Estimation of the fractional catabolic rate constants for the elimination of cytosolic liver enzymes from plasma.

Pathological elevations of the plasma activities of liver enzymes are not simply related to the quantitative release of such enzymes from the liver. Several enzymatic indices, such as the well-known de Ritis quotient, may be determined by differences in the time course of hepatic enzyme release, rather than reflecting true differences in the released quantities of various enzymes. A more quantitative use of enzymatic data is hampered by the fact that the fractional catabolic rate constants for the elimination of enzyme activities from plasma are unknown. In the present study, three of these constants are estimated by comparison of the time-activity curves in plasma with the corresponding curve of a simultaneously released, more slowly eliminated reference enzyme. This method can be applied in patients with an acute short period of hepatic enzyme release. Values obtained for the cytosolic isoforms of lactate dehydrogenase, AST and ALT are: fractional catabolic rate constant (lactate dehydrogenase isoenzyme 5) = 0.13 +/- 0.01 hr-1, fractional catabolic rate constant (cytosolic AST) = 0.088 +/- 0.016 hr-1 and fractional catabolic rate constant (cytosolic ALT) = 0.034 +/- 0.004 hr-1 (mean +/- S.E., n = 10). These values are much higher than the apparent disappearance rate constants, because of extravascular return of activity and tailing release of enzymes during the major part of the elimination phase. It is shown that these results are consistent with earlier published data on the disappearance rates from plasma of lactate dehydrogenase, AST and ALT after acute liver injury. Cumulative release of various cytosolic enzymes occurred in proportion to the corresponding activities in human control livers.

Greater than expected alanine aminotransferase activities in plasma and in hearts of patients with acute myocardial infarction.

Early increases in the activity of alanine aminotransferase (ALT, EC 2.6.1.2) in plasma are observed in about 7% of patients with acute myocardial infarction (AMI), of whom about half die. Some type of liver injury, secondary to AMI, could be responsible for this phenomenon. However, quantitative analysis shows that the release of ALT in most of these patients conforms to the myocardial release pattern. Moreover, extra release of hepatic aspartate aminotransferase (EC 2.6.1.1) is not observed. These findings suggest that the heart may occasionally contain a high ALT activity. This hypothesis was verified by determination of enzyme activities in 10 hearts obtained from patients who died after AMI. The mean ALT activity in these hearts, 21 (SD 12) U per gram wet weight, significantly (P less than 0.01) exceeds the value of 7.7 (SD 4.9) U/g found for seven control hearts and may reflect increased amino acid metabolism in the energy-depleted heart muscle, as described earlier for skeletal muscle.

The accurate control of ultrafiltration.

An apparatus has been contructed to regulate ultrafiltration accurately during dialysis. The principle of the apparatus is that, per unit of time, exactly the same amount of dialysate is introduced into the dialyzer as is discharged from it. The apparatus consists of two isovolumetric pumps connected in line. The four compartments of the two pumps must change their functions at every pump stroke. This is a accomplished by a switching system. There is a continuously closed dialysate circuit. The fluid extracted from this circuit will be replenished from the blood compartment of the dialyzer. Ultrafiltration is regulated by a simple peristaltic pump, which sucks the fluid out of the closed dialysate circuit. The isovolumetric pumps and the switching system are driven by the elevated pressure of the dialysate (0.5--1.0 atm). The apparatus can be used in single pass dialysis. Dialysis in accordance with the Bergström principle can be simply performed. In over 5,000 dialyses with several types of dialyzers, ultrafiltration was always accurate within the measuring limits. Considerable improvement was noticed in the well-being of the patients; hypotension, nausea, vomiting and muscle cramps were not seen.