Brain Protection after Anoxic Brain Injury: Is Lactate Supplementation Helpful?

Filippo Annoni,Lorenzo Peluso,Elisa Gouvêa Bogossian,Jacques Creteur,Fabio Silvio Taccone,Elisa R Zanier

doi:10.3390/cells10071714

Filippo Annoni, Lorenzo Peluso + Show 4 more

Open Access

https://doi.org/10.3390/cells10071714

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Abstract

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest.

Highlights

Sudden cardiac arrest (CA) is characterized by the abrupt loss of heart function and organs perfusion and is the third leading cause of death in Europe [1,2,3,4]
Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism
We addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest

Summary

Background

Sudden cardiac arrest (CA) is characterized by the abrupt loss of heart function and organs perfusion and is the third leading cause of death in Europe [1,2,3,4]. While acute/chronic coronary disease is the main cause of CA, extended brain damage remains the most important determinant of poor outcome in resuscitated CA patients [5]. With the loss of perfusion pressure, the whole body is exposed to an ischemic injury for a variable amount of time and, eventually, to massive and sudden reperfusion when resuscitation is achieved. The brain consumes more than 25% of all available circulating glucose and 20% of oxygen, despite it representing only 2% of total body weight [7,8], and the metabolic cost of its development characterizes our species [9]. Finding new therapeutic options is a priority in clinical research

Mechanisms Involved in Brain Injury after Resuscitation from Cardiac Arrest

Lactate as Alternative Energetic Substrate

Lactate Enriched Solutions in Traumatic Brain Injury

Findings

Conclusions and Future Perspectives