(G-248) Native Pig Neurophysiological Activity Preservation Under Isolated Extracorporeal Pulsatile Perfusion Control

Introduction::

The study of neurovascular properties has been historically constrained by the systemic influences of various organs throughout the body. This systemic interplay presents a significant challenge, particularly when introducing independent variables for pharmacological interventions or metabolic tracing analysis. The resulting neural property characterization often becomes susceptible to organ-specific confounds. This paper presents an approach that addresses these limitations, offering a novel method for achieving selective vascular access to the brain and thereby facilitating more precise and controlled neurovascular studies. Our team has developed an innovative method and system, known as Extracorporeal Pulsatile Circulatory Control (EPCC). This method involves the use of software-controlled system to isolate perfusion to the brain, thereby creating a closed-loop access to the brain while maintaining normative physiology. One of the unique features of our approach is the preservation of physiologically relevant pulsatility, a critical factor often lacking in commercial perfusion machines. This feature is crucial as the absence of pulsatility has been linked to the abolishment of high-order neuronal activity, cerebral oxygenation, and vascular signaling. The EPCC system has successfully maintained native-like vascular pressure, flow, and pulsatile waveforms characteristic of subject-specific physiology. We have confirmed the viability of the brain through continuous electrocorticography and brain depth recordings, which yielded nearly identical values under both isolated and native circulation. This approach, which allows for complete independence in circulation and native-like physiology, opens up new possibilities for neurovascular experimentation, offering a significant advancement in the field of neuroscience.

Materials and Methods:: The brachiocephalic artery isolation procedure was conducted in a pig subject. Prior to initiation of isolated bypass, two 2F pressure catheters are placed in the brachiocephalic artery and right common carotid artery accordingly. Additionally, a perivascular flow probe is incorporated around the brachiocephalic artery to evaluate flow. Native physiological recordings are initiated and utilized for comparative analysis. A single waveform is isolated from the Native Brachiocephalic Pressure recording dataset and utilized as an input for control of Extracorporeal Pulsatile Circulatory Control (EPCC).

To initiate surgical isolation, the aorta was cannulated with an 8 French fenestrated arterial cannula near the origin of the brachiocephalic trunk. A venous straight cannula was secured in the superior vena cava. The ascending aorta was clamped proximal to the brachiocephalic trunk's origin and in the transverse arch between the brachiocephalic trunk and left subclavian artery, preventing flow to the left subclavian artery and lower extremities. Both subclavian arteries were occluded distal to the vertebral arteries' origin.

Following stable cardiopulmonary bypass initiation under normative continuous flow, custom generated pulsatile flow was initiated. The native pressure waveform and BPM were used as an input into a custom LabVIEW program to initiate EPCC. Carotid pressure, brachiocephalic pressure, flow, and pump motor performance were collected through the LabVIEW interface and stored for subsequent analysis. Any overt blood loss was compensated via supplementation of heterologous blood using the venous reservoir. The maximum EPCC duration was 5 hours.

Results, Conclusions, and Discussions::

Our study demonstrated that Extracorporeal Pulsatile Circulatory Control (EPCC) can faithfully replicate native waveforms. The comparative analysis between native and EPCC pressure and flow showed minimal fluctuations from native readings. Under EPCC, using an input native brachiocephalic pressure waveform with a heart rate of approximately 75 BPM, an adjusted systolic/diastolic ratio of 91.0/55.3 mmHg and a Mean Arterial Pressure (MAP) of 67.2 mmHg, the output isolated brachiocephalic pressure recordings had a systolic to diastolic pressure ratio of 95.8/59.7 mmHg, achieving a representative MAP of 71.7 mmHg. Accordingly, the corresponding native carotid pressure ratio was 86.9/56.8 mmHg, with a MAP of 66.8 mmHg. Brachiocephalic isolation resulted in an isolated carotid systolic to diastolic pressure ratio of 85.0/55.9 mmHg, with a target MAP of 65.6 mmHg. Lastly, comparative analysis of flow provided a native to isolated ratio of 6.224/9.011 ml/beat.
The brachiocephalic approach, in particular, showed limited pressure dampening between the arterial cannulation site and the common carotid artery. This suggests that the brachiocephalic approach is successful for maintaining almost identical systolic/diastolic pressure to native conditions as a result of direct vascular access under EPCC.
Cerebral activity under EPCC was preserved without interruption. The electrocorticography and depth electrode recordings showed little to no change in absolute power across the range of frequencies over the course of isolated interval recordings. Physiologic intracerebral pressure and temperature were also maintained. However, tissue oxygenation was greater than in native conditions, likely due to supplemental oxygen administration.
In conclusion, our study shows that EPCC can maintain near-native levels of cerebral physiological parameters and preserve cerebral activity over extended periods. This approach could be beneficial for investigating cellular signaling and other mechanisms likely to be perturbed under linear flow conditions.

Acknowledgements (Optional): : Our PCT Patent Application #PCT/US23/69013 was filed in June 2023.This project was funded by UT Southwestern funds (JMP). The figures and text associated with this application have been submitted to Nature's Scientific Reports for consideration of publication and is currently under review.

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