Search

Myocardial activities of several enzymes were measured in infarcted and non-infarcted areas of heart sections obtained from eight patients who died after acute myocardial infarction. Similar data were obtained from four patients with cardiovascular disorders who died from causes other than myocardial infarction and from six patients without previously known heart disease. It was found that both non-infarcted and infarcted tissue samples contained considerably altered enzyme activities. This finding explains the low correlations between enzymatic and histological estimates of infarct size previously reported. However, when the residual myocardial activities of different enzymes were compared with each other, a close correlation was found between creatine kinase, alpha-hydroxybutyrate dehydrogenase, and aspartate aminotransferase. It appears that the pathological changes in the myocardial activities of these enzymes may be explained by the phenomenon of diluted myocardium. This indicates that myocardial injury, as estimated from plasma enzyme activities, may still be expressed meaningfully in gram equivalents of healthy myocardium.

It is demonstrated that plasma elimination constants for rapidly eliminated circulating tissue enzymes can be obtained from plasma time-activity curves if a slowly eliminated reference enzyme is simultaneously sampled. Enzyme and reference enzyme must be released together into the plasma. From the elimination constants thus obtained enzyme release into the plasma can be calculated as a function of time. The method can be applied during continuous release of enzyme into the plasma. The validity of the method is tested in the dog by intravascular infusion of a preparation of cytoplasmic enzymes, obtained by incubating dog liver under anoxic conditions. Alanine aminotransferase (ALT) was used as reference enzyme. Infused quantities of aspartate aminotransferase (AST), glucosephosphate isomerase (GPI) and ALT can be estimated with coefficients of variation (CV) of respectively 10, 19 and 7.6%. Application of the method to plasma time-activity curves of enzymes in patients after acute myocardial infarction (AMI), with alpha-hydroxybutyrate dehydrogenase (HBD) as reference enzyme, results in the following values for the fractional catabolic rate constants (FCR) of AST, GPI, creatine kinase (CK) and its isoenzyme CK(MB): FCRAST = 0.093 +/- 0.006 h-1; FCRGPI = 0.27 +/ 0.03 h-1 (mean +/- SE, n = 14); FCRCK = 0.20 +/) 0.02 h-1 (n = 30); FCRCK(MB) = 0.34 +/- 0.08 h-1 (n = 16). These values are considerably higher than mentioned by most authors, and this indicates that enzyme release after AMI has been underestimated. After AMI, enzymes are released in quantities proportional to the enzyme content of human heart tissue. Average release of CK conforms to this rule but large variations for individual patients are observed. Accurate estimates of the quantities of enzymes released into the plasma can be made for slowly eliminated enzymes by the use of fixed mean values for elimination constants. The results presented to this study indicate that tissue enzymes released from infarcted myocardium in patients after AMI are recovered quantitatively in the plasma. Local inactivation of enzymes or inactivation during the transport from heart to plasma is not significant in such patients.

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.