Metabolic modulation of acute myocardial infarction

Acute myocardial infarction (AMI) continues to be the major determinant of death and disability in Western countries. Despite large improvements in management during the past 20 years, its high morbidity and mortality rates provide a stimulus to search intensively for different and widely applicable therapeutic options. Reperfusion strategies (i.e., thrombolytic drugs or primary angioplasty) along with heparin, aspirin, beta-blockers and angiotensin-converting enzyme (ACE)-inhibitors are the first-line treatments for AMI. New insights into the molecular basis of the dynamic thrombotic process underlying the abrupt closure of an epicardial coronary artery have guided research toward refining antithrombotic drugs and regimens (i.e., direct thrombin-inhibitors and potent antiplatelet drugs such as glycoprotein IIb/IIIa receptor antagonists) to achieve and maintain high reperfusion rates.(8) The concept of metabolic manipulation of the ischemic but viable myocardium (myocardium that is not yet necrotic) is based on the fact that ischemia is essentially a metabolic event and that simple measures affecting myocardium metabolism can reverse or ameliorate the consequences of the ischemic insult. Such measures can produce a favorable balance that promotes the structural and functional recovery and integrity of the ischemic myocardium.(6) During an acute ischemic event such as an AMI, myocardial energy depends on lipids (free fatty acids, FFAs). Although FFAs produce more adenosine triphosphate (ATP) than glucose metabolism, they require more oxygen and therefore are less efficient (glucose metabolism produces a 12% greater yield of ATP per mole of oxygen consumed). In an acute ischemic episode, this is of crucial importance. Improving myocardial metabolism and reducing oxygen demand would have a salutary impact on the prognosis of ischemic myocardium. A commonly proposed metabolic intervention - high concentrations of glucose with the addition of insulin and potassium (GIK) - first was reported as beneficial based on the suppression of arrhythmias and the acceleration of the process of ST resolution during an AMI.