Validity Study of Glutamine to Improve Cardiac Function in Cardiac Surgery

Intravenous Supplementation of Glutamine Preoperatively for Cardiac Function and Recovery Improvement in Adult Accepting Cardiosurgery: A Randomized, Double-Blinded, Placebo-Controlled Trial

In view of the lack of large-scale clinical study and potent evidence-based medicine, the investigators designed a randomized, double-blind, placebo-controlled study to ascertain whether preoperative intravenous administration with glutamine can improve the postoperative cardiac function and prognosis of adult patients undergoing cardiac surgery. The investigators want to detect the levels of myocardial protein O-GlcNAc modification and HSP70 expression, changes in sensitive indicators of myocardial injury, systemic inflammatory reaction and oxidative stress levels, and to examine the correlation between these changes and Clinical manifestations. The ultimate goal of the study is to explore a new way for clinical myocardial protection.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease; Rheumatic Heart Disease
• Intervention / Treatment: Drug: Glutamine; Drug: Ringer's solution

Detailed Description

Cardiosurgery is mostly done under cardiopulmonary bypass. However, the cardiopulmonary bypass and the later recovery of spontaneous circulation, a cardiac ischemia / reperfusion process, may cause myocardial damage and affect cardiac function as well as prognosis.

Glutamine, an amino acid abundant in the human body, plays an important role in the regulation of metabolism and immune cells and the protection of organs. Relative lack of glutamine is reported during stress or serious illness. Animal studies have confirmed that pretreatment with glutamine has a protective effect on the heart, liver, kidney and other organs post ischemia / reperfusion injury. It is also established that glutamine exerts myocardial protection mainly by activating hexosamine biosynthetic pathway, increasing intracellular O-GlcNAc protein modification and expression of heat shock protein 70 (HSP70), starting the protective reaction in the body, improving the function of myocardial cells, and inhibiting the release of inflammatory cytokines and oxidative stress levels. Besides, clinical studies have shown that at the perioperative stage glutamine has a protective effect on cardiac function of the patients treated with pump coronary artery bypass surgery.

The purpose of this study is to ascertain whether preoperative intravenous administration with glutamine (as compared with control group) can improve the postoperative cardiac function and prognosis of adult patients undergoing cardiac surgery and reduce inflammatory response and oxidative stress levels of the body. The correlation between Clinical manifestations and expression of myocardium O-GlcNAc and HSP70 will also be investigated.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with coronary artery disease or rheumatic heart disease accepted cardiosurgery under cardiopulmonary bypass

Exclusion Criteria:

• ejection fraction(EF)<50%
• Preoperative support with intra-aortic balloon pump(IABP)
• Hepatosis
• Renal dysfunction
• Myocardial infarction attack within 3 months
• Emergency operation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glutamine; 20% N(2)-L-alanyl-L-glutamine 0.4g/kg(2ml/kg) mixed with compound amino acid (10ml/kg)(volume ratio=1:5).Intravenous injection twice (24 hours、1 hour before operation).	Drug: Glutamine; 20% N(2)-L-alanyl-L-glutamine 0.4g/kg(2ml/kg) mixed with compound amino acid (10ml/kg).Intravenous injection twice (24 hours、1 hour before operation). Injection rate = 6ml/kg/h; Other Names: Dipeptiven (N(2)-L-Alanine L-Glutamine dipeptide)
Placebo Comparator: Ringer's solution; Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation).	Drug: Ringer's solution; Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation). Injection rate = 6ml/kg/h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
perioperative changes of Cardiac Index (CI)	For each patient,a Swan-Ganz catheter will be inserted after anesthesia induction.CI and other values of hemodynamics will be measured.	postanescesia before surgery, 2, 20 hours after cardiopulmonary bypass (CPB)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Troponin I(cTnI)	CTnI is a sensitive indicator of myocardial damage.	postanescesia before surgery, 6, 20 hours after CPB
Brain Natriuretic Peptide (BNP)	BNP is a sensitive indicator of cardiac dysfunction.	postanescesia before surgery, 6, 20 hours after CPB
Systemic inflammation	Blood levels of Interleukin-6（IL-6）、Tumor Necrosis Factor（TNF-a） and Malondialdehyde (MDA) will be measured.	postanescesia before surgery, 2, 20 hours after CPB
Heart issue HSP-70	A mass of heart tissue (a part of right auricle of heart,weigh about 50mg) will be cut 20 minutes after CPB for the measurements.	20 minutes after CPB
Heart issue O-GlcNAc	The same mass of heart tissue described above will be used for the measurements.	20 minutes after CPB
Recovery index	Recovery index include duration of mechanical ventilation、duration of ICU stay、duration of hospital stay、adverse event and mortality.	Date of surgery until date of hospital discharge (an expected average of 2 weeks)

Collaborators and Investigators

• Sponsor: Yuejiang Liu

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: February 4, 2013
• First Submitted That Met QC Criteria: February 16, 2013
• First Posted (Estimate): February 20, 2013

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 27, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Recovery; Cardiac function; Glutamine; Cardiopulmonary bypass; Cardiosurgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Arteriosclerosis; Arterial Occlusive Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Rheumatic Fever; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Rheumatic Heart Disease
• Other Study ID Numbers: glncardio001