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Biomedical subjects

M Spannagl

Publications and source records attributed to M Spannagl.

At least 73 records · Page 4Linked to original sources
PubMed1994

Dextran sulfate activates contact system and mediates arterial hypotension via B2 kinin receptors.

To define some of the mechanisms underlying dextran sulfate (DXS)-induced hypotension, we investigated the effects of either the plasma kallikrein inhibitor des-Pro2-[Arg15] aprotinin (BAY x 4620) or the specific bradykinin B2-receptor antagonist Hoe-140 on the hypotensive response to DXS. In the first study, anesthetized miniature pigs were given DXS alone, DXS plus BAY x 4620 in various doses, or saline. As expected, DXS alone produced a profound but transient systemic arterial hypotension with a concomitant reduction in kininogen. Circulating kinin levels, complement fragment des-Arg-C3a, and fibrin monomer were all increased. Treatment with BAY x 4620 produced a dose-dependent attenuation of these effects with complete blockade of the hypotension as well as the observed biochemical changes at the highest dose (360 mg). In a second study, two groups of pigs were given either DXS alone or DXS plus Hoe-140. DXS-induced hypotension was completely blocked by Hoe-140 pretreatment; however, kininogen was again depleted. We conclude, therefore, that DXS-induced hypotension is produced by activation of plasma kallikrein that results in the production of bradykinin and that liberation of bradykinin and its action on B2 receptors in the vasculature are both necessary and sufficient to produce the observed effects on circulatory pressure.

Animals↗
PubMed1993

Influence of desmopressin acetate on homologous blood requirements in cardiac surgical patients pretreated with aspirin.

Conflicting results have been reported concerning the effect of the synthetic vasopressin analog desmopressin acetate (DDAVP) on perioperative bleeding and homologous blood requirements in cardiac surgery. Because patients preoperatively treated with platelet-inhibiting drugs are at increased risk of perioperative bleeding, the blood-saving effect of DDAVP was investigated in 40 male patients undergoing primary myocardial revascularization. All patients had taken aspirin within the last 5 days prior to surgery. In a double-blind, randomized trial, the effects of DDAVP (0.3 microgram/kg of body weight) were compared to those of saline placebo on postoperative blood loss and the need to replace blood products. To evaluate the drug's influence on the coagulation and fibrinolytic systems, von Willebrand factor (vWF), the activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI 1), and the split products of cross-linked fibrin (D-dimers) were investigated. The total homologous blood requirement was significantly lower in DDAVP recipients (median 2, range, 0 to 5 U) compared to placebo (median 3.5, range, 0 to 8 U; P < 0.05). Although at all points of measurement (intraoperative and postoperative) transfusion requirement was less in the DDAVP group, hematocrit values of these patients always exceeded those of the placebo group, this difference being significant at the end of the operation. Because no difference in postoperative blood loss was found, the markedly reduced transfusion requirement of the DDAVP-treated patients is explained either by reduced intraoperative bleeding or by a reduced hematocrit of the chest-tube blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗
PubMed1993

Inhibition of plasma kallikrein with aprotinin in porcine endotoxin shock.

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 micrograms/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 mumol, was given IV during 8 hours, resulting in plasma levels above 10 mumol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock.

Animals↗
PubMed1993

Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations.

The effect of high-dose aprotinin treatment on hemostatic activation during cardiopulmonary bypass in pediatric patients having cardiac operations was investigated. Sixty patients weighing less than 10 kg undergoing cardiac operations for different types of congenital heart diseases were studied: 20 patients were treated with aprotinin 2 x 15,000 KIU/kg, 20 patients with 2 x 30,000 KIU/kg, and 20 patients without aprotinin treatment served as the control group. Different split products of fibrinogen and/or fibrin and the fibrinolytic activity on fibrin plates were measured to assess fibrinolytic activation. F1/F2 prothrombin fragments, thrombin-antithrombin III-complex, and fibrin monomers were measured to estimate thrombin activation. There was a significant dose-dependent reduction in fibrin-fibrinogen split product formation during cardiopulmonary bypass: In the high-dose aprotinin group the concentration of the split products at the end of bypass was 1.5 +/- 0.6 micrograms/ml, compared with 3.4 +/- 3.0 micrograms/ml in the low-dose aprotinin group and 6.7 +/- 3.5 micrograms/ml in the control group (p < 00.5). Fibrinolytic activation on fibrin plates was also significantly reduced by aprotinin. Fibrin monomer formation was significantly diminished at the end of cardiopulmonary bypass in the high-dose group: 9.2 +/- 5.2 micrograms/ml compared with 21.6 +/- 14 micrograms/ml in the control group (p < 00.5). Elastase in complex with alpha 1-protease inhibitor at the end of bypass was increased to the same amount in the three groups: 784 +/- 278 ng/mL (control group), 693 +/- 189 ng/ml (low-dose aprotinin), and 719 +/- 270 ng/mL (high dose aprotinin) (no significant difference). Blood loss 6 hours postoperatively was significantly (p < 00.5) less in the high-dose group (99 +/- 32 ml/m2) than in the control group (164 +/- 87 ml/m2; low-dose group: 160 +/- 106 ml/m2). These observations suggest an attenuation of hemostatic activation during cardiopulmonary bypass with less plasmin formation and, because of inhibition of contact activation, less thrombin generation with aprotinin treatment. Thus the thrombotic-thrombolytic equilibrium is kept more balanced after cardiopulmonary bypass. High-dose aprotinin treatment is recommended for pediatric patients undergoing cardiac operations.

