Selection of a suitable circulatory model for the plasma clearance and distribution of cardiac enzymes in the dog

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Abstract
This study concerns the existing controversy about the validity of one-vs two-compartment models for the distribution of intravenously injected enzymes in the dog. It is shown that infusion of enzyme at a constant rate permits direct calculation of enzyme clearance constants, independently of the specific model used. Enzyme preparations were obtained by leakage of enzymes from heart tissue under hypoxic conditions. The values for the plasma clearance constants k of creatine kinase (CK) and aspartate aminotransferase (AST) are 0.36 ± 0.030 h−1 and 0.21 ± 0.014 h−1 respectively (mean ± SE, n = 8). These values are compared with clearance rates as estimated from a bolus injection of enzyme given 90 min before the infusion was started. For both enzymes the values of k as estimated from the infusion equal the apparent disappearance constants kd obtained from the preceding bolus injections. From these experiments it is concluded that plasma clearance of CK and AST is adequately described by a one-compartment model. In 10 experiments plasma clearance curves after bolus injections were sampled over 8 h. Disappearance of AST was strictly mono-exponential, while for CK a slight biphasic effect was observed in five out of ten cases resulting into improved double-exponential fits. It is concluded that this effect is not due to exchange of enzyme with an extravascular pool but is caused by a fraction of enzyme with a slightly higher elimination rate. This phenomenon is illustrated by showing that AST also shows biphasic disappearance upon injection of an enzyme preparation obtained by mechanical disruption of cells. Individual and day-to-day variations in k values obtained for CK and AST do not show any correlation. This suggests independent clearance mechanisms for both enzymes.

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