endothelin-1 and No-Reflow-Phenomenon

To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits.. Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated.. SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05).. Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Dexmedetomidine; Disease Models, Animal; Endothelin-1; Heart Rate; Hemodynamics; Male; Myocardial Reperfusion Injury; No-Reflow Phenomenon; Platelet Activating Factor; Rabbits; Random Allocation; Reference Values; Reproducibility of Results; Thromboxane A2; Treatment Outcome

BACKGROUND No-reflow phenomenon is a well-known problem, often accompanying percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEAMI). This study investigated the value of plasma D-dimer and Endothelin-1 (ET-1) levels on admission in predicting no-reflow after primary PCI and long-term prognosis in STEAMI patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS There were 822 patients with STEAMI and T2DM undergoing successful primary PCI included in this study: 418 patients showed normal re-flow after PCI, while 404 patients showed no-reflow phenomenon after PCI. The predictive value of plasma ET-1 and D-dimer level, and other clinical parameters for the no-reflow phenomenon were analyzed. RESULTS The high plasma ET-1 and D-dimer levels showed predictive value for the no-reflow phenomenon in STEAMI patients with T2DM. Patients with high D-dimer and ET-1 levels showed higher risk (4.212, with 95%CI of 2.973-5.967 and 2.447 with 95%CI of 1.723-3.476, respectively) of no-reflow phenomenon compared with patients with low plasma D-dimer and ET-1 levels. Sensitivity of high plasma ET-1 and D-dimer levels in predicting no-reflow was 0.766. Both plasma D-dimer and ET-1 were adverse prognosticators for STEAMI patients with a T2DM post PCI (P<0.001). CONCLUSIONS In conclusion, plasma D-dimer and ET-1 levels on admission independently predict no-reflow after PCI in STEAMI patients with T2DM. When combined, the D-dimer and ET-1 levels as predictive and prognostic values are clinically promising. The plasma D-dimer and ET-1 levels provided a novel marker for treatment selection for the STEAIM patients with a T2DM history.

Topics: Diabetes Mellitus, Type 2; Endothelin-1; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Multivariate Analysis; No-Reflow Phenomenon; Percutaneous Coronary Intervention; Prognosis; ROC Curve; Sensitivity and Specificity; ST Elevation Myocardial Infarction

To determine the effect of adiponectin (APN) on the coronary no-reflow (NR) injury in rats with Type 2 diabetes mellitus (T2DM), 80 male Sprague-Dawley rats were fed with a high-sugar-high-fat diet to build a T2DM model. Rats received vehicle or APN in the last week and then were subjected to myocardial ischemia reperfusion (MI/R) injury. Endothelium-dependent vasorelaxation of the thoracic aorta was significantly decreased and serum levels of endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were noticably increased in T2DM rats compared with rats without T2DM. Serum APN was positively correlated with the endothelium-dependent vasorelaxation, but negatively correlated with the serum level of ET-1. Treatment with APN improved T2DM-induced endothelium-dependent vasorelaxation, recovered cardiac function, and decreased both NR size and the levels of ET-1, ICAM-1 and VCAM-1. Hypoadiponectinemia was associated with the aggravation of coronary NR in T2DM rats. APN could alleviate coronary NR injury in T2DM rats by protecting the endothelium and improving microcirculation.

Topics: Adiponectin; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Endothelin-1; Endothelium, Vascular; Intercellular Adhesion Molecule-1; Male; No-Reflow Phenomenon; Rats; Rats, Sprague-Dawley; Vascular Cell Adhesion Molecule-1

Coronary slow flow (CSF) is a special coronary microvascular disorder. The pathogenesis and effective therapeutics of CSF remain unclear. This study aimed to evaluate the global and regional functions of the left ventricle (LV) and investigate the efficacy of nicorandil in patients with CSF.. Thirty-six patients with CSF in the left anterior descending (LAD) branch and 20 patients with normal coronary arteries were included. Global and regional functions of the LV supplied by LAD were measured using conventional Doppler echocardiography and two-dimensional speckle tracking echocardiography, respectively, within 24 h after coronary angiography. Concentrations of plasma nitric oxide (NO) and endothelin-1 (ET-1) were detected using colorimetry and radioimmunoassay, respectively. The function of the LV and the levels of NO and ET-1 were also investigated before and 90 days after treatment with 15 mg/day of nicorandil.. Compared with the control group, the early diastolic peak velocity (E), E/A ratio, and plasma NO levels were lower, whereas the late diastolic peak flow velocity (A) and plasma ET-1 levels were significantly higher in the CSF group (P<0.05). The longitudinal strain rate peak of the LV was reduced significantly in CSF patients (P<0.001). After treatment, 75% (27/36) of CSF patients were free of chest pain. The values of E peak, E/A ratio, longitudinal strain rate peak, and plasma NO level were increased (P<0.001), whereas the ET-1 level was decreased in CSF patients (P<0.001).. Nicorandil may improve chest pain symptoms and the impaired function of the LV, possibly by increasing plasma NO and reducing ET-1 in CSF.

