Leukocyte neutral proteinase inhibitor of the pig: modification by eglin C and superoxide dismutase of the response to shock.
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Animals↗
Biomedical subjects
M Siebeck
Publications and source records attributed to M Siebeck.
Endotoxin shock in the rat: reduction of arterial blood pressure fall by the bradykinin antagonist B4148.
The selective competitive bradykinin (BK) antagonist (B4148) produced significant inhibition of the hypotensive effect of BK in rats. Using a rat model of endotoxin shock, the fall in mean arterial blood pressure to an intravenous injection of lipopolysaccharide from E. coli was significantly attenuated by the B4148 as compared to controls. These findings suggest that kinins are involved in the hypotensive response to endotoxin shock in rats. The development of potent BK antagonists offers a new experimental approach for evaluating the role of kinins in this and other disease states.
Animals↗
Therapeutic effects of the combination of two proteinase inhibitors in endotoxin shock of the pig.
Thrombin activation is an important underlying pathomechanism for septic organ failure. The selective thrombin inhibitor, hirudin, reduces the endotoxin-induced fibrinogen consumption and thus the formation of fibrin monomer, as well as the pulmonary vasoconstriction in pigs at plasma concentrations of 70 to 100 nmol/l. PMN cell activation with subsequent release of digestive proteases is in part responsible for the loss of fluid and protein from the vascular compartment during septic shock. Administration of the inhibitor of PMN elastase, cathepsin G and mast cell chymase, eglin C, reduces the loss of intravascular protein during the first 4 hours of endotoxin shock at plasma concentrations in the range of 2 mumol/l.
Animals↗
PMN elastase and leukocyte neutral proteinase inhibitor (LNPI) from granulocytes as inflammation markers in experimental-septicemia.
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Animals↗
[Early phase of healing of anastomoses with special reference to peritonitis and ischemia].
Experimental sutureless colonic anastomosis was evaluated under various conditions during the first 24 postoperative hours. Adaptation of large bowel segments was achieved by interrupted inverting sutures, which were removed after one hour. This short adaptation period was sufficient for fibrinous contact of bowel segments. Breaking strength of intestinal anastomosis was determined under normal conditions, in peritonitis, complete ischemia and unilateral ischemia of one bowel segment. As control parameter breaking strength of conventional anastomosis was determined under normal conditions. We obtained the following results: 1) Sutureless anastomosis exhibited significantly lower breaking strength than conventional anastomosis. 2) Sutureless anastomosis showed a significant increase in breaking strength under normal conditions after the first 6 h, on the contrary breaking strength remained at lower levels in peritonitis. 3) In complete ischemia anastomotic failure was observed even after 3 h of adaptation. Therefore breaking strength was not measurable. 4) Under unilateral ischemia breaking strength of intestinal anastomosis was significantly lower than under normal conditions.
Anastomosis, Surgical↗
Attenuation of arterial blood pressure fall in endotoxin shock in the rat using the competitive bradykinin antagonist Lys-Lys-[Hyp2, Thi5,8, DPhe7]-Bk (B4148).
The selective competitive bradykinin (Bk) antagonist, B4148 (Lys-Lys-[Hyp2, Thi5,8, DPhe7]-Bk) infused at 100 micrograms kg-1 min-1 into rats produced a significant inhibition of the hypotensive effect of Bk and had no effect against acetylcholine-induced responses. In a rat model of endotoxin shock, the fall in mean arterial blood pressure in response to an intravenous injection of lipopolysaccharide from E. coli was significantly attenuated by the same infusion of B4148 compared to controls. These findings suggest that kinins are involved in the hypotensive response to endotoxin shock in rats. The development of potent Bk antagonists offers a new experimental approach for evaluating the role of kinins in this and other disease states and potential therapy in such disorders.
Animals↗
Determination of leukocyte elastase-inhibitor complexes and leukocyte neutral proteinase inhibitor by enzyme immunoassays. Leukocyte elastase-inhibitor complexes in porcine blood, III.
Sensitive enzyme immunoassays for the determination of total leukocyte neutral proteinase inhibitor and polymorphonuclear elastase-leukocyte neutral proteinase inhibitor complexes are described. The usable ranges of the standard curves were from 80 ng/l to 10 micrograms/l. The relative intra-assay coefficients of variation of the tests were between 2 and 4%, and the inter-assay coefficients of variation between 4 and 10%. In vitro and in vivo studies were performed with septic pigs and isolated leukocytes. The results show that leukocyte neutral proteinase inhibitor can be used in pigs as a parameter for the development of a septicaemia.
