Biomedical subjects
Publications and source records attributed to E Amundsen.
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Components of the plasma kallikrein-kinin system were determined in plasma samples from ten healthy subjects and eight patients with septic shock. Five of the patients died. Low levels of Hageman factor, prekallikrein, and high molecular weight kininogen, together with significantly reduced concentrations of alpha 2-macroglobulin, were observed during septic shock both in patients who died and in the survivors. The patients who died also revealed a pronounced reduction of functional kallikrein inhibition determined by a chromogenic peptide substrate assay. In the survivors, however, functional kallikrein inhibition was very well preserved during septic shock, being within the range of values found in normals. Also plasma prekallikrein and C1-esterase inhibitor levels were slightly higher in the survivors than in those who died. Our results confirm that the plasma kallikrein-kinin system becomes activated during septicemia and that consumption of components of this protease system occurs. Because both C1-esterase inhibitor concentrations and functional kallikrein inhibitory activities were higher in patients who survived septic shock than in the fatal cases, our results suggest that functional inhibition of plasma kallikrein appears to play a major role in the outcome of this condition.
Components of the fibrinolytic system including functional activities of plasma antiplasmins were studied in experimental lung-insufficiency in a canine model. The procedure included hemorrhagic hypotension for 2 hours and occlusion of the hepatic artery, portal vein and common bile duct for 20 minutes of the hypotensive period. Plasma levels of plasminogen decreased gradually during the experiments. Using chromogenic peptide substrate assays, significant reductions of both "immediate" and "time dependent" antiplasmin activities were observed during the first few hours of the experiments. After 4 hours, both antiplasmin activities gradually increased. In 2 of the animals studied "time dependent" antiplasmin activities were 113 and 118 per cent of initial values at 12 hours. These findings emphasize that increased antiplasmin activities may be of great importance for fibrin deposition, leading to a state of microembolism in the lung in this condition.
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Thromboembolism of minor vessels in the lungs is almost constantly seen in posttraumtic lung insufficiency. Many investigators consider it as the primary factor in the pathogenesis of this condition. The present paper deals with screening of the coagulation system as part of a more extended project also investigating changes in the fibrinolytic system and the kallikrein-kinin system. The data are also to be compared with morphological findings during the development of experimental posttraumatic lung insufficiency. The experimental syndrome was evoked in Labrador retriever dogs by haemorrhagic hypotension combined with clamping of the portal triad. The surgical procedure was extended to additional thoracotomy in one group of dogs. Group I, without thoracotomy, were followed for 12 hours. Group II, with thoracotomy, were followed until they succumbed (3-14 hours). Thrombotest (TT) showed a steady prolongation of clotting time in both groups, whereas Cephotest did not reveal any alterations, except for a significant prolongation in group II just before collapse. Fibrinogen was markedly reduced in both groups. Platelets and leucocytes were significantly reduced, but only in group II. It is concluded that the present data are indicative of disseminated intravascular coagulation. The involvement of the intrinsic coagulation system is questioned.
During approximately the past 20 years a new syndrome has become the focus of interest for people who treat injured patients. It is characteristic of this syndrome that patients who have been exposed to extra-thoracic injury may succumb to pulmonary insufficiency, even though their primary injury has been properly corrected. This syndrome has been briefly mentioned in the literature before, but the first detailed description was given by Jenkins and co-workers in 1950. It was, however, the Vietnam war that provided the main impetus for research in this area. During this war the Americans took both infusion therapy and respiratory therapy to the frontlines. Many injured soldiers who would otherwise have died due to their injury, now survived the initial trauma. One then found that even if the trauma were properly corrected, many patients succumbed to pulmonary insufficiency a few days later.
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A chromogenic peptide substrate H-D-Val-Leu-Arg-pNA (S-2266) has been used for the determination of glandular kallikrein derived from pancreas, urine and saliva. The conditions used have been optimized. The methods developed are simple and shown to have good reproducibility.
