Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC)

Scientific Reports · 27 authors, 13 centres

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TL;DR

Researchers developed a method to surgically isolate and artificially control the blood flow to a pig's brain using a pulsatile pump, maintaining near-normal conditions for several hours. They found that key brain electrical activity and physiological parameters remained stable and similar to the native state, demonstrating the technique's potential for isolated brain studies.

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This preclinical study in pigs describes the development of extracorporeal pulsatile circulatory control (EPCC) to surgically isolate cerebral circulation from the systemic body. Using a computerized algorithm, the system maintained blood pressure, flow, and pulsatility at near-native values for up to 5 hours. Brain activity was continuously monitored via electrocorticography and depth electrodes. The central result was that electrocorticographic and deep brain recordings, along with cerebral oxygenation, pressure, temperature, and microscopic structure, remained unaltered or minimally perturbed under EPCC compared to native perfusion. Limitations include the 5-hour study duration, the need to estimate perfusion distribution between brain and non-brain head tissues, and the use of ketamine anesthesia. The findings suggest EPCC is a viable method for studying brain function and pharmacology in relative isolation from systemic influences.

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other

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preclinical research

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ORIGINAL PAPER

PMC10457326

Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC)

Scientific Reports

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ABSTRACT

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even while preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) was delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.

CITATION EXPORT

Muhammed Shariff, Aksharkumar Dobariya, Obada Albaghdadi et al.. Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC). Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-39344-7

AUTHORS

27 · 13 CENTRES

Muhammed Shariff, Aksharkumar Dobariya, Obada Albaghdadi, Jacob Awkal, Hadi Moussa, Gabriel Reyes, Mansur Syed, Robert Hart, Cameron Longfellow, Debra Douglass, Tarek Y. El Ahmadieh, Levi B. Good, Vikram Jakkamsetti, Gauri Kathote, Gus Angulo, Qian Ma, Ronnie Brown, Misha Dunbar, John M. Shelton, Bret M. Evers, Sourav Patnaik, Ulrike Hoffmann, Amy E. Hackmann, Bruce Mickey, Matthias Peltz, Michael E. Jessen, Juan M. Pascual

1https://ror.org/049emcs32grid.267323.10000 0001 2151 7939The Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Richardson, TX 75080 USA
2https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Rare Brain Disorders Program, Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Mail Code 8813, Dallas, TX 75390-8813 USA
3https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
4https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
5https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Animal Resource Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
6https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
7https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
8https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
9https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
10https://ror.org/05byvp690grid.267313.20000 0000 9482 7121Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
11grid.267313.20000 0000 9482 7121Eugene McDermott Center for Human Growth and Development/Center for Human Genetics, The University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
12grid.411390.e0000 0000 9340 4063Present Address: Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA 92354 USA
13https://ror.org/04b6nzv94grid.62560.370000 0004 0378 8294Present Address: Heart and Vascular Center Brigham and Women’s Hospital, Boston, MA 02115 USA