Abstract
ABSTRACTSudden cardiac death (SCD) is the leading cause of death worldwide. Myocardial ischemia (MI) is the most common underlying causal disorder for SCD. Metabolic risks leading to SCD during acute MI are still not fully understood. Here, using tissue metabolomics, we aimed to investigate myocardial metabolic alterations relevant to SCD events in an acute MI rat model induced by coronary artery ligation (CAL). Thirty-four rats were successfully performed CAL, of which 13 developed lethal ventricular tachyarrhythmia (LVTA)-SCD and 7 developed severe atrioventricular block (AB)-SCD. Fourteen rats that survived within 70 min after the ligation were served as peer controls. The partial least squares-discriminant analysis plots demonstrated clear separations between the SCD rats and controls, indicating obvious differences in myocardial metabolome between these rats. The levels of isoleucine, lactate, glutamate choline, phosphorylcholine, taurine and asparagine in ischemic myocardia were positively associated with LVTA-SCD events; in contrast, the levels of alanine, urea, phenylalanine, linoleic acid, elaidic acid and stearic acid were inversely correlated with LVTA-SCD events. The levels of glutamate and urea were positively and negatively relevant to AB-SCD events, respectively. The dangerous metabolites indicated that lower levels of energy substrates, severe hypoxia, the inhibition of transamination and hyper sympathetic excitement and reactive oxygen species in myocardia were vulnerable to SCD during acute MI. The results suggest fatal metabolic alterations correlated with SCD events during acute MI, which could offer novel clues for the prevention or treatment of acute MI-related SCD.
Highlights
Sudden cardiac death (SCD) is the leading cause of death worldwide
The levels of isoleucine, lactate, glutamate choline, phosphorylcholine, taurine and asparagine in ischemic myocardia were positively associated with lethal ventricular tachyarrhythmia (LVTA)-SCD events; in contrast, the levels of alanine, urea, phenylalanine, linoleic acid, elaidic acid and stearic acid were inversely correlated with LVTA-SCD events
Using gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H-NMR)-based tissue metabolomics, we aimed to assess the global difference in myocardial metabolism between the rats who occurred SCD and those who survived during acute Myocardial ischemia (MI) and analyse myocardial metabolic alterations correlated with SCD events
Summary
Sudden cardiac death (SCD) is the leading cause of death worldwide. It accounts for approximately 560 000 deaths and 200 000–450 000 deaths annually in China and the USA, respectively [1,2]. Myocardial metabolism would firstly be affected post MI, which may lead to lethal consequences, including SCD [3]. Several metabolic changes, such as lower ATP and increased level of reactive oxygen species (ROS), have been linked to SCD [4,5]. Metabolic bases inducing SCD under condition of acute MI need deeper exploration. Using gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H-NMR)-based tissue metabolomics, we aimed to assess the global difference in myocardial metabolism between the rats who occurred SCD and those who survived during acute MI and analyse myocardial metabolic alterations correlated with SCD events
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