Topics: Aged; Anti-Arrhythmia Agents; Colorimetry; Coronary Angiography; Echocardiography, Doppler; Endothelin-1; Female; Heart; Humans; Male; Middle Aged; Nicorandil; Nitric Oxide; No-Reflow Phenomenon; Radioimmunoassay

No-reflow after primary percutaneous coronary intervention (pPCI) may be reversible. 40 patients undergoing pPCI were evaluated by assessing either improvement or lack of changes regarding angiographic and electrocardiographic indexes of no-reflow between admission and pre-discharge. Myeloperoxidase (MPO; in nanograms per milliliter), C-reactive protein (CRP; in milligrams per liter), endothelin-1 (ET-1; in nanograms per milliliter), angiopoietin-2 (Ang-2, in picograms per milliliter), and their pre-discharge/basal values variations (Δ) were related to no-reflow evolution. ΔMPO and ΔCRP were greater in patients with sustained no-reflow or lack of ST-segment resolution (STR) as compared with those with reversible no-reflow or lack of STR (p = 0.033, p = 0.04, p < 0.001, and p = 0.001, respectively), whereas ΔET-1 was similar in the two groups. ΔAng-2 was greater in patients with sustained no-reflow or lack of STR as compared with those with reversible no-reflow or lack of STR (p = 0.01 and 0.044, respectively). Bigger ΔMPO, ΔCRP (increasing levels), and ΔAng-2 (decreasing levels) are associated with sustained no-reflow, thus they might have a role in no-reflow evolution.

Topics: Aged; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Circulation; Electrocardiography; Endothelin-1; Female; Humans; Inflammation Mediators; Male; Microcirculation; Middle Aged; No-Reflow Phenomenon; Patient Discharge; Percutaneous Coronary Intervention; Peroxidase; Predictive Value of Tests; Prognosis; Time Factors; Vesicular Transport Proteins

Ischemia/reperfusion injury may have deleterious short- and long-term consequences for cardiac allografts. The underlying mechanisms involve microvascular dysfunction that may culminate in primary graft failure or untreatable chronic rejection.. Here, we report that rat cardiac allograft ischemia/reperfusion injury resulted in profound microvascular dysfunction that was prevented by donor treatment with peroral single-dose simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase and Rho GTPase inhibitor, 2 hours before graft procurement. During allograft preservation, donor simvastatin treatment inhibited microvascular endothelial cell and pericyte RhoA/Rho-associated protein kinase activation and endothelial cell-endothelial cell gap formation; decreased intragraft mRNA levels of hypoxia-inducible factor-1α, inducible nitric oxide synthase, and endothelin-1; and increased heme oxygenase-1. Donor, but not recipient, simvastatin treatment prevented ischemia/reperfusion injury-induced vascular leakage, leukocyte infiltration, the no-reflow phenomenon, and myocardial injury. The beneficial effects of simvastatin on vascular stability and the no-reflow phenomenon were abolished by concomitant nitric oxide synthase inhibition with N-nitro-l-arginine methyl ester and RhoA activation by geranylgeranyl pyrophosphate supplementation, respectively. In the chronic rejection model, donor simvastatin treatment inhibited cardiac allograft inflammation, transforming growth factor-β1 signaling, and myocardial fibrosis. In vitro, simvastatin inhibited transforming growth factor-β1-induced microvascular endothelial-to-mesenchymal transition.. Our results demonstrate that donor simvastatin treatment prevents microvascular endothelial cell and pericyte dysfunction, ischemia/reperfusion injury, and chronic rejection and suggest a novel, clinically feasible strategy to protect cardiac allografts.

