MicroRNA Mediates Volatile Anesthetics Preconditioning Induced Artery Protection

Study Overview
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Brief Summary
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It has been reported that volatile anesthetics preconditioning mediates protection of organ via microRNA. We want to study on the effects of isoflurane preconditioning on expression of microRNA and mRNA in the specimens of internal mammary artery and ascending aorta.

Detailed Description
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Sixty patients scheduled for off-pump coronary artery bypass surgery were randomly assigned to isoflurane wash-in/wash-out group(S-I group, n=30)or propofol intravenous anesthesia group(P group, n=30). Anesthesia and monitoring method All patients were monitored according to the American Society of Anesthesia guidelines and received standard general induction of anesthesia. SI group:10min after intubation,begin to isoflurane wash-in/wash-out operation:isoflurane administration was interrupted for at least 10 min,by washout with a high fresh gas flow(10 l/min)to achieve a MAC value below 0.2. Following the interruption,sevoflurane was again washed in with a high fresh gas flow(6 l/min)to achieve 1 MAC end-tidal concentration as soon as possible,and repeated twice periods of 10 minutes.Discontinuation of the halogenated agent for at least 15 minutes during the last wash out time. P Group:propofol infusion 3-5μg/kg/h. When isoflurane inhaled anesthetic,propofol are stopped infusion.If during this interruption the BIS value increased to>50,0.5 mg/kg propofol was administered repeatedly in boluses until the BIS value have returned to<50. 6.1h after isoflurane preconditioning,specimens of internal mammary artery(surplus arterial tissue is obtained from the repair internal mammary artery)and ascending aorta(the stump after ascending aortic punch)will be saved, and before isoflurane preconditioning,1h,3h,5h after isoflurane preconditioning, central venous blood samples will also be drawn.

Official Title
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Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University

Conditions
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Coronary Artery Bypass Graft Triple Vessel

Intervention / Treatment
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* Drug: volatile anesthetics(isoflurane)
* Drug: propofol intravenous anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18 years written informed consent; scheduled procedures; planned isolated OPCABG(multiple bypass are allowed; planned combined intervention such as CABG plus valve surgery are not allowed); ejection fraction> 50%; NYHA class Ⅱ Ⅲ; serum creatinine <150μmol / l; preoperative platelet content > 100 × 109 / l; preoperative hemoglobin> 120 g / l Exclusion Criteria: pregnancy; planned valve surgery or surgery on the aorta; left main coronary artery stenosis> 75%; echocardiographic examination revealed moderate to severe mitral, tricuspid, or aortic regurgitation or stenosis; unstable or ongoing angina; recent (< 1 month) or ongoing acute myocardial infarction; use of sulfonylurea, theophylline or allopurinol; previous unusual response to an anesthetic agent; inclusion in other randomised controlled studies in the previous 30 days; (10)any general anesthesia performed in the previous 30 days; emergency operation (not scheduled); kidney or liver transplant in medical history, liver cirrhosis (Child B or C); chronic respiratory disease (such as chronic obstructive pulmonary emphysema)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: volatile anesthetics group<br>10min after intubation, begin to sevoflurane wash-in / wash-out operation: sevoflurane administration was interrupted for at least 10 min, by washout with a high fresh gas flow (10 l/min) to achieve a MAC value below 0.2. Following the interruption, sevoflurane was again washed in with a high fresh gas flow (6 l/min) to achieve 1 MAC end-tidal concentration as soon as possible, and repeated twice periods of 10 minutes. Discontinuation of the halogenated agent for at 15 minutes during the last wash out time. | Drug: volatile anesthetics(isoflurane)<br>* volatile anesthetics wash-in / wash-out operation<br>|
| Placebo Comparator: propofol intravenous anesthesia group<br>propofol infusion 3-5μg / kg / h | Drug: propofol intravenous anesthesia<br>* propofol infusion 3-5μg / kg / h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| microRNA |  | 1h after isoflurane treatment(specimens of internal mammary artery and ascending aorta stump are saved) | 
| NOS3 mRNA,mRNA levels of adhesion molecule selectin -E,vascular cell adhesion molecule -1,vascular endothelial growth factor -1,intercellular adhesion molecule,RhoA and ROK |  | 1h after isoflurane treatment(specimens of internal mammary artery and ascending aorta stump are saved) | 
| phosphatidylinositol-3-kinase,alanine aminotransferase,endothelial nitric oxide synthase |  | 1h after isoflurane treatment(specimens of internal mammary artery and ascending aorta stump are saved) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from microRNA |  | befor isoflurane treatment,1h,3h,5h after isoflurane treatment(central venous blood samples are drawn) | 
| Change from ON content in serum,vascular cell adhesion molecule-1,intercellular adhesion molecules-1,adhesion molecule selectin-E,monocyte chemoattractant protein-1 and vascular endothelial growth factor-1 |  | befor isoflurane treatment,1h,3h,5h after isoflurane treatment(central venous blood samples are drawn) | 
| Change from tumor necrosis factor-a,interleukin 1β,IL-6,IL-8 and IL-10 |  | befor isoflurane treatment,1h,3h,5h after isoflurane treatment(central venous blood samples are drawn) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Volatile Anesthetics, MicroRNA, Off-pump Coronary Artery Bypass Surgery, Internal Mammary Artery, Ascending Aorta