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Hyperdynamic Spatiotemporal Cerebral Dynamics in Response to Cardiac Arrest and Resuscitation

Creative Commons 'BY' version 4.0 license

Annually, over 550,000 people in the United States suffer cardiac arrest (CA) and initial survival rates remain low (10-30%). Approximately 85 to 90% of survivors have impaired cognitive function, which leads to decreased quality of life for survivors, increased burden on caregivers, and direct costs of over $6 billion/year. To improve neurological recovery and understand how the brain recovers following CA, a critical need exists to investigate physiological processes that impact the brain. In collaboration with Dr. Yama Akbari’s lab, we developed a multi-modal platform with high temporal (10s of milliseconds) and spatial (~50µm) resolution. The platform combined laser speckle imaging (LSI), arterial blood pressure (ABP), and electroencephalography (EEG) to monitor cerebral blood flow (CBF), peripheral blood pressure, and brain electrophysiology, respectively. We applied this platform to an asphyxial CA and resuscitation preclinical model established in Dr. Akbari’s lab and characterized the hyperdynamic spatiotemporal cerebral dynamics that occur before, during, and after asphyxial CA and resuscitation.

The beginning of neurological recovery post-CA is the moment at which brain electrical activity resumes. We assessed the temporal evolution of CBF prior to this time point, and found two distinct CBF phases. The first phase is a hyperemic (increase in CBF) period that occurs 5-10min after resuscitation, which is followed by a period of prolonged, stabilized hypoperfusion (decrease in CBF). We found that brain electrical activity resumes after the CBF hyperemic period, but before CBF stabilizes hypoperfused. CBF and MAP data were then used to develop an empirical model to predict when brain electrical activity resumes to within 10% accuracy. The link between hemodynamics and the resumption of brain electrical activity, suggests that clinicians may be able to utilize and develop hemodynamic-altering therapeutics that modify the beginning of neurological recovery.

Next, we analyzed pulsatile CBF and femoral ABP waveforms in response to CA and resuscitation. Pulsatile blood flow is important due to its impact on oxygen uptake, vascular tone, and cellular metabolism. Our study revealed that CBF pulsatility is altered significantly from baseline within 2h after resuscitation, but ABP pulsatility changes little. Interestingly, ABP pulsatility and not CBF pulsatility correlates with short-term neurological outcome. These results suggest that simultaneous monitoring of CBF and ABP pulsatility is necessary, and therapeutic modulation of pulsatility post-CA may lead to changes in neurological outcome.

Lastly, we analyzed spatiotemporal CBF changes during three hyperdynamic periods: (1) entering CA, (2) within 5min after resuscitation, and (3) from hyperemia to hypoperfusion (i.e., 5 to 20min after resuscitation). Spreading CBF waves were visualized during each phase. We found that an increase in total CBF prior to the onset of spreading wave (1) was associated with worse neurological outcome, waves (1) and (3) propagated in opposite directions, and waves (2) and (3) resembled a well-known phenomenon called cortical spreading depression. These spatiotemporal characteristics are complex, yet may have clinical importance to neurological outcome.

Collectively, these findings highlight the complex nature of the hyperdynamic cerebral response to CA and resuscitation. The multi-modal platform and results suggest a novel therapeutic approach involving modulation of hemodynamics during hyperdynamic periods of CA may improve neurological outcome.

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