Search

With a new immunoenzymometric assay we measured human glycogen phosphorylase isoenzyme BB (GPBB) in 116 healthy individuals, 14 patients with stable angina, 107 nontraumatic chest pain patients on admission to the emergency department [45 acute myocardial infarction (AMI), 49 unstable angina, 13 other diseases], and in serial samples from 41 AMI patients. GPBB was compared with creatine kinase (CK), CKMB mass, myoglobin, and cardiac troponin T. Receiver-operating characteristic plots demonstrated the significantly greater (P < or = 0.012) discriminatory power of GPBB to detect acute ischemic coronary syndromes compared with all other tested markers. GPBB was the most sensitive marker for detection of AMI during the first 4 h after onset of chest pain, and only GPBB was increased above the upper reference limit (7 micrograms/L) on admission in patients who had unstable angina at rest and reversible ST-T alterations. This and the high early sensitivity of GPBB are most likely explained by its function as a key enzyme of glycogenolysis.

The diagnosis of myocardial damage is preferably based on measurement of the cardiac-specific troponins. However, there is an emerging need for early, specific cardiac markers. One potential candidate is the glycogen phosphorylase BB isoenzyme (GPBB). We investigated the use of a new, commercially available GPBB ELISA assay in 61 patients presenting with an acute coronary syndrome (37 acute myocardial infarction, 24 unstable angina pectoris) in comparison to established cardiac markers such as troponin T, creatine kinase isoenzyme MB (CKMB) mass, and myoglobin. Blood samples were obtained on arrival, as well as 1, 2, 3, 4, 8, 12 and 24h later. GPBB plasma concentrations were elevated in 90.9% of patients 1h after onset of chest pain and increased to 100% at 4–5h. Within the first 6h, GPBB showed the highest sensitivity (95.5–100%) and high specificity (94–96%) compared to myoglobin (85–95% sensitivity) and CKMB mass (71.4–91.3% sensitivity). As expected, troponin T showed high specificity (100%) and sensitivity >95% later in the time course (≥3h). In un-stable angina pectoris patients, a very high rate of elevated GPBB was observed (93.9% at 3h) compared to myoglobin (66.7%). Cardiac troponin T and CKMB were only elevated in 33.8% and 55.0% of these patients, respectively. In conclusion, GPBB is a promising marker for the early diagnosis of acute coronary syndromes and could probably act as a marker of ischemia. However, further studies on specificity and development of a fast, automated assay are necessary before GPBB can be recommended as a routine diagnostic tool.

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.

OBJECTIVE--To determine whether transient ST-T alterations in patients with unstable angina are associated with an increase in plasma glycogen phosphorylase BB concentrations on admission to hospital. DESIGN--Prospective screening of patients with unstable angina for markers of myocardial cell damage. SETTING--Accident and emergency department of university hospital. PATIENTS--48 consecutive patients admitted for angina pectoris (18 with transient ST-T alterations). None of the patients had acute myocardial infarction according to standard criteria. MAIN OUTCOME MEASURES--Creatine kinase and creatine kinase MB activities, creatine kinase MB mass concentration, and myoglobin, cardiac troponin T, and glycogen phosphorylase BB concentrations on admission. RESULTS--All variables except for creatine kinase and creatine kinase MB activities were significantly higher on admission in patients with unstable angina and transient ST-T alterations than in patients without. However, glycogen phosphorylase BB concentration was the only marker that was significantly (p = 0.0001) increased above its discriminator value in most patients (16). In the 18 patients with transient ST-T alterations creatine kinase MB mass concentration and troponin T and myoglobin concentrations were significantly (p = 0.0001) less commonly increased on admission (in five, three, and two patients, respectively). CONCLUSIONS--The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.

This review deals with glycogen phosphorylase (GP) and its isoenzyme BB in the diagnosis of ischaemic myocardial injury. Early identification and confirmation of acute myocardial infarction is essential for correct patient care and disposition decision in the emergency department. In this respect, glycogen phosphorylase isoenzyme BB (GPBB) based on its metabolic function is an enzyme for early laboratory detection of ischaemia. In the aerobic heart muscle GPBB together with glycogen is tightly associated with the vesicles of the sarcoplasmic reticulum. Release of GPBB, the main isoform in the human myocardium, essentially depends on the degradation of glycogen, which is catalyzed by GP. Ischaemia is known to favour the conversion of bound GP in the b form into GP a, thereby accelerating glycogen breakdown, which is the ultimate prerequisite for getting GP into a soluble form being able to move freely in the cytosol. The efflux of GPBB into the extracellular fluid follows if ischaemia-induced structural alterations in the cell membrane become manifest. The clinical application of GPBB as a marker of ischaemic myocardial injury is a very promising tool for extending our knowledge of the severity of myocardial ischaemic events in the various coronary syndromes. The rational roots of this development were originated from Albert Wollenberger's research work on the biochemistry of cardiac ischaemia and the transient acceleration of glycogenolysis mainly brought about by GP activation.