Myoglobin

Myoglobin is an intracellular heme protein that aids in the transport of oxygen. Oxygen binds to the porphyrin ring of myoglobin, as it does to hemoglobin, forming oxymyoglobin. Myoglobin is abundantly present in both cardiac and skeletal muscle.

Immunoassays detecting serum levels of myoglobin have long been used to confirm the diagnosis of myocardial infarction (MI). At approximately 17,500 Da, myoglobin is small enough to pass easily into circulation after cardiac injury, making it one of the earliest biochemical markers of MI. Serum myoglobin levels peak at approximately 6 to 9 hours post-MI, but return to normal within 24 to 36 hours as myoglobin is easily and rapidly cleared from circulation

Myoglobin Background Information...

Myoglobin is a globular, iron-containing protein that serves primarily to store and transport oxygen in cardiac and skeletal muscle. It is single polypeptide chain consisting of 153 amino acids with a molecular weight of 16.7-17.7 kDa. Both tissue forms are encoded by the same gene, but at least five genetic variants are known to exist. (1) In addition, cardiac and skeletal myoglobin undergo significant post-translational modification, contributing to their isoform diversity. The hydrophilic surface residues render it water-soluble, while its hydrophobic core allows the reversible binding and storage of oxygen. Upon muscle contraction, cytosolic myoglobin reaches a deoxygenated state within 20-40 seconds, suggesting it provides its oxygen for mitochondrial consumption. In addition, myoglobin exhibits nitric oxide (NO) activity and nitrite reductase activity, both of which function to regulate mitochondrial activity during muscle use.

In clinical diagnostics, serum assays for myoglobin are instrumental in assessing muscle damage in cardiovascular and critical care applications. Its small size facilitates passage into circulation shortly after acute muscle injury. Upon myocardial infarction (MI), myoglobin is detectable in serum as early as 30 minutes to 1 hour after the onset of symptoms. Myoglobin levels peak at approximately 6-12 hours, before being cleared from circulation by the kidneys and returning to normal within 24 hours. This rapid clearance imparts value to myoglobin in cardiovascular diagnostics.

Myoglobin is not heart-tissue specific, so it is not recommended to diagnose acute coronary syndromes like unstable angina, myocardial injury, and MI. Assays for the cardiac forms of troponin I (TnI) and troponin T (TnT) are far more sensitive and specific for acute coronary events. Myoglobin is, however, valuable in monitoring patients who have already experienced a recent cardiac event. Myoglobin clears from circulation in approximately 24 hours, while CK-MB remains elevated for 2-3 days and the troponin subunits can remain elevated for as long as 1-2 weeks. These release kinetics make myoglobin useful in detecting re-infarction in patients who have undergone a cardiac event.

With myoglobin levels returning to normal within 24 hours, new elevations can indicate myocardial damage from a subsequent cardiac event. Myoglobin assays exhibit >80% specificity in detecting a second ischemic episode, but that specificity increases to >95% when combined with the tending physician’s assessment of the patient. (2) Myoglobin is also useful in emergency room and first-response settings. When combined with TnI or TnT, myoglobin assays are exceptional at ruling-out MI. The negative predictive value using both biomarkers together is 99.6%. (3) In addition, when two consecutive measurements of myoglobin alone are taken 2-3 hours apart and the levels remain normal, myoglobin assays alone reach 97% accuracy in ruling-out MI. (4,5)

Beyond its cardiovascular utility, myoglobin assays aid in the diagnosis of rhabdomyolysis and acute compartment syndrome. Also, myoglobin serum levels help to assess severity and determine the course of treatment for muscle damage due to crush and major trauma injuries. More recently, clinical utility for myoglobin assays has been shown in evaluating severity and predicting risk in sepsis and in monitoring post-sepsis syndrome. In addition, myoglobin is helpful in the risk stratification of patients with sepsis-induced cardiorenal syndrome and in assessing severity in COVID-19.

Myoglobin has been in clinical use in cardiovascular diagnostics since the 1970s. Although it is not heart tissue-specific, myoglobin continues to provide unique diagnostic data in cardiovascular care and beyond. It is no longer used in the diagnosis of MI, but its well-demonstrated utility in ruling-out MI and in predicting re-infarction in ACS patients assure its continued clinical relevance.

References
1. Gussoni, Scorciapino, Vezzoli, et al. Biochim Biophys Acta. 2011; 1814(12): 1919-1929.
2. Green, Skarbek-Borowski, Chan, et al. Acad Emer Med. 2000; 7(6): 625-636.
3. McCord, Nowak, McCullough, et al. Circ. 2001; 104(13): 1483-1488
4. Tucker, Collins, Anderson, et al. Ann Emerg Med. 1994; 24(4): 704-708
5. Gornall, Roth. Clin Biochem. 1996; 29(4): 379-384.