Plasminogen- 125 I responses in dogs to a single injection of urokinase and typhoid vaccine and to vascular injury.

In vivo plasminogen responses to various stimuli were studied. Plasminogen-(125)I was prepared and used first for metabolic studies of plasminogen in control dogs. The average results were: the plasma plasminogen, 29.3+/-4.1 (SD) mg/kg; the interstitial plasminogen, 8.79+/-4.47 (SD) mg/kg; the half-life of plasma plasminogen-(125)I, 2.81+/-0.24 (SD) days; the fractional direct catabolic rate of plasminogen (j(3)), 0.295 day(-1); and the catabolic (synthetic) rate of plasminogen, 8.61+/-1.35 (SD) mg/kg per day. Studies were then made of the plasminogen-(125)I responses in dogs to a single injection of urokinase (A) and typhoid vaccine (B), and to vascular injury (C), which was produced by the damage of venous endothelium by a phenol injection. Effects of heparin were also studied in dogs given the phenol injection (D). Disc electrophoretic analysis of plasma showed generation of plasmin-(125)I in all except the control experiments. The duration of plasmin-(125)I generation was about 6 hr in A, 6 hr in B, and at least 5 days in C. Heparinization (D) shortened the duration of generation to about 6 hr. For further quantitative analysis of the tracer data, a model for coexistent plasminogen-(125)I and plasmin-(125)I was proposed and validated, from which some new analytical methods were derived. Using these methods, the average fractional rate of plasmin-(125)I generation from plasminogen-(125)I (j(4)) was 0.41 day(-1) in A, 0.30 day(-1) in B, 0.324 day(-1) in C, and 0.382 day(-1) in D. Further mathematical consideration showed that j(3) was zero at least in C during plasmin generation. Plasminogen synthesis was unchanged in all experiments. The average fractional breakdown rate of plasmin-(125)I (j(5)) in A, B, C, and D was 1.19, 1.13, 1.35, and 1.11 day(-1), respectively, and were closely similar. These results indicate that under normal conditions a major portion of plasminogen is directly catabolized without the formation of plasmin, but that significant amounts of plasmin were generated under the conditions described, that the normal process of direct breakdown of plasminogen is abolished during plasmin generation at least in C, and that the potential value of j(5) determination should be further explored.