Antithrombin III↗
PubMed1993

[Prevention of thromboembolism with drugs].

Prophylaxis of thrombosis during and after surgery reduces the incidence of deep vein thrombosis and lung embolism in patients at risk. The kind of therapy applied is related to the individual risk of each patient. Antithrombotic stockings together with low-dose heparin or dextran, is recommended in low-risk patients. Alternatively intermittent pneumatic compression can be applied in these patients. In patients at high risk (hip or knee surgery) a prophylaxis regimen that has been proven efficient in this patient group must be used. Unfractionated and low-molecular-weight heparin (both also in combination with DHE), dextran and oral anticoagulants have been shown to be effective, but LMW heparin seems to be the best. Prophylaxis of thrombosis is also recommended in outpatients whose lower extremities are immobilized. The initiation of therapy, choice of medicament duration of therapy is ultimately the decision of the responsible physician, who must consider it for each individual patient.

Anticoagulants↗
PubMed1993

Sensitive detection of the activation state of blood coagulation in porcine DIC models by a new fibrin immunoassay.

Elevated levels of soluble fibrin in plasma indicate that thrombin converts fibrinogen to fibrin without sufficient inhibitory control. Therefore, measurement of soluble fibrin (SF) in plasma may be considered as a laboratory test for intravascular coagulation. We have demonstrated that a new immunoassay for detection of SF in human plasma (Lill et al., Blood Coag Fibrinol 1993; 4: 97-102), based on a fibrin specific monoclonal antibody, also detects porcine SF with high sensitivity. Thrombin-dependent generation of SF in porcine plasma in vitro resulted in increased reactivity of the assay system, which was time and dose dependent. Dextran sulphate (DXS) and bacterial lipopolysaccharide (LPS) were used as stimuli in in vivo experiments in pigs. Plasma levels of SF increased steadily after intravenous administration of DXS (5 mg/kg for 1 h) to 38 +/- 7.8 micrograms/ml (mean +/- SEM) at 2 h, whereas LPS (2 micrograms/kg/h for 6 h) markedly increased plasma SF levels to over 120 micrograms/ml (at 6 h) after a lag phase of 2 h. In conclusion, this new immunoassay for human fibrin allows specific and sensitive detection of soluble fibrin in porcine plasma.

Animals↗
PubMed1993

A new immunoassay for soluble fibrin enables a more sensitive detection of the activation state of blood coagulation in vivo.

A novel sandwich immunoassay for measurement of soluble fibrin in plasma has been developed. For immunization we used the synthetic heptapeptide Gly-Pro-Arg-Val-Val-Glu-Arg representing the amino terminus of the alpha-chain of human fibrin. A monoclonal IgG1 antibody was obtained by conventional hybridoma technology. To increase convenience, the sandwich immunoassay was developed for the Enzymun-Test systems which are based on streptavidin pre-coated tubes. The new assay was designed with the same fibrin specific antibody both in biotinylated and in peroxidase-labelled form. Fibrin in native plasma samples could only be detected after pre-incubation of the plasma with chaotropic ions. Test results were calculated using a standard curve comprising six fibrin standards (0-50 micrograms/ml). Precision of the method was satisfactory; intra-assay CVs using plasma samples ranged between 5.0% (23.7 micrograms/ml) and 12.4% (0.2 microgram/ml). CVs of interassay precision measurements using standards as samples range between 7.3% (25.0 micrograms/ml) and 11.4% (1.0 micrograms/ml). The lower detection limit was 0.12 microgram/ml. Investigations of normal range in 70 age-matched healthy individuals resulted in a mean of 1.12 micrograms/ml. Linearity was excellent; recovery of high fibrin plasma after dilution with normal plasma was always between 100 and 107%. Fibrin specificity was due to the monoclonal antibody 2B5 used and no cross reactivity with fibrinogen, fibrinogen split products or fibrin D-dimer was observed. Fibrin fragment E1 (studied by Dempfle CE, et al. Blood Coag Fibrinol 1993; 4: 79-86) and fragments X and Y showed moderate cross reactivity in the assay and caused some overestimation of fibrin at high fibrin split product concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

[Venous thrombosis following severe multiple trauma].

