Early Detection of Ischemic Myocardial Damage by Glycogen Phosphorylase Isoenzyme BB: A Biomarker for Evaluation of Chest Pain and Evolving Infarction in Patients

As with any new test, novel cardiac markers must meet basic analytical and clinical performance standards. As far as sensitivity and specificity are concerned, it is important to know the nature of the proteins immediately released into the blood after cardiac damage. Early identification and confirmation of acute myocardial injury is essential for appropriate patient care and management in the emergency department. In this respect, glycogen phosphorylase (GP) is a sensitive, early released, and suitable cardiac marker protein. This enzyme plays an essential role in the anaerobic energy metabolism during myocardial oxygen deficiency. In the aerobic heart muscle, GP and glycogen are closely associated with the vesicles of the sarcoplasmic reticulum. In tissue, hypoxic glycogen degradation is catalyzed by the GP isoenzyme BB, which is the main isoform in the human myocardium. Ischemia favours the temporary conversion of GPBB into the phosphorylated a form thereby accelerating glycogen breakdown. Within minutes the cytosolic GPBB is dephosphorylated to the b form which is then free to circulate in the cytoplasm. GPBB can diffuse out of the cell if cell membrane permeability is also increased, as is usually the case in hypoxia. This sequence reflects a unique structural and functional interaction between GPBB and the ischemic-sensitive process of glycogenolysis and membrane alteration. This concept is novel and differs from that of other markers of myocardial damage, such as myoglobin, creatine kinase(s), and troponins, as well as fatty-acid-binding proteins, when the efflux reflects alterations in cell membrane integrity. The clinical application of GPBB as a marker of ischemic myocardial injury is a very promising tool for increasing our knowledge of the severity of myocardial ischemic events in various coronary syndromes. This is based on the successful development of specific monoclonal antibodies to the native GPBB isozyme isolated from human heart muscle. Recent data have demonstrated a significantly greater discriminating power of GPBB for the detection of acute ischemic coronary syndromes compared with all other tested markers, including myoglobin and troponin T. GPBB is not only the most sensitive marker for the early detection of myocardial infarction but is also an indicator of cardiac damage in patients with unstable angina pectoris showing reversible ECG ST-T changes. The properties of this new marker are most likely explained by its exclusive role in cardiac glycogenolysis, rapidly accelerating the supply of energy to the ischemic heart. A new and modern method involving an immunoenzymometric assay will soon be commercialized by DIAGENICS AG Dusseldorf, Germany.