Restoration of brain circulation and cellular functions hours post-mortem

Abstract

the BEx technology and the research described herein. Z.V. and S.G.D. developed the surgical procedure, performed the perfusion experiments, and collected and processed tissue samples for subsequent analyses; Z.V. and S.G.D. performed the MRI studies and analyzed the data;

Independent Functional Outcomes after Prolonged Coma following Cardiac Arrest: A Mechanistic Hypothesis

“…[5][6][7][8]10 However, our results strongly argue that favorable recoveries are possible even after several weeks of coma in a subset of patients. Better understanding of mechanisms of cellular functional recovery after exposure to anoxic conditions 71 will aid further uncovering of mechanisms of intrinsic neuronal protection strategies 24 and allow design of future clinical trials 72 that will identify more reliable biomarkers of recovery in patients with prolonged post-cardiac arrest coma.…”

Oxygen and brain death; back from the brink

“…Beyond limits; the unexpected resilience of the brain. The traditional notion that the mammalian brain is irreversibly damaged soon after blood stops circulating, owing to limited energy stores, has been challenged by two landmark studies in particular [(Vrselja et al., ; Dreier et al, ), both marked by a gold star], sparking widespread debate over the clinical diagnosis of brain death and organ transplantation. (a) Neuronal, electrophysiological and metabolic recovery has been observed after global cerebral ischaemia or after a prolonged post‐mortem interval in the animal brain.…”

“…(a) Neuronal, electrophysiological and metabolic recovery has been observed after global cerebral ischaemia or after a prolonged post‐mortem interval in the animal brain. The bottom panels (marked by a gold star), modified from (Vrselja et al., ), illustrate the cerebral metabolic rate for oxygen (CMRO 2 ) in 6‐ to 8‐month‐old pigs ( Sus scrofa domesticus , n = 4) for up to 6 h after a 4 h post‐mortem interval using a customized extracorporeal pulsatile‐perfusion system and haemoglobin‐based, acellular, non‐coagulative, echogenic, cytoprotective perfusate (‘Brain Ex ’), with arteriovenous gradients highlighting a remarkable resurgence of O 2 (and glucose; data not shown) consumption; colour Doppler flow data also highlight increased flow in the pericallosal artery after administration of nimodipine, an L‐type voltage‐gated calcium channel antagonist that increases cerebral perfusion, signifying retention of vascular dilatation. Abbreviations: L/R‐ICA, left/right internal carotid artery; NS, non‐significant ( P > 0.05); PG, pulse generator transforming continuous flow to pulsatile perfusion; and *significant ( P < 0.05) using Student's paired t tests.…”

“…Equally fascinating, the 'high-fliers' , including Ruppell's griffon, Gyps rueppellii, and the bar-headed goose, Anser indicus, have been observed at altitudes of 9000-11,278 m, with the former capable of achieving the high metabolic rates required for flapping flight and running even when exposed to a simulated P aO 2 equivalent to that encountered on F I G U R E 4 Beyond limits; the unexpected resilience of the brain. The traditional notion that the mammalian brain is irreversibly damaged soon after blood stops circulating, owing to limited energy stores, has been challenged by two landmark studies in particular [ (Vrselja et al, 2019;Dreier et al, 2018), both marked by a gold star], sparking widespread debate over the clinical diagnosis of brain death and organ transplantation. (a) Neuronal, electrophysiological and metabolic recovery has been observed after global cerebral ischaemia or after a prolonged post-mortem interval in the animal brain.…”

Palliative sedation and medical assistance in dying: Distinctly different or simply semantics?

“…Nevertheless, the ability to restore cellular function up to four hours after death is contrary to the previously held understanding that oxygen stores, global electrical activity, and, at least theoretically, consciousness cease after seconds of interrupted blood flow (Vrselja et al, 2019).…”