Casper Schwartz Riedel continues post.doc. work looking into cerebral hemodynamics in obstructive sleep apnea

Short project summary

Our research project seeks to elucidate the effects of obstructive sleep apnea (OSA) on cerebral hemodynamics, resulting in transient brain pressure spikes and possibly increased risks of stroke and cognitive decline. This will be investigated in a large animal model with invasive measurements and advanced MRI, and will be expanded to human MRI studies to track OSA-induced blood flow alterations.

Background

Sleep-disordered breathing (SDB), particularly OSA, is a prevalent condition associated with an increased risk of cardiovascular and cerebrovascular diseases. We recently found that OSA causes transient brain pressure spikes, a connection not fully recognized previously, and the underlying physiology remains unknown. Such mechanisms could explain the notable link between OSA and increased risks of stroke, cerebrovascular diseases, and possibly cognitive impairments in patients with OSA.

Aim

To explore this connection, we aim to conduct a translational study examining OSA physiology in a large animal model, apply these insights to human subjects, and fundamentally enhance our understanding of OSA pathophysiology, focusing on its influence on cerebral hemodynamics and brain pressure regulation.

Methods & Design

Changes in the cardiovascular system and brain pressure during OSA will be measured invasively in an established porcine OSA model. These changes will be assessed and validated by analyzing 4D MRI flow in the cerebral venous and arterial systems. The 4D MRI flow findings from the porcine model will subsequently be confirmed in both healthy human controls and patients with severe OSA.

Preliminary results

To verify the physiological association between OSA and transient brain pressure elevations, we conducted a proof-of-concept study with five animals in which apneas were simulated by applying negative intrathoracic pressure. This resulted in transient brain pressure elevations above 40 mmHg (baseline levels 7-15 mmHg), confirming the link between OSA and brain pressure changes we previously showed in humans, with a dose-dependent response with more negative intrathoracic pressure generating higher transient brain pressure elevations. The central venous pressure increased immediately before the transient brain pressure elevation in all simulated apneas.