132 bpm).…”

Characterising spinal cerebrospinal fluid flow in the pig with phase-contrast magnetic resonance imaging

“…Positive intrathoracic pressure throughout the respiratory cycle may contribute to lower CSF flow. Mechanically ventilated rats had less movement of fluorescent tracer in the spinal SAS in the caudal direction compared to spontaneously breathing animals [ 54 ]. This suggests that respiratory conditions need to be carefully considered in CSF flow study comparisons.…”