endothelin-1 and Coronary-Occlusion

Sudden cardiac death constitutes a major health-related problem. In the majority of cases, sudden cardiac death is due to ventricular tachyarrhythmias secondary to acute myocardial infarction. The pathophysiologic chain of events leading to ventricular tachyarrhythmias after acute coronary occlusion is complex and incompletely understood. Experimental and clinical studies have indicated that endothelin-1 production rises markedly very early in the course of myocardial infarction. Endothelin-1 exerts significant electrophysiologic actions on ventricular cardiomyocytes and participates in the genesis of ischemic ventricular tachyarrhythmias. Endothelin-1, acting via two G-protein-coupled receptors (ETA and ETB), prolongs the action potential duration and increases the occurrence of spontaneous calcium transients, resulting in early afterdepolarizations and ventricular tachyarrhythmias via triggered activity. Moreover, endothelin-1 enhances sympathetic stimulation, a well established contributor to ventricular arrhythmogenesis during acute myocardial infarction. Despite these considerations, the therapeutic potential of endothelin receptor antagonists as antiarrhythmic drugs during myocardial ischemia/infarction is still under investigation. To date, a number of endothelin-1 receptor antagonists are available, presenting different degrees of selectivity for ETA and ETB receptors. The arrhythmogenic effects of endothelin-1 are exerted mainly via stimulation of the ETA receptors, but the role of ETB receptors remains controversial, as previous studies have produced conflicting results. This review summarizes the current state-of-the-art on the role of endothelin-1 in the genesis of ventricular arrhythmias during acute myocardial infarction and raises some hypotheses that could be explored in future studies.

Topics: Animals; Coronary Occlusion; Endothelin-1; Humans; Myocardial Infarction; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin; Signal Transduction; Sympathetic Nervous System; Tachycardia, Ventricular

Coronary collateral circulation (CCC) plays an important role in protecting myocardium from ischemic damage. The studies on factors which impact on CCC might be of great clinical interest. The aim of the present study was to evaluate endothelin-1 (ET-1) as a potential predictor for poor or good CCC in patients with angiography-proven ≥95% coronary occlusion.. We screened 1038 consecutive patients with ≥95% occlusion in at least one major epicardial coronary artery detected by coronary angiography. Of these, 663 patients were classified into the poor CCC group with Rentrop 0-2 grade collateral circulation and 375 patients into the good CCC group with Rentrop 3 grade. The association of plasma ET-1 levels with collateral status was assessed.. We found that patients in the poor CCC group had a higher ET-1 level than those in the good CCC group (0.59±0.48 vs. 0.39±0.32pmol/L, p<0.001), and the ET-1 values increased with the descent of the Rentrop grades (p for trend<0.001). Moreover, multivariate logistic regression analysis revealed an independent association between ET-1 and collateral status (odds ratio [95% CI] for poor CCC 2.27 [1.60-3.22], p<0.001). Additionally, the association presented significance in both men (odds ratio [95% CI] for poor CCC 3.18 [2.20-4.74], p<0.001) and women (odds ratio [95% CI] for poor CCC 3.10 [1.36-7.85], p=0.011) when the sex-specific analysis was performed.. Plasma ET-1 level may be a useful, easily available marker for predicting the degree of CCC in patients with ≥95% coronary chronic occlusion.

Topics: Aged; Biomarkers; Collateral Circulation; Coronary Circulation; Coronary Occlusion; Coronary Vessels; Endothelin-1; Female; Humans; Male; Middle Aged

The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation.

Topics: Aldosterone; Animals; Antioxidants; Captopril; Collagen; Coronary Occlusion; Coronary Vessels; Endothelin-1; Glucosides; Heart Ventricles; Hydroxyproline; Hypertrophy; Male; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Nitric Oxide; Phytotherapy; Plant Extracts; Polygonum; Rats, Sprague-Dawley; Renin-Angiotensin System; Stilbenes; Ventricular Remodeling

Predicting the likely success of primary PCI to salvage potential infarcted myocardium is desirable. We compared early invasive parameters of coronary microcirculation function with the levels of circulating endothelin (ET-1) and 6-month ejection fraction after STEMI.. Forty-four STEMI patients underwent assessment of coronary flow reserve (CFR) and index of myocardial resistance (IMR) on completion of PPCI and one day later. Cardiac magnetic resonance (CMR) at 24 h and 6 months assessed ejection fraction, oedema, late gadolinium enhancement, and salvage. In patients with depressed EF, there was no difference in IMR or CFR measured immediately after PPCI compared with those with preserved EF. However, by Day 1, CFR was significantly lower in those with depressed EF [2.0(1.5-2.3) vs. 2.6(2.1-3.3), P = 0.008]. In multivariable models, higher CFR post-PPCI [EST: +8.9 (SE 3.7) per 1 CFR unit, P = 0.03] and greater increase in CFR between post-PPCI and Day 1 [EST: +8.5 (SE 3.4) per 1 CFR unit, P = 0.01] were associated with higher salvage index. Circulating endothelin levels were significantly elevated in the low EF group at both 6 and 24 h, and 24 h levels correlated with CFR.. Changes of the coronary microcirculation in the first day after PPCI are associated with 6-month ejection fraction and myocardial salvage. Depressed CFR at 24 h is associated with CMR imaging indices of MVO and haemorrhage and elevated endothelin levels.

Topics: Coronary Circulation; Coronary Occlusion; Coronary Vessels; Endothelin-1; Female; Hemorrhage; Humans; Magnetic Resonance Angiography; Male; Microcirculation; Microvessels; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Recovery of Function; Stroke Volume; Vascular Resistance