MicroRNA Mediates Volatile Anesthetics Preconditioning Induced Artery Protection

Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Bypass Graft Triple Vessel
• Intervention / Treatment: Drug: volatile anesthetics(isoflurane); Drug: propofol intravenous anesthesia

Detailed Description

1. 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).
2. Anesthesia and monitoring method All patients were monitored according to the American Society of Anesthesia guidelines and received standard general induction of anesthesia.
3. 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.
4. P Group:propofol infusion 3-5μg/kg/h.
5. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100038
      • Recruiting
      • Beijing Anzhen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: volatile anesthetics group; 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); volatile anesthetics wash-in / wash-out operation
Placebo Comparator: propofol intravenous anesthesia group; propofol infusion 3-5μg / kg / h	Drug: propofol intravenous anesthesia; propofol infusion 3-5μg / kg / h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Liang Zhang

Publications and helpful links

General Publications

• Zhang L, Wang CB, Li B, Lin DM, Ma J. RhoA/rho-kinase, nitric oxide and inflammatory response in LIMA during OPCABG with isoflurane preconditioning. J Cardiothorac Surg. 2019 Jan 25;14(1):22. doi: 10.1186/s13019-019-0835-9.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: January 23, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Estimate): February 10, 2016
• Last Update Submitted That Met QC Criteria: February 5, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: MicroRNA; Ascending Aorta; Volatile Anesthetics; Off-pump Coronary Artery Bypass Surgery; Internal Mammary Artery
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Hypnotics and Sedatives; Anesthetics, Inhalation; Anesthetics; Propofol; Isoflurane
• Other Study ID Numbers: 2015017X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED