Biochemical markers of ischemic injury.

Enzymatic estimation of infarct size entails assumptions requiring analysis and modification during evolution of the method. Myocardial creatine phosphokinase (CPK) depletion reflects infarct size under many experimental conditions, and release of CPK into the circulation has been correlated with histologically demonstrable necrosis. Use of a one compartment model relating serum CPK changes to myocardial CPK depletion is a simplification requiring estimates of CPK disappearance rate (kd) as one parameter. Conformity of kd to first order kinetics and its lack of variance despite marked hemodynamic perturbations, myocardial infarction per se, or successive daily determinations have been documented. In patients with myocardial infarction, enzymatic estimates of infarct size correlate with morbidity and mortality, functional cardiac impairment, severity of clinical manifestations, frequency of ventricular dysrhythmia, and morphologically estimated infarct size. Improved estimates result from MB CPK analyses which avoid difficulties due to noncardiac CPK in the circulation and from individualization of values of kd. The discriminant power of enzymatic estimates as an index of prognosis has been demonstrated by discriminant function analysis. Prediction of infarct size enzymatically requires additional assumptions and conventionally employs an empirical algorithm rather than a physiological, deterministic model. Although predictions can probably be improved by incorporation of parameters reflecting processes governing CPK release and disappearance, the need for a prolonged interval during which observations are required prior to prediction limit the applicability of this approach to evaluation of therapeutic interventions whose effects are likely to be maximum when early implementation is possible.