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The effects of extreme hemodilution and open heart surgery on antiplasmin and plasmin activities were investigated in dogs. Assays for plasmin and antiplasmin activities were performed with a chromogenic peptide substrate for plasmin. After hemodilution and during cardiopulmonary bypass (CPB), plasmin activity on the substrate was observed and levels of both "fast-reacting" and "total" antiplasmins fell. The plasmin activity was shown to be due to the formation of alpha2-macroglobulin-plasmin complex which exhibited amidolytic activity on the chromogenic substrate. The falls in antiplasmin activity together with the appearance of the alpha2-macroglobulin-plasmin complex revealed that activation of the fibrinolytic system had occurred. After the operation and following reinfusion of autologous blood, decreased plasmin and increased antiplasmin activities were observed. On the first and sixth days following the operation plasmin activities were still slightly higher than pre-operation values, whilst antiplasmin activities were normal.
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Endotoxin shock (ES) was induced in Labrador retriever dogs by infusion of a lethal dose of Escherichia coli endotoxin. Spontaneous plasma kallikrein activity and prekallikrein levels were determined during subsequent stages of the shock both by an esterolytic assay (BAEe) and a new amidolytic assay utilizing a chromogenic tripeptide derivative (Chromozym PK, Prntapharm AG, Basel Switzerland). During the late stages of shock characterized by a substantial decline of blood pressure, plasma prekallikrein levels determined by the amidolytic assay were considerably reduced. In this phase of the shock both the esterolytic and the amidolytic assays revealed a significant elevation of spontaneous activity. Plasma prekallikrein determined by the esterolytic assay was found to be elevated vs. control values for the whole duration of ES. The findings made seem to associate activation of the plasma kallikrein-kinin system to the circulatory collapse of endotoxin shock in dogs.
Antiplasmin activity was studied during various stages of lethal canine endotoxin shock by means of assays utilizing a new chromogenic tripeptide derivative (S-2251 AB Kabi Peptide Research Division, Mölndal, Sweden). By applying a preincubation time of 30 sec and 5 min, respectively, 'immediate' and 'time-dependent' antiplasmin activities were determined. During shock gradually decreasing values of 'immediate' antiplasmin activity was observed. 'Time-dependent' antiplasmin activity also revealed a decreasing pattern, these changes, however, were less pronounced when compared with 'immediate' antiplasmin activity. The changes of plasma antiplasmin activities observed were accompanied by decreasing values of plasminogen and evidence of plasmin activity. alpha-Antitrypsin and alpha2-Macroglobulin quantitated with electroimmunoassay technique also revealed decreasing patterns during shock.
Plasma levels of prekallikrein, kallikrein, high molecular weight kininogen and kallikrein inhibitors were measured in samples from dogs infused with E. coli endotoxin. Markedly reduced levels of prekallikrein and high molecular weight kininogen were seen at circulatory collapse and free kallikrein was detected. Both 'fast-reacting' and 'time-dependent' inhibitors of plasma kallikrein were significantly reduced. Fractionation of pre-infusion and collapse samples by gel filtration together with immunological procedures indicated that both alpha2-macroglobin and alpha1-antitrypsin were the major kallikrein inhibitors in dog plasma, and that they were significantly reduced in the collapse samples.
Spontaneous plasmin activity and 'fast-reacting' and 'time-dependent' antiplasmin activities were determined during various stages of canine endotoxin shock by means of assays utilizing a chromogenic tripeptide derivative (S-2251, Kabi AB, Peptide Research Division, Mölndal). During shock, gradually decreasing values of both antiplasmins were found, revealing most pronounced falls of 'fast-reactin' antiplasmin. These changes of plasma antiplasmin activities were accompanied by decreasing values of plasminogen and evidence of plasmin activity. Immunochemical determination of plasma levels of alpha2-macroglobulin (alpha2-M) and alpha1-antitrypsin (alpha1-AT) and gel filtration studies, demonstrated marked falls in levels of alpha2-M and alpha2-plasmin inhibitor and small reductions of alpha1-AT in this state.
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