Nutrition before, during, and after surgery increases the arginine:asymmetric dimethylarginine ratio and relates to improved myocardial glucose metabolism: a randomized controlled trial.
BACKGROUND
Nitric oxide (NO) is essential for the optimal perfusion of the heart and its vasculature. NO may be insufficient in surgical patients because its precursor arginine is decreased, and the inhibitor of NO synthesis asymmetric dimethylarginine (ADMA) is increased. Besides arginine, the presence of other amino acids essential for the proper metabolism of cardiac cells may be decreased too. Supplementation of these amino acids with enteral and parenteral nutrition before, during, and after surgery may augment the myocardial and plasma arginine:ADMA ratio and availability of amino acids. Myocardial glucose metabolism and nutritional conditioning may result in a reduction of cardiac injury and support rapid recovery after major surgery.


OBJECTIVE
We investigated the effect of nutrition before, during, and after surgery on amino acids and the myocardial arginine:ADMA ratio and its relation to myocardial glucose metabolism.


METHODS
In this trial, 33 patients who were undergoing off-pump coronary artery bypass grafting (CABG) were randomly assigned between enteral, parenteral, or no nutrition (control) from 2 d before, during, and until 2 d after surgery. Both enteral and parenteral solutions were prepared with commercially available products and included proteins or amino acids, glucose, vitamins, and minerals. Concentrations of amino acids including ADMA were analyzed in myocardial tissue and plasma samples. ¹⁸F-fluorodeoxyglucose positron emission tomography was performed before and after surgery to assess myocardial glucose metabolism.


RESULTS
The myocardial arginine:ADMA ratio increased during surgery and was significantly higher in the enteral and parenteral groups than in the control group [median (IQR): 115.0 (98.0-142.2) (P = 0.012), 116.9 (100.3-135.3) (P = 0.004), and 93.3 (82.7-101.1), respectively]. Furthermore, the change in the preoperative to postoperative plasma arginine:ADMA ratio correlated with the change in myocardial glucose metabolism in positron emission tomography (r = 0.427, P = 0.033).


CONCLUSIONS
Enteral or parenteral nutrition before, during, and after CABG may positively influence myocardial glucose metabolism by increasing the plasma and myocardial arginine:ADMA ratio.
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Marlieke
M
Visser
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Mariska
M
Davids
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Hein J
HJ
Verberne
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Wouter E M
WE
Kok
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Robert
R
Tepaske
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Riccardo
R
Cocchieri
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Elles M
EM
Kemper
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Tom
T
Teerlink
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Marianne A
MA
Jonker
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Willem
W
Wisselink
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Bas A J M
BA
de Mol
From the Departments of Surgery (MV, WW, and PAMvL), Clinical Chemistry (MD and TT), and Epidemiology and Biostatistics (MAJ), VU University Medical Center, Amsterdam, Netherlands, and the Departments of Cardio-thoracic Surgery (MV, RC, and BAJMdM), Nuclear Medicine (HJV), Cardiology (WEMK), and Pharmacy (EMK) and the Intensive Care Unit (RT), Academic Medical Center University of Amsterdam, Amsterdam, Netherlands.
Paul A M
PA
van Leeuwen
D000368:Aged; D000465:Algorithms; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D047549:Coronary Artery Bypass, Off-Pump / Q000009:adverse effects*; D004750:Enteral Nutrition / Q000009:adverse effects; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009426:Netherlands / Q000453:epidemiology; D009752:Nutritional Status; D010288:Parenteral Nutrition / Q000009:adverse effects; D019990:Perioperative Care; D049268:Positron-Emission Tomography; D011182:Postoperative Care; D011183:Postoperative Complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000517:prevention & control; D011300:Preoperative Care; D012306:Risk
D019788:Fluorodeoxyglucose F18; C018524:N,N-dimethylarginine; D001120:Arginine; D005947:Glucose