Prognostic Value of Plasma Mitochondrial DNA and Cytochrome C After Cardiac Arrest

Overview

The aim of the study is to determine prognostic value of plasma mitochondrial DNA and cytochrome C after cardiac arrest. The study will be conducted in three parts: 1. Determine plasma concentrations of mitochondrial DNA and cytochrome C in healthy population. 2. Determine release profile of mitochondrial DNA and cytochrome C to plasma after cardiac arrest. 3. Determine plasma prognostic value of mitochondrial DNA and cytochrome C after cardiac arrest and compare it with established prognostic methods.

Scientific background Cardiac arrest is one of leading causes of mortality in developed world. Survival ranges between 15 and 22%. Patients surviving cardiac arrest can have significant neurological impairment. None of currently available diagnostic methods can detect neurological consequences in early post resuscitation period. Biomarkers (NSE - neuron specific enolase, protein S100, GFAP - glial fibrillary acidic protein), imaging (computer tomography, magnetic resonance imaging) and functional studies (EEG - electro encephalography, SSEP - somatosensory evoked potentials) have all shown only limited prognostic value in predicting survival with good neurological outcome after cardiac arrest. Mitochondrial damage is one of key mechanisms of postresuscitation dysfunction. Elevated values of mitochondrial damage-associated molecular patterns were already linked to worst survival after cardiac arrest and critical illness. Mitochondrial damage often results in cell death and mitochondrial damage-associated molecular patterns are released into bloodstream. Mitochondrial damage-associated molecular patterns that can be detected in serum or plasma are: mitochondrial DNA, mitochondrial transcription factor A, N-formyl peptides, succinate, cardiolipin, cytochrome C... With a more sensitive method of early neuroprognostication after cardiac arrest the limited medical resources could be used more effectively in patients with chance of good neurological recovery. Aim of the study The aim of this study is to research the role of mitochondrial damage-associated molecular patterns in patients after cardiac arrest. 1. Determine normal plasma values of mitochondrial damage-associated molecular patterns in healthy population. 2. Compare current prognostic procedures of post-resuscitation neurological damage with prognostic value of mitochondrial DNA and cytochrome C in plasma. Expected results Due to central role of mitochondria in hypoxic-ischemic tissue damage a greater mitochondrial damage (measured trough release of mitochondrial damage-associated molecular patterns) is expected to have direct correlation with extent of tissue damage (also neurological). Currently published data indicate that patients with higher plasma mitochondrial DNA levels after cardiac arrest have higher mortality. Correlation of mitochondrial damage-associated molecular patterns to extent of neurological damage in survivors of cardiac arrest was not researched yet. Methods 1. Measurement of measure mitochondrial damage-associated molecular patterns in healthy population (mitochondrial DNA and cytochrome C). 2. Determination of releasing profile of mitochondrial DNA and cytochrome C in survivors of cardiac arrest and establishment of best sample collection time. 3. Calculation of predictive value for survival of cardiac arrest with good neurological outcome for mitochondrial DNA and cytochrome C. Mitochondrial damage-associated molecular patterns will be measured in samples of plasma. Mitochondrial DNA will be measured using PCR method. Cytochrome C will be measured using ELISA.

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