The Principles of Metabolic Therapy for Heart Disease Anthony Hadj, Salvatore Pepe, PhD, Silvana Marasco, FRACS and Franklin Rosenfeldt, MD, FRACS The Cardiac Surgical Research Unit, Department of Cardiothoracic Surgery, Alfred Hospital and Baker Heart Research Institute, Melbourne, Victoria, Australia Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. First, for some systems, a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Second, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapy such as the use of ACE Inhibitors b-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes. In this review we highlight some metabolic substances that have potential benefit in treating heart disease or improving outcomes after cardiovascular interventions. Glucose-insulin-potas- sium therapy is protective against myocardial ischaemia by elevating myocardial glycogen levels. Coenzyme Q 10 is a lipid-soluble antioxidant that plays a crucial role in cellular ATP production. Magnesium orotate, a key intermediate in the biosynthetic pathway of glycogen, has been shown to improve the energy status of the cell and improve recovery from cardioplegic arrest. The amino acid aspartate plays an important role in providing energy substrates for oxidative phosphorylation in the myocyte. By improving cellular energy production, metabolic therapy has the potential to benefit cardiac function during the stress of cardiac surgery, myocardial infarction and cardiac failure. (Heart, Lung and Circulation 2003; 12: S55–S62) Key words: asparate, coenzyme Q 10 , glucose-insulin-potassium, magnesium orotate, metabolic therapy. ecovery of energy metabolism is an important part of the healing and repair process after stress. The most common form of stress in the heart is ischaemia-reperfusion injury which is seen during cardiac surgery, angioplasty and thrombolysis. At a cel- lular level ischaemia-reperfusion injury results in loss of ionic homeostasis, energy depletion, oxygen free radical mediated damage to cellular structures, and sodium and calcium overload. Acute myocardial infarction is a stress that produces changes not only in the infarcted area itself, but also in the noninfarcted myocardium where it causes energy depletion followed by hypertrophy. Other energy- demanding stresses are hypoxia and catecholamine stim- ulation, which occur in the recovery period after cardiac surgery. Targeted metabolic therapy is an under-utilised method of treatment for heart disease. This form of therapy differs fundamentally from standard cardiovas- cular pharmacological therapy with ACE Inhibitors β- blockers, statins and calcium channel antagonists, which block rather than enhance cellular processes. Metabolic therapy involves the administration of a substance nor- mally occurring in the body to favourably influence a metabolic reaction occurring within the cell (Fig. 1). This can occur in two ways: 1 A substance can be given to achieve greater than normal levels in the body so as to drive a enzymic reac- tion in the preferred direction. For example glucose- insulin-potassium can be given to enhance glycolysis and so produce more energy in the cell. Correspondence: Associate Professor Franklin Rosenfeldt, Cardiac Surgical Research Unit, CJOB Cardiothoracic Department, Alfred Hospital, PO Box 315, Prahran 3181, Australia. Email: f.rosenfeldt@alfred.org.au R