Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model

Abstract

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.

Retracted: microRNA‐129‐5p involved in the neuroprotective effect of dexmedetomidine on hypoxic‐ischemic brain injury by targeting COL3A1 through the Wnt/β‐catenin signaling pathway in neonatal rats

“…26 It after cardiac arrest is a leading reason for long-term neurologic disability and mortality in survivors and its pathophysiology encompasses a various cascade that can culminate in neuronal cell death and secondary brain injury. 27 Thus, in this study, we were supposed to explore the role of miR-129-5p in neuroprotective effect of DEX on HIBI by targeting COL3A1 through the Wnt/β-catenin signaling pathway in neonatal rats. Initially, our study revealed that the DEX + XAV-939 and DEX + miR-129-5p mimics groups had elevated weight, active avoidance rate, correct reaction rate, and weight rate of cerebral hemisphere (left/right), but decreased death rate, total reaction frequency and time, and water content of left cerebral hemisphere as compared with the DEX, DEX + NC and DEX + miR-129-5p inhibitors + XAV-939 groups.…”

Targeted therapeutic mild hypercapnia after cardiac arrest: a part of the bundle of care for mitigating secondary injury after cardiac arrest

“…These two previous studies [1,2] underlined the importance of preventing secondary cerebral injury after cardiac arrest and the role of arterial carbon dioxide on cerebral blood flow modulation in this. As described by Adrie and colleagues [3], cardiac arrest and sepsis have physiopathological similarities, including similar therapeutic interventions.…”

“…In the July 31 issue of Critical Care, Eastwood and colleagues [1] discussed the discordant results of the potential therapeutic role of mild hypercapnia in the early post-resuscitation period observed by Sekhon and colleagues [2].…”

“…For the management of septic shock, one major prognostic factor is the early initiation of appropriate treatments [4]. As underlined by Sekhon and colleagues [2], the negative results from randomized control trials of single physiological interventions (targeted temperature management and transfusion) aiming to avoid secondary injury after cardiac arrest are probably due to pathophysiological heterogeneity. Beyond this heterogeneity, we believe that, like in sepsis management, at a population scale, the benefit of a bundle of care including targeted therapeutic mild hypercapnia will be greater than a single intervention as described by Scheer and colleagues [5].…”

Targeted Temperature Management for Survivors of Sudden Cardiac Arrest

“…SCA frequently leads to prolonged hospitalization and is highly fatal with a mortality rate of approximately 90%. The leading cause of morbidity and mortality in SCA is profound neurologic injury, primarily due to lack of cerebral circulation during the arrest period, followed by secondary insults such as cerebral edema, reperfusion injury and hyperthermia [2]. SCA most commonly occurs outside of the hospital where mortality is significantly worse than in patients who suffer SCA inside a hospital [1,3].…”