4.4 Article

Cortical Anoxic Spreading Depolarization During Cardiac Arrest is Associated with Remote Effects on Peripheral Blood Pressure and Postresuscitation Neurological Outcome

Journal

NEUROCRITICAL CARE
Volume 37, Issue SUPPL 1, Pages 139-154

Publisher

HUMANA PRESS INC
DOI: 10.1007/s12028-022-01530-2

Keywords

Cortical spreading depolarization; Anoxic spreading depolarization; Spreading ischemia; Neurovascular coupling; Cardiac arrest; Peripheral hemodynamics; Cerebral hemodynamics

Funding

  1. Arnold and Mabel Beckman Foundation
  2. Roneet Carmell Memorial Endowment Fund
  3. US National Institutes of Health [P41EB015890]
  4. National Science Foundation Graduate Research Fellowship Program [DGE-1321846]
  5. National Center for Advancing Translational Sciences of the National Institutes of Health [TL1TR001415-01, R21 EB024793]
  6. Institute of Clinical Translational Sciences'Clinical Translational Sciences Award (ICTS/CTSA) pilot grant [UL1 TR001414]
  7. National Center for Research Resources

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This study explored the role of anoxic spreading depolarizations (SD) in cerebral hemodynamics and metabolism, peripheral blood pressure, and the relationship between these variables in rats. The results showed decoupling of peripheral blood pressure from cerebral blood flow and metabolism during anoxic SD, possible modification of cerebrovascular resistance by anoxic SD, and a correlation between shorter time differences between anoxic SDs and better neurological outcomes.
Background Spreading depolarizations (SDs) are self-propagating waves of neuronal and glial depolarizations often seen in neurological conditions in both humans and animal models. Because SD is thought to worsen neurological injury, the role of SD in a variety of cerebral insults has garnered significant investigation. Anoxic SD is a type of SD that occurs because of anoxia or asphyxia. Although asphyxia leading to a severe drop in blood pressure may affect cerebral hemodynamics and is widely known to cause anoxic SD, the effect of anoxic SD on peripheral blood pressure in the extremities has not been investigated. This relationship is especially important to understand for conditions such as circulatory shock and cardiac arrest that directly affect both peripheral and cerebral perfusion in addition to producing anoxic SD in the brain. Methods In this study, we used a rat model of asphyxial cardiac arrest to investigate the role of anoxic SD on cerebral hemodynamics and metabolism, peripheral blood pressure, and the relationship between these variables in 8- to 12-week-old male rats. We incorporated a multimodal monitoring platform measuring cortical direct current simultaneously with optical imaging. Results We found that during anoxic SD, there is decoupling of peripheral blood pressure from cerebral blood flow and metabolism. We also observed that anoxic SD may modify cerebrovascular resistance. Furthermore, shorter time difference between anoxic SDs measured at different locations in the same rat was associated with better neurological outcome on the basis of the recovery of electrocorticography activity (bursting) immediately post resuscitation and the neurological deficit scale score 24 h post resuscitation. Conclusions To our knowledge, this is the first study to quantify the relationship between peripheral blood pressure, cerebral hemodynamics and metabolism, and neurological outcome in anoxic SD. These results indicate that the characteristics of SD may not be limited to cerebral hemodynamics and metabolism but rather may also encompass changes in peripheral blood flow, possibly through a brain-heart connection, providing new insights into the role of anoxic SD in global ischemia and recovery.

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