Topics: Animals; Endothelial Cells; Endothelin-1; Enzyme Inhibitors; Gap Junctions; Graft Rejection; Heart Transplantation; Heme Oxygenase-1; Hypoxia-Inducible Factor 1, alpha Subunit; Major Histocompatibility Complex; Male; Microvessels; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; No-Reflow Phenomenon; Polyisoprenyl Phosphates; Primary Graft Dysfunction; Rats; Rats, Inbred WF; Reperfusion Injury; rho-Associated Kinases; Simvastatin

No-reflow after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) is associated with poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor that might aggravate reperfusion injury. The aim of our study was to assess the relationship between systemic ET-1 levels and the occurrence of no-reflow as well as to evaluate the prognostic value of ET-1 in a high-risk STEMI population.. We examined 128 consecutive patients undergoing primary PCI in acute STEMI <12 hours after symptom onset. Endothelin-1 was assessed before and immediately after primary PCI. Patients were categorized into 2 groups defined by the median ET-1 level on admission. No-reflow was assessed by 3 different methods after PCI: angiographic Thrombolysis in Myocardial Infarction (TIMI) flow and myocardial blush grade, electrocardiographic ST-resolution, and microvascular obstruction (MO) measured by cardiac magnetic resonance imaging (MRI). The primary clinical end points were mortality and major adverse cardiovascular events. Clinical follow-up was conducted after a median of 19 months.. Patients with angiographically (TIMI flow < or =2 or TIMI flow 3 with final myocardial bush grade < or =2 after PCI), electrocardiographically (ST-resolution <30%), and MRI- (presence of MO) detected no-reflow had significantly higher ET-1 levels on admission. At multivariable logistic regression analysis, ET-1 levels on admission were the only significant predictor of MRI-detected no-reflow (P = .03) together with left ventricular ejection fraction (P = .002). An elevated ET-1 level > or = the median on admission was a significant predictor of long-term mortality.. Endothelin-1 on admission is associated with no-reflow and increased long-term mortality in a high-risk STEMI population reperfused by primary PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Endothelin-1; Female; Humans; Image Enhancement; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Infarction; No-Reflow Phenomenon; Prognosis; Prospective Studies; ROC Curve

Thromboxane A2 (TXA2) is a key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction. We sought to investigate whether baseline plasma levels of TXA2 are associated with coronary no-reflow after primary percutaneous coronary intervention (PPCI).. A total of 47 consecutive patients (age, 62.5 +/- 12.7; male sex, 76.6%) admitted to our hospital for a first ST-segment elevation myocardial infarction and undergoing PPCI within 12 h of onset of symptoms were enrolled. Admission TXA2 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Angiographic no-reflow was defined as a final TIMI flow of

Topics: Angioplasty, Balloon, Coronary; Biomarkers; Coronary Angiography; Coronary Circulation; Electrocardiography; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Myocardial Infarction; No-Reflow Phenomenon; Risk Assessment; Thromboxane A2; Treatment Outcome

It has been verified that nicorandil can attenuate myocardial no-reflow. However; the effects of nicorandil on endothelial junctions and Endothelin-1 (ET-1) are unknown.. 40 mini-swines randomized into 5 study groups: 8 in control, 8 nicorandil pretreatment, 8 in glibenclamide (KATP channel blocker)-treated, 8 in nicorandil and glibenclamide-pretreated and 8 in sham-operated. Acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by one-hour reperfusion.. In control group, plasma ET-1 significantly increased, ET-1 or VE-cadherin level in the reflow and no-reflow myocardium was significantly higher or lower than that in normal myocardium. Compared with the control group, nicorandil significantly decreased plasma ET-1 and myocardial tissue ET-1, maintained VE-cadherin level. However, glibenclamide abrogated the protective effect of nicorandil.. The beneficial effect of nicorandil on endothelial junctions could be due to its effect on ET-1 via the activation of KATp channel.

Topics: Animals; Antigens, CD; Cadherins; Coronary Vessels; Disease Models, Animal; Endothelial Cells; Endothelin-1; Glyburide; Injections, Intravenous; Intercellular Junctions; KATP Channels; Ligation; Myocardial Infarction; Myocardium; Nicorandil; No-Reflow Phenomenon; Potassium Channel Blockers; Research Design; Swine; Swine, Miniature; Vasodilator Agents