Validity Study of Glutamine to Improve Cardiac Function in Cardiac Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Rheumatic Heart Disease, Coronary Heart Disease

Intervention / Treatment
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* Drug: Glutamine
* Drug: Ringer's solution


Participation Criteria
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Eligibility Criteria
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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

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glutamine<br>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<br>* 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<br>* Other names: Dipeptiven (N(2)-L-Alanine L-Glutamine dipeptide);|
| Placebo Comparator: Ringer's solution<br>Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation). | Drug: Ringer's solution<br>* Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation). Injection rate = 6ml/kg/h.<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glutamine, Cardiosurgery, Cardiopulmonary bypass, Cardiac function, Recovery