Coronary Artery Bypass and Nitrate Oral Supplementation

Study Overview
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Brief Summary
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The purpose of this study is to determine whether oral sodium nitrate administration prior to coronary artery bypass surgery can reduce perioperative levels of troponin T. In addition, plasma and urine surrogate markers of renal, hepatic and brain injury will be monitored.

Detailed Description
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Nitric oxide (NO) is an important mediator in the cardiovascular system and has been shown to have protective properties in ischemia-reperfusion injury. Inorganic nitrate, an oxidation product from endogenous NO production and also a constituent in green leafy vegetables, can be recycled, via nitrite, back to bioactive NO in the body. Recent research has shown beneficial effects of nitrate and nitrite in animal models of myocardial ischemia-reperfusion injury. Moreover, dietary nitrate reduces blood pressure and oxygen cost during exercise in humans. During coronary bypass surgery the heart undergoes ischemia-reperfusion injury and troponin T is most often released from the myocardium. The aim of the present study is to investigate if preoperative inorganic nitrate, in doses easily achievable from the diet, can affect troponin T release as well as other surrogate markers of injury to the liver, kidneys and the brain. In addition, plasma and urine samples will be collected for markers of oxidative stress and inflammation (sCRP and cytokines). Patients planned for bypass surgery who give their written informed consent will, the night before surgery, get a standardized, low-nitrate meal where after they receive sodium nitrate on two occasions preoperatively; the night before and in the morning before surgery. Plasma and urine samples will be collected at various time points up to 72 hours after surgery.

Official Title
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Effects of Oral Nitrate During Coronary Artery Bypass Surgery

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Dietary Supplement: Sodium nitrate
* Other: Sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing coronary artery bypass surgery Over 18 years of age Exclusion Criteria: Over 80 years of age Pregnancy Reoperation Intended heart valve or additional surgery Angina or troponin release above 45 nmol/L < 48 hours before surgery Medication with organic nitrates/nitrites < 24 hours before surgery Medication with glibenclamide or corticosteroids Significant renal, pulmonary or hepatic disease

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium nitrate<br>Preoperative oral administration of sodium nitrate. 700 mg the night before surgery and 700 mg three hours before surgery | Dietary Supplement: Sodium nitrate<br>* Preoperative oral administration of sodium nitrate. 700 mg the night before surgery and 700 mg three hours before surgery<br>|
| Placebo Comparator: Placebo<br>Preoperative oral administration of sodium chloride the night before surgery and three hours before surgery | Other: Sodium chloride<br>* Preoperative oral administration of sodium chloride the night before surgery and three hours before surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin T release over the perioperative 72-hour period. |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin T release over the perioperative 24-hour period. |  | 24 h | 
| Creatinine kinase myocardial fraction (CKMB) release over the perioperative 72-hour period |  | 72 hours | 
| Creatinine kinase myocardial fraction (CKMB) release over the perioperative 24-hour period |  | 24 hours | 
| Pro Brain natriuretic peptide (proBNP) release over the perioperative 72-hour period. |  | 72 hours | 
| Aspartate aminotransferase (AST) release over the perioperative 72-hour period. |  | 72 hours | 
| Alaninaminotransferas (ALAT) release over the perioperative 72-hour period. |  | 72 hours | 
| Alkaline phosphatase (ALP) release over the perioperative 72-hour period. |  | 72 hours | 
| Bilirubin release over the perioperative 72-hour period |  | 72 hours | 
| Creatinine release over the perioperative 72-hour period |  | 72 h | 
| Cystatin C release over the perioperative 72-hour period |  | 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sodium nitrate, coronary artery bypass surgery, ischemia-reperfusion, myocardial injury