What is death?

“Just as birth certificates note the time we enter the world, death certificates mark the moment we exit it. This practice reflects traditional notions about life and death as binaries. We are here until, suddenly, like a light switched off, we are gone. 

But while this idea of death is pervasive, evidence is building that it is an outdated social construct, not really grounded in biology. Dying is in fact a process—one with no clear point demarcating the threshold across which someone cannot come back.”

*Nuwer, R. (2023). What is death? New neuroscience is challenging our understanding of the dying process—bringing opportunities for the living. MIT Technology Review.

See also —

*Andrijevic, D., Vrselja, Z., Lysyy, T., Zhang, S., Skarica, M., Spajic, A., Dellal, D., Thorn, S. L., Duckrow, R. B., Ma, S., Duy, P. Q., Isiktas, A. U., Liang, D., Li, M., Kim, S., Daniele, S. G., Banu, K., Perincheri, S., Menon, M. C., . . . Sestan, N. (2022). Cellular recovery after prolonged warm ischaemia of the whole body. Nature, 608(7922), 405-412. [PDF] [Cited by]

After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.”

*Parnia, S., Keshavarz Shirazi, T., Patel, J., Tran, L., Sinha, N., O’Neill, C., Roellke, E., Mengotto, A., Findlay, S., McBrine, M., Spiegel, R., Tarpey, T., Huppert, E., Jaffe, I., Gonzales, A. M., Xu, J., Koopman, E., Perkins, G. D., Vuylsteke, A., . . . Deakin, C. D. (2023). AWAreness during REsuscitation – II: A multi-center study of consciousness and awareness in cardiac arrest. Resuscitation, 191, 109903. [PDF] [Cited by]

“Introduction: Cognitive activity and awareness during cardiac arrest (CA) are reported but ill understood. This first of a kind study examined consciousness and its underlying electrocortical biomarkers during cardiopulmonary resuscitation (CPR).

Methods: In a prospective 25-site in-hospital study, we incorporated a) independent audiovisual testing of awareness, including explicit and implicit learning using a computer and headphones, with b) continuous real-time electroencephalography(EEG) and cerebral oxygenation(rSO2) monitoring into CPR during in-hospital CA (IHCA). Survivors underwent interviews to examine for recall of awareness and cognitive experiences. A complementary cross-sectional community CA study provided added insights regarding survivors’ experiences.

Results: Of 567 IHCA, 53(9.3%) survived, 28 of these (52.8%) completed interviews, and 11(39.3%) reported CA memories/perceptions suggestive of consciousness. Four categories of experiences emerged: 1) emergence from coma during CPR (CPR-induced consciousness [CPRIC]) 2/28(7.1%), or 2) in the post-resuscitation period 2/28(7.1%), 3) dream-like experiences 3/28(10.7%), 4) transcendent recalled experience of death (RED) 6/28(21.4%). In the cross-sectional arm, 126 community CA survivors’ experiences reinforced these categories and identified another: delusions (misattribution of medical events). Low survival limited the ability to examine for implicit learning. Nobody identified the visual image, 1/28(3.5%) identified the auditory stimulus. Despite marked cerebral ischemia (Mean rSO2 = 43%) normal EEG activity (delta, theta and alpha) consistent with consciousness emerged as long as 35–60 minutes into CPR.

Conclusions: Consciousness, awareness and cognitive processes may occur during CA. The emergence of normal EEG may reflect a resumption of a network-level of cognitive activity, and a biomarker of consciousness, lucidity and RED (authentic “near-death” experiences).”

*Vrselja, Z., Daniele, S. G., Silbereis, J., Talpo, F., Morozov, Y. M., Sousa, A. M. M., Tanaka, B. S., Skarica, M., Pletikos, M., Kaur, N., Zhuang, Z. W., Liu, Z., Alkawadri, R., Sinusas, A. J., Latham, S. R., Waxman, S. G., & Sestan, N. (2019). Restoration of brain circulation and cellular functions hours post-mortem. Nature, 568(7752), 336–343. [PDF] [Cited by]

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.”

Questions? Please let me know (engelk@grinnell.edu).