Abstract
In our previous studies, UK injected into the general circulation was found to lose its activity very rapidly. The rate constant of such UK inactivation is defined as the inactivation rate constant of UK. Although the value of this inactivation rate constant can be calculated by compartment analysis, its nature and significance remain unclear. The present study was therefore undertaken to clarify the factors which affect the inactivation rate constant of UK.
When the UK solution was injected into the peripheral vein of normal rabbits, the fibrinolytic activity of the plasma showed a rapid decrease, as reported previously. There was marked fibrinolytic activity at 30sec to 1min, slight fibrinolytic activity at 3min, and almost no fibrinolytic activity at 5-6min after the UK injection. When UK solution was injected into the portal vein of the normal rabbits, no detectable fibrinolytic activity developed in the plasma.
When the UK solution was injected into the peripheral vein first, and injected again into the portal vein about one hour later, the fibrinolytic activity of the plasma was markedly enhanced at the second injection, and was remained even at 10min after the injection of UK solution.
When the UK solution was injected into the peripheral vein of rabbits whose liver, spleen and kidneys had been isolated from the general circulation, the fibrinolytic activity of the plasma was marked and sustained for a long period. The half time of decay of fibrinolytic activity obtained from the calibration curve was 4.24±0.98min (mean±standard deviation, n=5). This value is significantly greater than that for UK injection into the peripheral vein of normal rabbits (0.95±0.37, n=5) (p<0.005).
These results suggest that the reticuloendothelial system (RES) plays an important role in UK metabolism, so that the inactivation rate constant of UK may derive largely from the activity of the RES.
