Tissue release of cardiac markers: From physiology to clinical applications

The early release of cardiac markers is influenced by a variety of factors, the most important influence being their intracellular compartmentation. I n contrast to the release of cytosolic proteins, the release of structurall y bound proteins requires both a leaky plasma membrane and a dissociation o r degradation of the subcellular structure, which is a slower process. Anot her major impact is the susceptibility to the degradation by cytosolic prot eases, such as the calpains. The lysosomes are stable within the first 3-4 hours after onset of ischemia, and, therefore, their enzymes are not involv ed in the early degradation of structurally bound proteins. Troponin I and troponin T are substrates of CI-calpain. Current experimental as well as cl inical results suggest that the molecular mass seems to be of minor importa nce for the pattern of appearance of myocardial proteins in blood after myo cardial infarction. However, within the family of molecules with a certain intracellular compartmentation, the molecular mass is an influence on the a ppearance in blood, because heavier molecules diffuse at a slower rate, and particularly smaller molecules, such as myoglobin, may enter the vascular system to an even larger extent directly via the microvascular endothelium. The higher the concentration gradient of a marker between the cardiomyocyt es and the interstitial space, the faster a parameter will translocate from sarcoplasma to the interstitial space as soon as the plasma membrane perme ability is increased. Another influence is local blood and lymphatic flow. Recent experimental studies showed that reperfusion causes a true accelerat ion of cellular protein leakage by an acute manifestation of plasmalemmal d isruptions and not just an enhanced wash out. Marker protein time-courses a fter myocardial damage are also markedly influenced by their disappearance rate from blood. Most proteins appear to be catabolized in organs with a hi gh metabolic rate, such as liver, pancreas, kidneys, and the reticuloendoth elial system. Smaller molecules, such as myoglobin, also pass the glomerula r membranes of the kidneys and are reabsorbed and subsequently metabolized in tubular epithelial cells.