Validity Study of Glutamine to Improve Cardiac Function in Cardiac Surgery

• Troponin I(cTnI) [ Time Frame: postanescesia before surgery, 6, 20 hours after CPB ] [ Designated as safety issue: No ]
  CTnI is a sensitive indicator of myocardial damage.
• Brain Natriuretic Peptide (BNP) [ Time Frame: postanescesia before surgery, 6, 20 hours after CPB ] [ Designated as safety issue: No ]
  BNP is a sensitive indicator of cardiac dysfunction.
• Systemic inflammation [ Time Frame: postanescesia before surgery, 2, 20 hours after CPB ] [ Designated as safety issue: No ]
  Blood levels of Interleukin-6（IL-6）、Tumor Necrosis Factor（TNF-a） and Malondialdehyde (MDA) will be measured.
• Blood concentration of Gln [ Time Frame: postanescesia before surgery, 2, 20 hours after CPB ] [ Designated as safety issue: No ]
  We want to be sure that the blood concentration of Gln was increased compared to the control group after intravenous glutamine supplementation.
• Heart issue HSP-70 [ Time Frame: 20 minutes after CPB ] [ Designated as safety issue: No ]
  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.
• Heart issue O-GlcNAc [ Time Frame: 20 minutes after CPB ] [ Designated as safety issue: No ]
  The same mass of heart tissue described above will be used for the measurements.
• Recovery index [ Time Frame: Date of surgery until date of hospital discharge (an expected average of 2 weeks) ] [ Designated as safety issue: Yes ]
  Recovery index include duration of mechanical ventilation、duration of ICU stay、duration of hospital stay、adverse event and mortality.

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 concentration of blood Gln, 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.

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.

• Rheumatic Heart Disease
• Coronary Heart Disease

• 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 Name: Dipeptiven (N(2)-L-Alanine L-Glutamine dipeptide)
• Drug: Amino acid
  Compound amino acid 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation).Injection rate = 6ml/kg/h.
  Other Names:

  • Compound Amino Acid Injection(18AA－Ⅱ)
  • Novamin
• Drug: Ringer's solution
  Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation). Injection rate = 6ml/kg/h.

• 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).
  Intervention: Drug: Glutamine
• Placebo Comparator: Amino acid
  Compound amino acid 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation).
  Intervention: Drug: Amino acid
• Placebo Comparator: Ringer's solution
  Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation).
  Intervention: Drug: Ringer's solution

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