Use of Serum Markers to Measure Acute Myocardial Infarct Size: Lessons of a Nonlinear Dynamical Model

During acute myocardial infarction, dying cells in the myocardium release a number of chemicals that appear in the blood stream. By sampling the blood and assaying for these markers at intervals after infarction, we obtain a measure of the amount of myocardium lost, and the area under the marker concentration curve with time has been used to estimate the size of infarct. Because many of the important variables in this system are impossible to measure in patients and difficult to measure or control in experimental animals, simulations using a mathematical model provide an important way to learn about the infarct–marker relationship. This paper described a nonlinear dynamical model that allows for continuous changes in coronary flow as well as five key parameters during acute infarction. These five include amount of marker available for release from the myocardium, relative rate of release of marker from the myocardium, rate of degradation of marker in the myocardium, plasma volume, and relative rate of loss of marker from the plasma. By varying these five together with infract size, simulations using the model demonstrate a noisy relationship between infarct size and area under the plasma marker curve. Mathematically, this noise implies that there is not a one-to-one mapping from marker curve to infarct size, and we should expect no more than a statistical mapping that fails to resolve all the uncertainty. The results do suggest that early reperfusion should reduce, rather than increase the noise in this relationship.