PHYSIOLOGICAL MODELING OF SERUM CREATINE-KINASE KINETICS AFTER MYOCARDIAL-INFARCTION

Several procedures have been proposed for using serum enzyme curves to estimate infarct size after acute myocardial infarction. If reliable, these procedures would obviously be useful in prognosis and in trials to evaluate the effectiveness of different interventions directed to reducing infarct size. However, there are limitations in the existing methodologies and in the present study three compartmental models were investigated for suitability using creatine kinase (CK) data from 127 patients. The best model was a function with four parameters; k, the rate of release of CK from the myocardium; A1, max, the maximum amount of CK released from the myocardium to each milliliter of serum; tl, the lag time correcting for the delay between infarct time and the first sample; and kel, the elimination rate constant from serum. The model was better than earlier models in explaining total variation in data (R2 > 0.9 in 114 of 127 cases); residual distributions were acceptable and parameter estimates were reproducible. With this approach, parameters have more biological meaning than those derived from earlier empirical functions. It is suggested that k represents the rate and A1, max the extent of myocardial necrosis. A clinical trial using this model to assess the merit of a given therapy would look for changes in k and A1, max as measures of effectiveness. © 1979.