Mitochondrial dysfunction in fatal ventricular arrhythmias

Abstract

Ventricular fibrillation (VF) and sudden cardiac arrest (SCA) remain some of the most important public health concerns worldwide. For the past 50 years, the recommendation in the Advanced Cardiac Life Support (ACLS) guidelines has been that defibrillation is the only option for shockable cardiac arrest. There is growing evidence to demonstrate that mitochondria play a vital role in the outcome of postresuscitation cardiac function. Although targeting mitochondria to improve resuscitation outcome following cardiac arrest has been proposed for many years, understanding concerning the changes in mitochondria during cardiac arrest, especially in the case of VF, is still limited. In addition, despite new research initiatives and improved medical technology, the overall survival rates of patients with SCA still remain the same. Understanding cardiac mitochondrial alterations during fatal arrhythmias may help to enable the formulation of strategies to improve the outcomes of resuscitation. The attenuation of cardiac mitochondrial dysfunction during VF through pharmacological intervention as well as ischaemic postconditioning could also be a promising target for intervention and inform a new paradigm of treatments. In this review, the existing evidence available from in vitro, ex vivo and in vivo studies regarding the roles of mitochondrial dysfunction during VF is comprehensively summarized and discussed. In addition, the effects of interventions targeting cardiac mitochondria during fatal ventricular arrhythmias are presented. Since there are no clinical reports from studies targeting mitochondria to improve resuscitation outcome available, this review will provide important information to encourage further investigations in a clinical setting.

Association between Intra-Arrest Blood Glucose Level and Outcomes of Resuscitation at the Emergency Department: A Retrospective Study

“…Cardiac arrest, recognized as major stress, causes severe metabolic derangements and global ischemia/reperfusion (IR) injury [ 25 ]. The connections between cardiac IR injury, fatal ventricular arrhythmias, and cardiac arrest have been well established across preclinical and clinical studies [ 30 , 31 ]. These links also affect the endocrine glands, including the pancreas, and possibly lead to reduced hormonal synthesis, resulting in lower insulin and glucagon-like peptide 1 (GLP-1) levels.…”

Association between calcium administration and outcomes during adult cardiopulmonary resuscitation at the emergency department

“…This study also demonstrated that calcium administration during cardiac arrest without certain indications is associated with unfavorable outcomes, possibly because of effects of reperfusion injury to the ischemic heart, brain, and other vital organs mediated by calcium. [ 29 ]…”

Mitochondria – More than just batteries for cellular function

“…Alterations in mitochondrial function are a hallmark of cardiac diseases such as ventricular arrhythmias, sudden cardiac arrest, and cardiomyopathies. Wongtanasarasin summarizes data from in vitro, in vivo, and ex vivo studies on rodents regarding mitochondrial alterations in ventricular arrhythmias 4 . During an ischaemic episode, when oxygen is temporarily not available, a switch to anaerobic glycolysis occurs, and lactic acid release lowers the cytosolic pH.…”

“…Wongtanasarasin summarizes data from in vitro, in vivo, and ex vivo studies on rodents regarding mitochondrial alterations in ventricular arrhythmias. 4 During an ischaemic episode, when oxygen is temporarily not available, a switch to anaerobic glycolysis occurs, and lactic acid release lowers the cytosolic pH. The switch from aerobic to anaerobic glycolysis is named the Warburg effect and is frequently found in cancer cells, too, although oxygen is available.…”