Kinetics of myoglobin release and prediction of myocardial myoglobin depletion after coronary artery reperfusion

Abstract

To better define the usefulness of blood myoglobin measurements in evaluating the effectiveness of attempted thrombolysis, we studied the kinetics of myoglobin entry into and removal from the circulation after coronary artery reperfusion and the relation between directly measured depletion of myocardial myoglobin after coronary occlusion and reperfusion and the amount of depletion predicted from plasma myoglobin concentration-time curves. Initially, canine myoglobin was administered to 11 dogs by both bolus injection and 40-minute infusion, and the subsequent disappearance patterns of myoglobin from plasma monitored by radioimmunoassay. A monoexponential regression line (corresponding to a one-compartment model) and a biexponential regression line (corresponding to a two-compartment model) were determined for each set of washout data, the kinetic parameters were calculated, and the goodness of fit of each model was assessed. Results were similar after both methods of myoglobin administration. In five of 11 animals, the one-compartment model described the myoglobin kinetics better; in the other six animals, the two-compartment model was statistically superior, but values for the volume of distribution and elimination rate constant differed by only 10% from the one-compartment estimates. After bolus administration of myoglobin and with a one-compartment model, the volume of distribution of myoglobin was determined to be 1,601 ± 77 (SEM) ml, representing 6.8 ± 0.2% of total body weight; the elimination rate constant averaged 0.132 ± 0.006/min and corresponded to a mean half-life of disappearance of 5.5 ± 0.2 minutes. In 16 additional animals undergoing a 2-hour occlusion and 4-hour reperfusion period of the mid left anterior descending coronary artery, myoglobin was rapidly released from the injured myocardium, with peak rate of myoglobin release occurring within 50 minutes of onset of reperfusion. The pattern of myoglobin release into the circulation was discontinuous ('staccato phenomenon') and persisted throughout the entire reperfusion period with 16% of total myoglobin release occurring after 2 hours. In 12 animals, the amount of myoglobin predicted by the one-compartment model to have entered the circulation was compared with directly measured myocardial myoglobin depletion that varied from 5 to 117 mg. The correlation coefficient for the relation (y = 1.2 x -14.5) was 0.97 (p < 0.01).