Effect of Nicorandil on Cardiac Sympathetic Nerve for the Patients of Acute ST Segment Elevation Myocardial Infarction

Study Overview
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Brief Summary
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The investigators evaluate the effects of intracoronary and intravenous administration of nicorandil on cardiac sympathetic nerve activity and distribution in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Detailed Description
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Reperfusion injury might occur in patients with acute ST segment elevation myocardial infarction undergoing the primary percutaneous coronary intervention(P-PCI),characterized by myocardial stunning, reperfusion-induced arrhythmia, microvascular dysfunction and injury of cardiac sympathetic nerve, etc. Nicorandil is an antianginal agent with a dual mechanism of action: nitrate and K+ATP channel opener. The nitrate action causes vasodilation of systemic veins and epicardial coronary arteries, while the adenosine triphosphate (ATP)-sensitive potassium channel opener action causes vasodilation of peripheral and coronary resistance arterioles. Nicorandil not only decreases preload and afterload but also increases coronary blood flow. The study will compare the effectiveness between nicorandil and placebo of preventing the reperfusion injury especially injury of cardiac sympathetic nerve in patients with acute ST segment elevation myocardial infarction undergoing the P-PCI.It is intended that before reperfusion injury ,nicorandil which was early used by intracoronary injection could prevent and release the microcirculatory spasm, release the coronary microvascular endothelial swelling,decrease embolism of atherosclerotic debris and thrombus formation,moreover,it could reduces the release of norepinephrine from sympathetic endings of the heart directly.So,it could decrease the phenomenon of no-reflow/slow reflow,reperfusion-induced arrhythmia and injury of cardiac sympathetic nerve.

Official Title
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Effects of Nicorandil on Cardiac Sympathetic Nerve Activity and Distribution in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: nicorandil
* Drug: Placebo（normal saline）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute ST-segment elevation myocardial infarction within 12 hours of symptom onset; Age20-80,All genders anterior myocardial infarction The first myocardial infarction The infarct-related artery(IRA) is totally occlusive Blood pressure is higher than 90/60 millimeters of mercury（mmHg） The time from myocardial infarction onset to reach the hospital is less than 12 hs Exclusion Criteria: kidney dysfunction (creatinine >2 mg/dl), History of previous liver disease, Cardiogenic shock, History of myocardial infarction (MI) History of coronary artery bypass grafting History of allergic response to drugs Severe hypovolemia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicorandil<br>Patients who received intracoronary and intravenous nicorandil before and after reperfusion with primary percutaneous coronary intervention | Drug: nicorandil<br>* All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the radial artery using the Seldinger method.The guidewire was passed into the culprit lesion.If the blood flow of culprit vessel reaches TIMI2-3 after balloon dilatation,6mg nicorandil was then administrated before stent implantation, A minimum 5-min interval occurred between the first and second doses of nicorandil to reduce adverse effects, subsequently , 6mg/h ivgtt. up to 48h after coronary intervention<br>* Other names: Experiment Group;|
| Placebo Comparator: Placebo （normal saline）<br>Patients who received intracoronary and intravenous placebo before and after reperfusion with primary percutaneous coronary intervention | Drug: Placebo（normal saline）<br>* All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the radial artery using the Seldinger method.The guidewire was passed into the culprit lesion.If the blood flow of culprit vessel reaches TIMI2-3 after balloon dilatation,6mg placebo was then administrated before stent implantation, A minimum 5-min interval occurred between the first and second doses of placebo to reduce adverse effects, subsequently , 6mg/h ivgtt. up to 48h after coronary intervention<br>* Other names: Control Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the delayed heart/mediastinum count (H/M) ratio | The delayed heart/mediastinum count (H/M) ratio was determined from 123I-meta-iodobenzylguanidine (MIBG) images | 10 days after primary PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The total defect score (TDS) | The total defect score was determined from 123I-meta-iodobenzylguanidine (MIBG) images | 10 days after primary PCI | 
| Rate of slow re-flow/no-reflow phenomenon | TIMI myocardial perfusion grade (TMPG) of the final coronary flow in the culprit artery | 5 minutes after primary PCI | 
| Rate fo complete ST-segment resolution | ST-segment resolution >50 percent in ECG | 2 hours after primary PCI | 
| Rate of unplanned hospitalization for heart failure | Rate of unplanned hospitalization for heart failure | 6 months after primary PCI | 
| The washout rate (WR) | The washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images | 10 days after primary PCI | 
| The total defect score (TDS) | The total defect score was determined from 99mTc-pyrophosphate scintigraphy | 7 days after primary PCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicorandil, primary percutaneous coronary intervention, acute ST segment elevation myocardial infarction, cardiac sympathetic nerve