Direct determination of distribution volume and disappearance rate of native creatine kinase in humans.
Distribution volume (DV) and disappearance rate (Kd) of native creatine kinase (CK), parameters needed for enzymatic estimation of infarct size, have not been characterized in humans. Values for these parameters have been determined in experimental models and extrapolated for use in humans. During hemodynamic monitoring, 100 to 150 ml of enzyme-rich plasma was collected from 10 patients with acute myocardial infarction, stored at -30 degrees C for a maximum of 6 days, and then rapidly reinfused back to the same patient after return of CK serum activity to baseline levels. After reinfusion, blood samples were obtained at 5- to 15-minute intervals for 2 hours and at 30- to 60-minute intervals for an additional 10 hours. In each specimen, total CK activity and MM-CK and MB-CK concentrations were determined by spectrophotometry and radioimmunoassay. Data were analyzed by either nonlinear least-squares approximation or the noncompartmental approach after baseline subtraction. Concentration of immunologically active molecules appeared to decline in parallel to enzymatic activity. In three patients a double exponential decay was demonstrated. All others exhibited single exponential decay, with a Kd of 0.0023 +/- 0.00057 (SD) min-1. DV averaged 3284 +/- 693 (SD) ml, 5% of body weight. There was no correlation between Kd estimated from terminal portions of CK time-activity curves following infarction and Kd calculated after reinfused plasma. It was concluded that a one-compartment model using values for Kd and a DV compatible with plasma volume is suitable for clinical application, and that true Kd cannot be determined from the terminal portion of CK time-activity curves after acute infarction.
D001804:Blood Transfusion, Autologous; D001835:Body Weight; D003402:Creatine Kinase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D009203:Myocardial Infarction / Q000201:enzymology*; D010953:Plasma Volume; D013997:Time Factors; D014018:Tissue Distribution
D007527:Isoenzymes; D003402:Creatine Kinase