Abstract
Background: Ventricular tachyarrhythmias are the most common and often the first manifestation of coronary heart disease and lead to sudden cardiac death (SCD). Early detection/identification of acute myocardial ischaemic injury at risk for malignant ventricular arrhythmias in patients remains an unmet medical need. In the present study, we examined the sphingolipids level after transient cardiac ischaemia following temporary coronary artery occlusion during percutaneous coronary intervention (PCI) in patients and determined the role of sphingolipids level as a novel marker for early detection of human myocardial ischaemic injury.Methods and Results: Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) from 31 patients aged 40–73 years-old at 1, 5 min, and 12 h, following elective PCI. Plasma sphingolipids levels were assessed by HPLC. At 1 min coronary sinus levels of sphingosine 1-phosphate (S1P), sphingosine (SPH), and sphinganine (SA) were increased by 314, 115, and 614%, respectively (n = 7), while peripheral blood levels increased by 79, 68, and 272% (n = 24). By 5 min, coronary sinus S1P and SPH levels increased further (720%, 117%), as did peripheral levels of S1P alone (792%). Where troponin T was detectable at 12 h (10 of 31), a strong correlation was found with peak S1P (R2 = 0.818; P < 0.0001).Conclusion: For the first time, we demonstrate the behavior of plasma sphingolipids following transient cardiac ischaemia in humans. The observation supports the important role of sphingolipids level as a potential novel marker of transient or prolonged myocardial ischaemia.
Highlights
Despite recent advances in preventing sudden cardiac death (SCD) due to cardiac arrhythmia, its incidence in the population at large has remained unacceptably high
For the first time, we demonstrate the behavior of plasma sphingolipids following transient cardiac ischaemia in humans
The observation supports the important role of sphingolipids level as a potential novel marker of transient or prolonged myocardial ischaemia
Summary
Despite recent advances in preventing sudden cardiac death (SCD) due to cardiac arrhythmia, its incidence in the population at large has remained unacceptably high. About 80% of SCDs are caused by ventricular tachyarrhythmias that often occur without warning, leading to death within minutes in patients who do not receive prompt medical attention It is the most common and often the first manifestation of coronary heart disease. Acute myocardial ischaemia is associated with dramatic electrophysiological alterations that may lead to malignant ventricular arrhythmias which occur within minutes of cessation of coronary flow and are rapidly reversible with reperfusion This suggests that subtle and reversible biochemical and/or ionic alterations within or near the sarcolemma of myocardium during the early stage of acute ischaemic injury may contribute to the electrophysiological instability. Detection/identification of acute myocardial ischaemic injury at risk for malignant ventricular arrhythmias in patients remains an unmet medical need. We examined the sphingolipids level after transient cardiac ischaemia following temporary coronary artery occlusion during percutaneous coronary intervention (PCI) in patients and determined the role of sphingolipids level as a novel marker for early detection of human myocardial ischaemic injury
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