RESUMEN
Five healthy volunteers were injected intravenously with 73-90 uCi purified human 131I-Antithrombin III (AT III), specific biological activity 5.6 U/mg. The tracer data were analysed using a three compartment model. The plasma radioactivity half life was 66.2 +/- 1.2 (sem) h, the fractional catabolic rate constant of the plasma pool was 0.025 +/- 0.002 (sem) h-1. These data were comparable with those described in the literature. Because of the difficulty in translating the mathematical analysis of various compartments into the biological model, biodistribution was monitored by a gamma camera linked to a DEC PDP 11/34 computer system. Dynamic and static images were obtained at fixed time intervals following the injection of 131I-AT III. Whole body scanning at intervals between the time of injection (t = 0) and t = 24.5 h showed 131I-AT III distribution over the heart, lungs, liver, spleen and great vessels. Dynamic scanning was performed over the heart, spleen and liver. Overlayed frames in the first ten minutes after the 131I-AT III injection showed the following radioactivity expressed as percentage of the injected dose; 5.9% +/- 0.3 (sem) over the heart, 10.6% +/- 0.9 (sem) over the liver and 1.1% +/- 0.1 (sem) over the spleen. A slower decline of the radioactivity between t = 0 and t = 24 h; (19%) was measured over the liver compared with the radioactivity disappearance over the heart region. This shows, in combination with the fact that the radioactivity disappearance over the heart was identical with the radioactivity decline measured in the plasma samples that retention of 131I-AT III occurred in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antitrombina III/metabolismo , Semivida , Humanos , Cinética , Hígado/metabolismo , Modelos Biológicos , Miocardio/metabolismo , Bazo/metabolismo , Distribución TisularRESUMEN
An 81-year-old male with a mild life-long bleeding history and an alpha 2-antiplasmin (alpha 2-AP) plasma level of 55% biological activity and 41% antigen activity (normal range 80-140%) was studied. The ratio of plasminogen binding (PB):non-plasminogen binding (NPB) alpha 2-AP assayed by modified crossed immunoelectrophoresis (CIE) was 7.3/2.7 (controls 6.3 +/- 0.49 SD/3.7 +/- 0.49 SD). The patient's alpha 2-AP showed decreased affinity for fibrin, i.e. 8.3% versus 32.4% of normal control alpha 2-AP associated with fibrin during clotting of plasma. A metabolic study performed with human purified 125I-alpha 2-AP (PB/NPB 7.7/2.3) showed a plasma radioactivity disappearance half-life of 72.9 h (n 60.1 +/- 5.3 h) with a normal fractional catabolic rate and a reduced absolute catabolic (synthetic) rate of 0.70 mg/kg/day (n 2.10 +/- 0.60 mg/kg/day). The exchange between the central and third compartment was increased. The increased alpha 2-AP PB form and the increased plasma radioactivity disappearance half-life are suggestive of a slower conversion of the PB form into the NPB form and/or slower degradation of the PB form. The bleeding tendency in this patient could be explained by decreased synthesis of alpha 2-AP and decreased binding to fibrin.