The incidence of thromboembolic complications in patients with multiple injuries was reviewed as well with respect to our own prospective investigation (141 patients with a mean injury severity score of 37 points). The rate of deep venous thrombosis (DVT) in severely injured patients is reported to vary from 20 to 90% if invasive diagnostic procedures are used, whereas the rate of clinically relevant manifestations of DVT seems to be much lower. Although 96% of the patient population in our study were thought to be at high risk of having DVT (applying generally accepted risk factors), only 1.4% of the subjects actually developed clinically relevant DVT. The analysis of several parameters of the coagulation and fibrinolytic systems (platelet count, prothrombin time, partial thromboplastin time, antithrombin III, prothrombin, plasminogen, tissue-plasminogen-activator and its inhibitor) showed simultaneous activation of both systems in these severely injured patients. Thus, increased coagulation seems to be counteracted by increased fibrinolysis. In addition, fluid resuscitation with crystalloid and colloid infusions in the prehospital period (1970 ml and 573 ml, respectively) can be viewed as early prophylaxis of thromboembolic complications. Thus, the low DVT rate in a high-risk patient group with multiple injuries might be at least partially explained.

Adult↗
PubMed1993

Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate.

BACKGROUND AND DESIGN--Protein C is a vitamin K-dependent plasma protein that is converted to the serine protease activated protein C by the thrombin-thrombomodulin complex. Activated protein C functions as a natural anticoagulant by inactivating the cofactors of the coagulation cascade, factors Va and VIIIa. Coumarin (warfarin)-induced skin necrosis is thought to be due to a rapid elimination of protein C relative to other vitamin K-dependent factors during the initial phase of oral anticoagulation. We have used a highly purified protein C concentrate to treat a patient with acquired protein C deficiency who developed skin necrosis during the initial phase of oral anticoagulant therapy. OBSERVATIONS AND CONCLUSIONS--During protein C concentrate therapy, no further skin lesions appeared, and the healing process of necrotic areas was facilitated. Replacement therapy with protein C concentrate appears to be safe and effective as an adjunctive treatment for coumarin-induced skin necrosis.

Aged↗
PubMed1992

Anticardiolipin antibodies and lupus anticoagulant in patients treated with different methods of renal replacement therapy in comparison to patients with systemic lupus erythematosus.

Antiphospholipid antibodies were found to be associated with certain clinical manifestations such as recurrent venous thrombosis or arterial occlusions in a wide spectrum of immune disorders [6]. We analyzed the plasma concentration of two isotypes (IgG, IgM) of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) activity in 84 patients with end-stage renal disease. They were receiving different types of renal replacement therapy and had a high frequency of thrombotic vascular complications. The prevalence of positive tests and the mean ACA concentration obtained in the plasma of renal patients were compared with those in patients with systemic lupus erythematosus (SLE) and in healthy controls. When analyzed as a whole group, renal patients maintained on dialysis (n = 45: hemodialysis, n = 20; peritoneal dialysis) or with a functioning kidney transplant (n = 19) did not differ in mean ACA concentration and LAC activity (n = 84, ACA: IgG 10 +/- 7 U/ml, IgM 2 +/- 1 U/ml, LAC ratio: 1.0 +/- 0.2) from healthy subjects (n = 50, ACA: IgG 10 +/- 3, IgM 2 +/- 1 U/ml, LAC ratio: 1.0 +/- 0.1) but they had a higher incidence of raised IgG-ACA titers (renal replacement 14% vs. normal controls 4%, p less than 0.05). No significant correlation was found between thrombotic events and raised ACA or LAC activity in dialysis patients. In contrast, the proportion of SLE patients (n = 51) with a raised concentration of ACA was significantly higher (IgG: 69%, IgM: 29%) than that among patients with renal replacement therapy (IgG: 14%, IgM: 4%) or normal controls (IgG: 4%, IgM: 2%, p less than 0.002). Moreover, recurrent manifestations of thrombosis in SLE were associated with very high IgG-ACA (n = 11, IgG 117 +/- 91 U/ml) and LAC activity (LAC ratio: 2.4 +/- 0.7) in comparison to SLE patients without thrombotic events (n = 40, ACA: IgG 23 +/- 13). The results of our investigations demonstrate that the pathogenetic role of these phospholipid antibodies in end-stage renal disease is far from established.

Adult↗
PubMed1992

Effects of protease inhibitors in experimental septic shock.

Endotoxin shock and contact system activation were used to study effects of hirudin, antithrombin III, eglin C, aprotinin, and [Arg15]-aprotinin in anesthetized pigs. Alterations in the systemic and pulmonary circulation were in part prevented by administration of the inhibitors.

Animals↗
PubMed1992

[Biochemical factors as objective parameters for assessing the prognosis in polytrauma].

One hundred patients with multiple injuries (mean ISS 37 patients) were prospectively evaluated over a period of 14 days following trauma. Significant differences in the blood levels of PMN elastase, cathepsin B, lactate, neopterin, C-reactive protein (CRP) and antithrombin III (ATIII) were found in non-survivors and in survivors with and without organ failure. On admission, a prediction of organ failure was possible with an accuracy of 63% to 69% (PMN elastase, cathepsin B, ATIII). Death was predictable with an 80% to 90% accuracy within the first 4 days (PMN elastase, lactate, CRP, neopterin). The prognostic value of these factors was comparable to trauma scores regarding organ failure and better with respect to death. Biochemical parameters may be helpful in estimating the severity of the injury and prognosis and in monitoring the ICU course of such patients.

Acute-Phase Proteins↗