Animals↗
Pharmacokinetics and pharmacodynamics of hirudin in man after single subcutaneous and intravenous bolus administration.
The pharmacokinetics (half-life time of absorption and elimination, total clearance, distribution volume etc.), effects on hemostasis (clotting times, blood cell counts) and renal excretion of hirudin were investigated on healthy volunteers after single subcutaneous (600, 800 or 1000 antithrombin units (AT-U)/kg; n = 3 per each dose) or intravenous (1000 AT-U/kg; n = 3) injections. Hirudin concentrations in citrated plasma and urine were determined by means of a radioimmunobioassay, whereby the inhibitor is detected by its thrombin binding capacity. Plasma profiles were adequately described by the Bateman equation (subcutaneous injection) and by an open two-compartment model (intravenous injection), respectively. Within 24 h about half of the applied hirudin dose was renally excreted in active form. The prolongation of clotting times (thrombin time, partial thromboplastin time (PTT), Quick) was dependent on the hirudin plasma level. The PTT proved to be the most reliable test for representation of the actual inhibitor plasma concentrations. Generally, the blood cell counts were unchanged by the hirudin administration. All test subjects tolerated the hirudin injection without visible or measurable side effects.
Adult↗
Influence of the lysosomal elastase inhibitor eglin on the development of interstitial lung edema in E. coli bacteremia in pigs.
Infusion of 3 X 10(10) live E. coli cells into anesthetized piglets induced severe septicemia with characteristic alterations in systemic and pulmonary circulation, lung function and morphology, blood cell counts and plasma protein composition. The simultaneous infusion of the elastase-cathepsin G inhibitor, r-eglin c, in a doses of 3.85 mg/kg X h for 4 hrs, reduced mortality, plasma protein consumption, and accumulation of interstitial fluid in the lungs. These findings are in favour of the concept that during septicemia the balance between liberated lysosomal proteinases and their extracellular inhibitors is severely disturbed. It can be at least partially restored by administration of an exogenous elastase inhibitor.
Animals↗
Evaluation of the kinin-induced pathomechanisms in the development of ARDS by kallikrein inhibition in vivo.
Our findings indicate that the kallikrein-kinin system might participate in the development of acute respiratory failure. They were assessed by measurements of plasma kininogen levels, blood pressure recordings and lung morphology. Aprotinin plasma concentrations ranging from 4 to 7 KIU/ml proved sufficient to inhibit effectively the hemodynamic and morphologic effects caused by tissue kallikrein infusion.
Animals↗
C1-esterase inhibitor in early septicemia.
In bacteremic pigs, both administered human C1INH and endogenous C1INH lost inhibitory activity. In septic pigs which received human C1INH a difference between immunologically determined concentration and inhibitory activity of C1INH became apparent. In animals which survived at least 24 hrs the C1INH activity showed an acute phase response. In a model of E. coli bacteremia in weaned pigs administration of human C1INH showed protective effects on lung capillary permeability as well as less leucocytosis.
Animals↗
Effect of aprotinin and C1-esterase inhibitor on activation of the plasma kallikrein-kinin system in vivo.
Infusion of dextran sulfate in pigs rapidly activates the intrinsic cascade of the coagulation system including plasma prokallikrein and leads to release of kinin by limited proteolysis of kininogen. In this model, strong suppression of the DXS-induced activation of the plasma kallikrein-kinin system is seen at plasma aprotinin levels above 400 KIU/ml and C1INH levels above 4 U/ml.
Animals↗
Granulocyte elastase and white cell counts in septic pigs.
Our data are consistent with the assumption that in early septicemia polymorphonuclear granulocytes are sequestered and release lysosomal elastase locally into the respiratory tract and into the circulation.
Animals↗
[Indications and results of caval filter operation using the Kimray-Greenfield filter].
Recurrent pulmonary embolism is a permanent risk. The caval filter is able to prevent embolism. The implantation can be done even in seriously ill patients under local anesthesia. In our patients no complication or recurrent embolism were observed. Only one case developed a thrombotic occlusion of the Kimray Greenfield filter as a result of retroperitoneal carcinosis. The relapse of embolism was prevented by the filter. All other implants were seen patent in the digital subtraction angiography.
Filtration↗